Stereoconvergent [1,2]- and [1,4]-wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans: A tale of steric Vs electronic regiocontrol of divergent pathways

Article

pubs.acs.org/joc

Stereoconvergent [1,2]- and [1,4]-Wittig Rearrangements of 2‑Silyl-6-

aryl-5,6-dihydropyrans: A Tale of Steric vs Electronic Regiocontrol of

Divergent Pathways

Luis M. Mori-Quiroz and Robert E. Maleczka, Jr.*

Department of Chemistry, Michigan State University, 578 South Shaw Lane, East Lansing, Michigan 48824, United States

S

* Supporting Information

ABSTRACT: The regiodivergent ring contraction of diaste-

reomeric 2-silyl-5,6-dihydro-6-aryl-(2H)-pyrans via [1,2]- and

[1,4]-Wittig rearrangements to the corresponding α-silylcyclo-

pentenols or (α-cyclopropyl)acylsilanes favor the [1,4]-path-

way by ortho and para directing groups in the aromatic

appendage and/or by sterically demanding silyl groups. The

[1,2]-pathway is dominant with meta directing or electron-

poor aromatic moieties. Exclusive [1,2]-Wittig rearrangements are observed when oleﬁn substituents proximal to the silyl are

present. cis and trans diastereomers exhibit diﬀerent reactivities, but converge to a single [1,2]- or [1,4]-Wittig product with high

diastereoselectivity and yield.

a narrower range of substrates are capable of eﬃcient [1,2]-

migration, perhaps a reﬂection of the requisite radical-

stabilizing groups (i.e., R in Scheme 1) for facile C−O bond

homolysis. Another complication is the inherent “problem” of

regioselectivity that arises in (alkoxyallyl)metal species (A in

Scheme 1), where the [1,4]-migration competes with the [1,2]-

shift, leading to mixtures of products.^5,6Relative to the [2,3]-

and [1,2]-shifts, [1,4]-Wittig rearrangements (routes c and d)

are unique in their ability to generate stereodeﬁned enolates⁷⁻⁹

(rather than alkyl alkoxides). In addition, [1,4]-Wittig rearrange-

ments have the potential to transfer chirality and stereos-

electively form adjacent chiral centers. Although there is some

evidence supporting a stepwise mechanism for the [1,4]-pathway

(route c),^9,10a concerted process is allowed by orbital symmetry

(route d) and might be operative in some instances. As such, the

underlying factors that govern regiocontrol in favor of either the

[1,4]- or [1,2]-pathway remain unclear.^8,11−13In general, the

[1,4]-shift is favored at lower temperatures, while the nature of

the base and base counterion can aﬀect the product distribution.

However, the [1,4]:[1,2]-selectivity seems to be mostly substrate-

dependent, and few studies have attempted to uncover features

within a substrate type that can drive the rearrangement down one

path over the other.^9,14

INTRODUCTION

■

Since their discovery more than 70 years ago,¹Wittig

rearrangements have evolved into powerful tools for the

isomerization of α-metalated ethers into alkoxides. Wittig

rearrangements can proceed through a concerted, orbital-

symmetry-allowed [2,3]-sigmatropic shift (Scheme 1, route a),^2,3

Scheme 1. Possible Wittig Rearrangement Pathways of an

Allylic Ether

Although the ring contractions of macrocyclic ethers by

means of Wittig rearrangements via [1,2]- and [2,3]-pathways

have been documented in the work of Marshall¹⁵⁻¹⁷and

Takahashi,¹⁸⁻²²the behavior of smaller cyclic ethers is limited

to only a few examples explored in the course of mechanistic

studies.^8,23−27Although certain dihydrothiopyrans have been

shown to isomerize to the corresponding cyclopropyl thio-

enolates under basic conditions at low temperatures,²⁸⁻³³we

or a stepwise [1,2]-migration involving a radical/radical anion

pair (route b).⁴Arguably, the [2,3]-Wittig rearrangement

pathway has enjoyed more attention from both mechanistic and

synthetic perspectives, resulting in an impressive display of

applications such as the stereoselective assembly of adjacent

chiral centers, the transfer of chirality, and the formation of

oleﬁns with speciﬁc geometries.^2,3Although some of these fea-

tures are also characteristics of the [1,2]-Wittig rearrangement,

Received: December 2, 2014

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are aware of only two [1,4]-Wittig rearrangements of cyclic

allylic ethers. Reported by Rautenstrauch in 1972, these

examples involve the isomerization of dihydropyran and nerol

oxide to the corresponding α-cyclopropylacetaldehydes

(Scheme 2).⁸Surprisingly, these rearrangements did not receive

RESULTS AND DISCUSSION

■

Synthesis of 2-Silyl-5,6-dihydro-6-aryl-(2H)-pyrans

and Precursors. Benzylic trichloroacetimidates S1 were

prepared by addition of homoallylic alcohols to trichloroace-

tonitrile under basic conditions (Scheme 3). α-Hydroxysilanes

S2 were prepared by retro-Brook rearrangement of in situ

generated O-silylated allylic alcohols. The preparation of

O-trimethylsilyl α-hydroxysilanes S2-f and S2-g involved

trapping of the corresponding alkoxides with (TMS)Cl prior

to aqueous workup (Scheme 3).

Scheme 2. Wittig Rearrangements of Dihydropyrans

Lewis acid-catalyzed etheriﬁcation of α-hydroxysilanes S2

with benzylic trichloroacetimidates S1 provided diastereomeric

dienes S3 that were submitted to ring-closing metathesis to

aﬀord cyclic ethers 1 and 2 (Scheme 4). Without exception,

diastereomeric producs 1 (trans) and 2 (cis) were completely

separated by column chromatography, although in some cases

these could be prepared from diastereomerically pure pre-

cursors syn- or anti-S3. The alternative preparation of some

dienes S3 is shown in Scheme 5. Compounds S3-j and S3-x

were synthesized by a three-component condensation of

allyltrimethylsilane, a benzaldehyde derivative and O-trimethyl-

silyl α-hydroxysilane S2-f or S2-g, whereas dienes S3-k were

prepared by Suzuki cross-coupling of precursors S3-cc with

phenylboronic acid (Scheme 5).

Behavior of Model Substrates. Our group recently

reported the highly selective [1,4]-Wittig rearrangement of

allyl benzyl ether bearing a trimethylsilyl group at the α-allylic

position.^13,52Given the ability of the silyl group to (1) allow a

selective deprotonation⁵³⁻⁵⁶step and (2) suppress the com-

petitive [1,2]-pathway, we envisioned that diastereomeric cyclic

ethers 1a/2a (trans and cis, respectively) would be suitable

substrates for Wittig rearrangements (Scheme 6). Indeed,

under optimized conditions⁵⁷(THF, −78 °C), the trans dia-

stereomer 1a underwent fast and selective allylic deprotonation

by n-butyllithium and rearrangement within 5 min to give a

mixture of the trans [1,4]-Wittig (α-cyclopropyl)acylsilanes 3a

and cis [1,2]-Wittig α-silylcyclopentenol 4a in good overall

yield (82%), albeit with modest selectivity (∼2.4:1) in favor of

the [1,4]-product. Remarkably, the diastereoselectivity of both

[1,4]- and [1,2]-products was excellent. On the other hand, cis

diastereomer 2a was signiﬁcantly less reactive and required

excess s-butyllithium for complete conversion in 3 h. To our

surprise, the same major diastereomers for both the corre-

sponding [1,4]-shift (3a) and [1,2]-shift (4a) were obtained in

further attention despite being complementary to Simmons−

Smith-type reactions,³⁴⁻³⁶transition-metal-catalyzed diazoalkyl

decomposition/oleﬁn insertions,³⁷⁻⁴²and intramolecular cycli-

zations,⁴³⁻⁴⁶cycloisomerizations,⁴⁷⁻⁵⁰or stepwise cyclopropa-

nation reactions.⁵¹

In this paper we demonstrate that the regioselection in favor

of the [1,4]- or [1,2]-pathway within the context of the Wittig

rearrangements of diastereomeric 2-silyl-6-aryl-5,6-dihydro-

(2H)-pyrans (Scheme 2) is dependent on both electronic

and steric factors. Thus, through electronic “tuning” at the

aromatic appendage, judicious choice of the silyl group, or

selecting certain oleﬁn substitution patterns, allows one to

maneuver these ring contractions toward α-silylcyclopentenols

(via [1.2]-Wittig) or (α-cyclopropyl)acylsilanes (via [1,4]-

Wittig), with excellent diastereoselectivities and in a stereo-

convergent fashion.

Scheme 3. Synthesis of Precursors S1 and S2

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Scheme 4. Synthesis of Dienes S3 and Silyl Cyclic Ethers 1

and 2

Scheme 6. [1,2]- and [1,4]-Wittig Rearrangements of Model

2-Silyldihydropyrans 1a and 2a under Optimized Conditions

Electronic Eﬀects. Our study continued with the evaluation

of the electronic eﬀects on the aromatic appendage (Table 1).

Such modiﬁcations to pyrans 1a and 2a were expected to

directly impact the ability of the benzylic carbon to migrate

through a [1,4]- or [1,2]-mode. Nonetheless, the same reac-

tivity trend was observed for these compounds: trans dia-

stereomers 1b−l (entries 1−11) underwent complete rear-

rangement within 10 min, whereas cis diastereomers 2b−l

(entries 12−22) required at least 3 h for complete conversion.

A second trend was clearly observed in the trans dia-

stereomers series: Electron-donating groups located at the ortho

and para positions increased the [1,4]-selectivity (entries 3, 4,

and 6), with the p-methoxy-substituted compound 1d giving

exclusive [1,4]-selectivity. o-Methoxy substrate 1b (entry 1) is

an exception that might be attributed to coordination of oxygen

lone pairs to the lithium cation during rearrangement, leading

to a slight decrease in [1,4]:[1,2]-selectivity relative to that of

the unsubstituted analogue 1a. The inductively electron-

withdrawing methoxy group located at the meta position

(entry 2) led to an evident decrease in [1,4]:[1,2]-selectivity,

providing the [1,2]-Wittig product in slight excess over the

[1,4]-product. The weakly electron-donating methyl group

located at the meta position (entry 5) led to a negligible eﬀect

in product distribution relative to that of the model substrate

1a. The ﬁne balance between resonance and inductive eﬀects

was even more evident in halogenated compounds (entries 7

and 8): p-Fluoro-substituted compound 1h aﬀorded a 6:1

[1,4]:[1,2]-selectivity, whereas p-chloro-substituted compound

1i gave the reverse regioselection ([1,4]:[1,2] = 1:1.5). On the

opposite side of the spectrum, a p-triﬂuoromethyl group at the

phenyl ring led to exclusive formation of the [1,2]-Wittig

product (entry 9), whereas a p-biphenyl and 2-naphthyl groups

directly attached to the migrating carbon also aﬀorded high

selectivity in favor of the [1,2]-shift (entries 10 and 11). In all

pertinent cases, the [1,2]-Wittig product was obtained as a

single diastereomer, whereas the [1,4]-product was formed with

high diastereoselection (>15:1).

a

Values in parentheses refer to the yield of a mixture of diastereomers

1 and 2 prepared from the corresponding mixture of syn/anti

precursors S3. See the Experimental Section for diastereomeric ratios.

Scheme 5. Alternative Synthesis of Dienes S3

Evaluation of cis diastereomers (entries 12−22, Table 1)

conﬁrmed the stereoconvergence of the [1,4]- and [1,2]-Wittig

rearrangements. Both [1,4]- and [1,2]-pathways proceeded

with diastereoselectivity similar to that of their trans counter-

parts, and the same electronic eﬀects in product distribution

were observed in most cases. The sluggishness of cis dia-

stereomers to undergo allylic deprotonation had a detrimental

eﬀect on the overall yield due to competitive reactions such

as ortho metalation (entries 14 and 18), lithium−halogen

exchange (entry 19), and presumably competitive benzylic

deprotonation (entry 20). Competitive ortho metalation, in

particular, seems to retard rearrangement signiﬁcantly, as

suggested by deuterium quenching experiments.⁵⁸

virtually the same [1,4]:[1,2] regioisomeric ratio (∼2:1)

observed for the trans isomer and in good overall yield.

The full stereoconvergence in the [1,2]- and [1,4]-Wittig

rearrangements of trans (1a) and cis (2a) diastereomers is of

signiﬁcant importance because, in particular for the [1,2]-Wittig

pathway, it challenges the known stereochemical outcome of

this manifold.⁴However, this apparent conﬂict can be rational-

ized by invoking the intermediacy of a common intermediate,

and we have gathered supporting evidence of such species (vide

infra) that accounts for the observed stereoconvergence and the

similar product ratios obtained from the isomerization of each

diastereomer.

C

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Table 1. Electronic Eﬀects on the [1,2]:[1,4]-Product Distribution

a

b

c

bd

,

entry

substrate

Ar

conditions

[1,4] yield (%)

[1,4] dr

[1,2] yield (%)

[1,4]:[1,2] ratio

1

2

3

4

5

6

7

1b

1c

1d

1e

1f

2-MeOC₆H₄

3-MeOC₆H₄

4-MeOC₆H₄

2-MeC₆H₄

3-MeC₆H₄

4-MeC₆H₄

4-FC₆H₄

A

B

56

33

65

80

59

86

66

28

trace

4

15:1

17:1

15:1

20:1

15:1

37

44

1.5:1.0

1.0:1.3

>98.5:1.0

5.3:1.0

15

30

7

2.0:1.0

1g

1h

1i

12.3:1.0

6.0:1.0

11

65

80

59

96

34

25

e

8

4-ClC₆H₄

4-CF₃C₆H₄

4-PhC₆H₄

2-Naph

1.0:2.3

9

10

11

12

13

1j

<1.0:98.5

1.0:14.8

1.0:32.0

1.5:1.0

1k

1l

nd

3

nd

2b

2c

2d

2e

2f

2-MeOC₆H₄

3-MeOC₆H₄

4-MeOC₆H₄

2-MeC₆H₄

3-MeC₆H₄

4-MeC₆H₄

4-FC₆H₄

50

33

52

69

51

73

25

nd

7

15:1

18:1

8:1

1.3:1.0

f

14

>98.5:1.0

5.8:1.0

15

16

17

20:1

10:1

nd

12

20

7

2.6:1.0

2g

2h

2i

10.4:1.0

8.3:1.0

g

18

3

h

19

4-ClC₆H₄

4-CF₃C₆H₄

4-PhC₆H₄

2-Naph

nd

12

75

59

h

20

2j

>1.0:98.5

1.0:10.7

21

2k

7:1

nd

i

22

2l

<4

1.0:14.8

a

b

c

d

Conditions: (A) n-BuLi (1.2 equiv), 10 min; (B) s-BuLi (3 equiv), 3 h. Isolated yields. Determined by ¹H NMR of isolated material. dr > 20:1 in

e

f

g

h

all cases. A 1.1 equiv amount of n-BuLi. At −78 °C, 6 h, then rt, 20 h. Total of 58% recovered 2h and isomeric enol cyclic ether. Complex

mixture. Time 6 h.

i

We conducted a Hammett plot analysis for para-substituted

compounds (X = MeO, Me, F, Cl, and CF₃) in the trans series

(Table 1, entries 3 and 6−9) because these diastereomers

underwent clean rearrangement relative to their cis counter-

parts. Since the [1,2]-Wittig rearrangement is believed to follow

a stepwise mechanism and assuming the [1,4]-shift proceeds by

an analogous homolytic process, both would be dependent on

the extent of radical stabilization at the migrating center.

Therefore, we initially attempted to correlate σ^•scales vs

log(k_X/k₀) (where k_X= [1,2]:[1,4] ratio derived from para-

substituted compounds and k₀= [1,2]:[1,4] ratio from 1a);

however, severe deviations from linearity were obtained. On the

other hand, good correlation of our data with σ and σ⁺

parameters was obtained (R²> 0.96) (Figure 1). This suggests

that spin delocalization of a presumed benzylic radical is not as

important as the polar eﬀects induced by the para substituents

Figure 1. Hammett plots of log(k_X/k₀) vs σ and σ⁺.

in the transition state of C−O bond cleavage, which is likely the

rate-determining step.⁵⁹A buildup of negative charge at the

benzylic migrating carbon appears to favor the [1,2]-migration,

whereas any increasingly positive character of this position

favors the [1,4]-shift. The large ρ values (3.10 and 4.37)

indicate a high sensitivity to the nature of the substituent X,

and a balance between resonance and inductive eﬀects seems

to play an important role in determining the [1,4]:[1,2]-

selectivity. We cautiously interpret these observations as

supporting evidence for a stepwise mechanism for both [1,2]-

and [1,4]-pathways, in which a relatively slow C−O bond

homolysis is followed by rapid intramolecular recombination of

the diradical anion, leading to the observed products.

Discarding a Background Isomerization Pathway. We

were cognizant of the possibility that the [1,2]-Wittig alkoxide

and [1,4]-Wittig enolate (that is, the primary rearrangement

products) might equilibrate prior to workup, giving a false

“electronic eﬀect”. In fact, α-cyclopropyl ketones bearing anion-

stabilizing groups attached to the ring are known to undergo

ring expansion to their cyclopentenol isomers under basic

D

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conditions,⁶⁰whereas some cyclopropyl thioenolates isomerize

to the corresponding cyclopentenyl thiolates.^32,33However,

independent subjection of selected products to the reaction

conditions A or B (Table 1) did not lead to any [1,2]/[1,4]-

interconversion (or vice versa) (Scheme 7). In line with this

Table 2. Eﬀect of the Silyl Group on the [1,2]:[1,4]-

Selectivity

a

Scheme 7. Isomerization of the [1,4]-Enolate to the [1,2]-

Alkoxide (and Vice Versa) Was Not Observed

[1,4]

yield

(%)

[1,2]

bd

,

b

[1,4]

c

yield

(%)

[1,4]:[1,2]

ratio

entry substrate

SiR₃

dr

1

2

3

4

5

1a

SiMe₃

58

69

79

93

60

74

51

71

15:1

20:1

10:1

24

7

2.4:1.0

1m

1n

1o

2a

SiMe₂Ph

SiMePh₂

SiEt₃

9.9:1.0

>98.5:1.0

18.6:1.0

2.1:1.0

5

29

7

SiMe₃

6

2m

2n

2o

SiMe₂Ph

SiMePh₂

SiEt₃

10.6:1.0

>98.5:1.0

17.8:1.0

e

7

f

8

4

a

Conditions: (A) n-BuLi (1.2 equiv), 10 min; (B) s-BuLi (3 equiv), 3 h.

b

c

d

1

Isolated yields. Determined by H NMR of isolated material. dr >

e

f

20:1 in all cases. Total of 16% recovered 2n. At −78 to 0 °C, 6 h.

observation, the diastereoselectivity in both [1,4]- and [1,2]-

ring contractions is deﬁned during rearrangement, as little or no

change in diastereomeric ratio was observed in these control

experiments. In fact, only upon warming the reaction mixture of

certain [1,2]-products (alkoxides) for prolonged periods was

epimerization ever observed. Thus, we have established that the

observed product ratios are a true consequence of electronic

eﬀects and a secondary equilibration pathway is not operative at

−78 °C.⁶¹

Stereoelectronic Eﬀects of the Silyl Group. We next

looked to tackle the modest [1,4]:[1,2]-selectivity obtained in

most cases, as well as the adverse [1,4]-selectivity in electron-

deﬁcient substrates. A closer inspection of the [1,2]-Wittig

product reveals two adjacent stereocenters in which the bulkier

groups (Ph and SiMe₃) are in a cis relationship. Since the [1,2]-

Wittig pathway proceeds via a radical/radical anion inter-

mediate (Scheme 8),⁴we rationalized that increasing the steric

increasing the bulkiness of the silyl group only with alkyl groups

(SiEt₃, entry 4) also led to excellent [1,4]:[1,2]-selectivity.

The corresponding cis diastereomers aﬀorded virtually the

same product ratios with excellent diastereoselectivities.

However, the more sterically demanding silyl groups were

deleterious for the reactivity of these isomers. Given that the

reactivity of trans isomers was minimally aﬀected, the severe

loss of reactivity in cis diastereomers suggests bulkier silyl

groups shift the conformational equilibrium to the less reactive

conformation. The relevant conformers for both trans and cis

diastereomers involve half-chair arrangements and are depicted

in Scheme 9. Although the system in discussion involves a

Scheme 9. Conformational Analysis for the trans (1) and cis

(2) Diastereomers Relevant for the Deprotonation Step

Scheme 8. Diradical Anion Species Leading to Alkoxide

Products by Intramolecular Recombination ([1,2]-Product)

demand of the silyl (SiR₃) group would inhibit recombina-

tion via the [1,2]-pathway, indirectly stimulating the [1,4]-

migration.

dihydropyran structure, we believe it is reasonable to use A

values (derived from the cyclohexane system) to estimate

conformational ratios since the overall trend should remain.

Accordingly, in the case of trans diastereomer 1, conformers

I and II are expected to exist in approximately a 1:2.5 ratio,

with a small predominance of conformer II on the basis of the

conformational A values for trimethylsilyl and phenyl groups in

cyclohexane (2.5 and 2.9, respectively).^62,63

Gratifyingly, our hypothesis was right, and a gradual increase

in the steric demand of the silyl group consistently led to

greater [1,4]:[1,2]-product ratios (Table 2). In the trans series,

changing a SiMe₃group to a SiMe₂Ph group increased the

selectivity from 2.4:1 to ∼10:1 (entries 1 and 2), and the even

larger SiMePh₂group facilitated exclusive [1,4]-Wittig rear-

rangement in excellent yield (entry 3). We believe the

improved regioselectivity is primarily dominated by the sterics

of the silyl group with little electronic contribution. Indeed,

As we have previously suggested in the case of α-silyl acyclic

ethers,¹⁴we believe the optimum conformation for allylic

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deprotonation requires an antiperiplanar arrangement of the

allylic C−H and benzylic C−O bonds,^64,65which presumably

heightens the acidity of the allylic C−H bond.⁶⁶In addition, the

resulting pseudoequatorial carbanion is expected to be more

stable than the axial one, as suggested by theoretical^67,68and

experimental^26,69−73studies. Conformer II, in which the aryl

ring is orientated pseudoequatorially and the silyl group pseu-

doaxially, meets this requirement. Although an increase in the

steric demand of the silyl group is expected to shift the con-

formational equilibrium to the less reactive conformer I, the

extent of this perturbation is expected to be modest given the

larger Si−C bond length (1.89 Å vs 1.54 Å for C−C bonds)

and the absence of severe steric interactions of the pseudoaxial

silyl group in conformer II. On the other hand, cis diaste-

reomers 2 are intrinsically “locked” in conformation IV in

which both aryl and silyl groups are oriented in pseudoequa-

torial positions. The required conformation for deprotonation

(conformation III) presents a severe steric clash between these

bulky groups, which is expected to get worse as the silyl group

becomes more sterically demanding.

Because the conformational equilibrium was also expected

to be dependent on the steric demand of the aryl group, we

reasoned that installing a large ortho substituent would lead to

an increase in the population of conformers II and IV (for the

trans-1 and cis-2 diastereomers, respectively), leading to a

further increase of reactivity of the trans diastereomer (1) and a

decrease in the reactivity of the cis diastereomer (2). Consistent

with this hypothesis is the observation that placement of a

propyl group at the ortho position of the phenyl ring did not

inﬂuence the reactivity of 1s (full conversion in <10 min as

observed with 1a), whereas 2s reacted more slowly than the

unsubstituted 2a (only 63% conversion in 3 h vs full conversion

in the case of 2a) (Scheme 10).

biased toward the [1,2]-Wittig rearrangement and studied the

eﬀect of silyl groups larger than SiMe₃, which were expected to

shift the selectivity in favor of the [1,4]-pathway (Table 3).

trans and cis diastereomers 1p and 2p bearing an m-methoxy

group at the phenyl ring and the bulky SiMe₂Ph underwent

rearrangement with higher [1,4]:[1,2]-selectivity (3.9:1 and

3.5:1, respectively, entries 2 and 3) relative to the SiMe₃coun-

terpart 1c (∼1:1.3, entry 1). Following this trend, in the trans-

substituted (p-chlorophenyl)dihydropyran series, the [1,4]:

[1,2]-selectivity was gradually reversed from 1:2.3 with the

SiMe₃analogue 1i (entry 4) to ∼1:1 for the bulkier SiMe₂Ph

group in 1q (entry 5) and to 2.8:1 for the SiEt₃derivative 1r

(entry 6). The trans-2-naphthyl-substituted dihydropyrans

bearing a SiMe₃(1l) and SiEt₃(1s) aﬀorded ∼1:32 and ∼1:5

[1,4]:[1,2]-selectivities (entries 7 and 8), respectively. Analysis

of the crystal structure of [1,2]-Wittig product 4s (Figure 2)

bearing the 2-naphthyl and SiEt₃groups in a cis relationship

suggests a signiﬁcant steric clash between these groups exists

and thus the [1,4]:[1,2]-selectivity is higher for 1s vs 1l.

The opposite diastereomer 2s aﬀorded a 5:1 [1,4]:[1,2]-

selectivity (entry 9). The opposite regioselectivity obtained

from diastereomers 1s and 2s is a consequence of the higher

temperature and prolonged reaction time for the rearrangement

of 2s. One possible explanation is that under these reaction

conditions the initially formed [1,2]-Wittig alkoxide isomerizes

to the corresponding [1,4]-enolate. However, we also speculate

that competitive arene metalation leads to an electron-rich spe-

cies that following allylic deprotonation rearranges preferen-

tially via the [1,4]-Wittig pathway. Although no evidence of the

intermediacy of such species was gathered in this speciﬁc case,

we have determined that doubly lithiated species (heteroaryl/

allylic dianion) rearrange with remarkably diﬀerent selectivies

relative to the monolithiated species (see below).

Eﬀect of Oleﬁn Substitution. The eﬀect of oleﬁn

substitution was studied next. Alkyl or alkenyl substitution

proximal to the silyl group veered the selectivity exclusively to

the [1,2]-Wittig rearrangement. Cyclopentenols were obtained

in good yields and excellent diastereoselectivity; however, a

noticeable decrease in reactivity was observed in both trans

and cis diastereomeric ethers, and longer reaction times were

required for complete conversion (Table 4).⁷⁴We attempted to

shift the selectivity in favor of the [1,4]-pathway by electronic

modiﬁcation of the aromatic ring (introducing para electron-

donating groups), but only the [1,2]-products were obtained,

and no cyclopropyl compounds were observed in these cases.

In contrast to the previous examples, alkyl oleﬁn substitution

distal to the silyl group provided low [1,4]:[1,2]-product selec-

tivity, but with good overall yields (Table 5). The diaste-

reoselectivity of the [1,2]-shift remained high as in previous

examples, but that of the [1,4]-product, bearing an all-carbon

quaternary center, was modest. The lower [1,4]:[1,2]-selectivity

with respect to that of unsubstituted analogues (Scheme 6)

suggests the methyl substitution slightly hinders the [1,4]-shift

due to steric reasons.

The exclusive [1,2]-selectivity observed in substrates having

oleﬁn substitution proximal to the silyl group (but not when

distal) can be attributed to an unfavorable steric interaction

between the oleﬁn substituent and the silyl group. We con-

jecture that this leads to partial localization of the allyl anion

(prior to rearrangement)^75,76or of the putative diradical anion

intermediate in a stepwise scenario (Scheme 8), leading to a

structural distortion that completely inhibits the [1,4]-Wittig

migration.

Scheme 10. Eﬀect of Increasing Steric Demand at the ortho

Position of the Aromatic Ring

Of interest is the observation that the eﬀect of increasing

the steric demand of the aryl group on product distribution is

equivalent to what was observed by changing the size of the

silyl group. In the trans series the [1,4]:[1,2] ratio gradually

increased from 2.4:1 for the unsubstituted substrate 1a to 5.3:1

for o-methyl analogue 1e and to 11:1 for o-propyl analogue 1s.

A similar increase in [1,4]:[1,2]-selectivity is observed in corre-

sponding cis diasteromers 2a (2:1), 2e (5.8:1), and 2s (8.4:1).

This is supportive of our initial hypothesis and the determining

role of sterics in the product distribution.

Outcome of Antagonistic Electronic and Steric

Properties. We also evaluated the competition between

opposite steric and electronic eﬀects as per the above discussion.

For this purpose, we chose substrates that were electronically

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a

Table 3. Competition between Electronic and Steric Eﬀects

bc

,

bc

,

entry

substrate

SiR₃

Ar

[1,4] yield (%)

[1,2] yield (%)

[1,4]:[1,2] ratio

1

2

1c

1p

2p

1i

SiMe₃

SiMe₂Ph

SiMe₃

SiMe₂Ph

SiEt₃

3-MeOC₆H₄

4-ClC₆H₄

2-Naph

33

67

49

28

47

64

3

44

17

14

65

44

23

96

75

9

1.0:1.3

3.9:1.0

3.5:1.0

1.0:2.3

1.1:1.0

2.8:1.0

1.0:32.0

1.0:4.7

5.0:1.0

d

3

4

5

6

7

8

1q

1r

1l

SiMe₃

SiEt₃

1s

2s

2-Naph

16

e

9

SiEt₃

2-Naph

45

a

b

c

Conditions: (A) n-BuLi (1.2 equiv), 10 min; (B) s-BuLi (3 equiv), 3 h. Isolated yields. See the Experimental Section for the dr of the products.

d

e

Time 6 h, 20% recovered 2p and isomeric cyclic enol ether. At −78 to 0 °C, 6 h.

through the usual allylic monoanion or through a dianionic

species generated by initial deprotonation at the heteroaryl ring

followed by allylic deprotonation. Diastereomeric 2-thiophene-yl

(1aa/2aa) and 2-furyl (1bb/2bb) cyclic ethers were subjected

to our standard reaction conditions for cis and trans diaste-

reomers (Scheme 11). The trans isomers 1aa and 1bb under-

went complete rearrangement within 10 min with signiﬁcantly

diﬀerent [1,4]:[1,2]-selectivities, revealing a high electronic

dependence. The trans-2-thiophene-yl-substituted compound

1aa aﬀorded a 3:1 [1,4]:[1,2]-product ratio in 97% overall

yield, whereas the analogous trans-2-furyl-substituted com-

pound 1bb rearranged exclusively via the [1,2]-pathway to

give cyclopentenol 4bb in 81% yield. On the contrary, the

Figure 2. Crystal structure of [1,2]-Wittig product 4s.

corresponding cis diasteromers 2aa (2-thiophene-yl) and 2bb

(2-furyl) underwent exclusive [1,4]-Wittig rearrangements to

give (cyclopropyl)acylsilanes 3aa and 3bb (>20:1 selectivity) in

84% and 48% yields (based on recovered starting material

(brsm)), respectively, both with low diastereoselectivity.

The unexpected exclusive [1,4]-Wittig selectivity in the

rearrangement of both cis diastereomers 2aa and 2bb suggested

that competitive deprotonation at the heteroaryl system was

taking place. Indeed, deuterium-trapping experiments demon-

strated the intermediacy of a dianionic species formed by

deprotonation at the 5-position of both thiophene-yl and furyl

rings and at the allylic position. Additional control experiments

discarded the potential isomerization of the [1,2]-alkoxide to

the [1,4]-enolate within the reaction time (3 h) at −78 °C. For

instance, both [1,4]-enolate and [1,2]-alkoxide products were

generated in 10 min from the rearrangement of trans-2-

thiophene-yl-substituted isomer 1aa, and the reaction mixture

was kept at −78 °C for an additional 3 h. Both [1,4]- and [1,2]-

Wittig products 3aa and 4aa were isolated in a combined

81% overall yield and in a 5:1 ratio. That is, the [1,4]:[1,2]-

selectivity was not signiﬁcantly modiﬁed, and [1,4]/[1.2]-

equilibration does not take place to a signiﬁcant extent.

Although this product ratio is slightly higher than that observed

when the reaction was stopped after 10 min, the lower yield of

the reaction suggests some product decomposition took place

during the extended time, thereby inﬂuencing the measured

product distribution.

a

Table 4. Oleﬁn Substitution Proximal to the Silyl Group

b

time

(h)

yield of 4

entry substrate

R

Ar

(%)

1

2

1u

1v

1w

1x

2u

2v

2w

2x

Me

Ph

0.5

1.5

7

85

72

91

75

79

26

75

12

4-MeOC₆H₄

4-MeC₆H₄

Ph

3

c

4

isopropenyl

Me

5

6

Ph

Me

4-MeOC₆H₄

4-MeC₆H₄

Ph

7

Me

6

d

8

isopropenyl

20

a

Conditions: (C) (1u−x) n-BuLi (1.2 equiv), 30 min; (D) (2u−x)

s-BuLi (3 equiv), 6−7 h. Isolated yields. Total of 13% recovered 1x.

b

c

d

Total of 51% recovered 2x.

[1,4]-Wittig Selectivity of Dianionic Species. We have

found that the [1,4]:[1,2]-selectivity in certain heteroaryl-

substituted substrates diverged markedly when proceeding

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a

Table 5. Oleﬁn Substitution Distal to the Silyl Group

b

entry

substrate

Ar

[1,4] yield (%)

dr

[1,2] yield (%)

dr

[1,4]:[1,2] ratio

1

2

3

4

1y

1z

2y

2z

Ph

44

42

45

7:1

9:1

6:1

5:1

38

43

32

20:1

12:1

20:1

1.2:1.0

1.0:1.0

1.3:1.0

1.5:1.0

4-MeC₆H₄

Ph

4-MeC₆H₄

30

a

b

Conditions (C) (1y, 1z) n-BuLi (1.2 equiv), 15 min; (D) (2y, 2z): s-BuLi (3 equiv), 6 h. Isolated yields.

Scheme 11. Rearrangements of Heteroaromatic Substrates

Scheme 13. Deuterium Trapping Experiments and Proposed

Origin of Stereoconvergence

Stereochemical Course of the [1,4]- and [1,2]-Wittig

Rearrangements. To ascertain the origin of stereoconver-

gence, we ﬁrst studied the rearrangement of enantiomerically

enriched substrates (−)-1a and (+)-2a (both in 76% ee)

(Scheme 12). Although the [1,2]-Wittig shift is known to occur

Scheme 12. Stereochemical Course of the [1,4]- and [1,2]-

Wittig Rearrangements of (−)-1a and (+)-2a

epimerization (dr > 20:1). On the other hand, attempts to trap

the allylic anion B derived from 2a with D₂O were unsuccessful,

suggesting such species undergoes immediate rearrangement.

On the basis of these results, we speculate the ﬂeeting

carbanion B is the actual species undergoing rearrangement,

which implies the allylic carbanion A, generated from 1a (which

can be trapped with D₂O), has to isomerize⁷⁷to species B. This

is consistent with the fact that the chiral information at the

silicon-bearing center (the allylic stereocenter) is destroyed

during both [1,2]- and [1,4]-Wittig rearrangements and the

absolute conﬁgurations of both products are determined ex-

clusively by the conﬁgurations of the migrating carbon.

It is important to note that the rearrangement of species B is

in accord with the “normal” stereochemical course at the

lithium-bearing carbon in the [1,2]-Wittig pathway (assuming a

localized character of (α-silylallyl)lithium B) involving inver-

sion of stereochemistry. Lastly, the observation that the stereo-

chemical course of the [1,4]-Wittig rearrangement in these

cyclic systems mirrors that of the competing [1,2]-migration

strongly suggests both pathways involve the same stepwise

mechanism.

with high retention of stereochemistry at the migrating carbon,

in both acyclic⁴and cyclic²⁶ethers, the stereochemical course

of the competing [1,4]-Wittig pathway has only been studied in

one acyclic instance.¹⁰As expected, [1,2]-Wittig rearrangement

of (−)-1a and (+)-2a proceeded with very high retention of

stereochemistry at the benzylic carbon to give enantiomeric

cyclopentenols (+)-4a and (−)-4a in 73% and 74% ee,

respectively. Importantly, the [1,4]-Wittig shift of (−)-1a

and (+)-2a also occurred with retention of stereochemistry at

the migrating center to give enantiomeric (α-cyclopropyl)-

acylsilanes (−)-3a and (+)-3a in 62% and 56% ee, respectively.

In separate experiments, we attempted to trap allylic carb-

anions A and B generated by deprotonation of 1a and 2a,

respectively (Scheme 13). Quenching the reaction of 1a with

D₂O immediately after n-BuLi addition (t < 1s) led to deu-

terium incorporation (20%) at the allylic position without

CONCLUSIONS

■

In summary, we have developed a method to access

(α-cyclopropyl)acylsilanes and α-silylcyclopentenol structures

with high diastereoselectivities and overall high eﬃciency via

[1,4]- and [1,2]-Wittig rearrangements of 2-silyl-6-aryldihy-

dropyrans. The regioselective allylic deprotonations that trigger

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Preparation of Trichloroacetimidates S1: General Procedure B.

To a solution of the corresponding homoallylic alcohol (16 mmol) in

dichloromethane (80 mL) was added DBU (0.18 equiv). The solution

was cooled at 0 °C, and trichloroacetonitrile (1.4 equiv) was added.

The reaction was followed by TLC (typically 5% EtOAc in hexanes)

using triethylamine-prewashed plates. After completion of the reaction

(typically 3−4 h), the reaction mixture was concentrated by rotary

evaporation, and the residue was partially puriﬁed by silica gel column

chromatography (typically 5% EtOAc in hexanes) buﬀered with ∼1%

triethylamine.

Preparation of α-Hydroxysilanes S2: General Procedure C. A

solution of the corresponding allylic alcohol in THF was cooled at

−78 °C, and n-butyllithium (1.6 M in hexanes) was added dropwise

over 5 min. After 30 min the corresponding chlorosilane was added

dropwise via syringe. After the resulting solution was stirred for 1 h,

sec-butyllithium or tert-butyllithium (see below for details) was added

dropwise over 45−60 min, and then the reaction was kept at the

indicated temperature.

Preparation of Diastereomeric Diene S3: General Procedure D.

To a solution of α-silyl allylic alcohol S2 (4 mmol, 1 equiv) in hexane

(22 mL) was added the desired trichloroacetimidate S1 (1.5−

1.9 equiv). The solution was cooled at 0 °C and 0.1 equiv of

(TMS)OTf in hexane was added dropwise. The reaction was warmed

at room temperature and monitored by TLC. Typically, formation of a

thick suspension indicated the end of the reaction. The solid was

ﬁltered through a plug of Celite and rinsed with hexanes (∼50 mL).

The ﬁltrate was extracted with NaHCO₃(satd) (3 × 20 mL), H₂O

(2 × 20 mL), and brine (20 mL) and dried over MgSO₄. After

ﬁltration and concentration, the residue was puriﬁed by column

chromatography.

Alternative Synthesis of Diastereomeric Acyclic Ethers S3:

General Procedure E. To a solution of O-trimethylsilyl α-(trimeth-

ylsilyl)allylic alcohol (10 mmol) in dichloromethane (50 mL) were

added allyltrimethylsilane (1.1 equiv) and the desired benzaldehyde

derivative (1.1 equiv). The solution was cooled at −78 °C, and

(TMS)OTf (0.2 equiv) was added dropwise. The reaction was fol-

lowed by TLC and usually required between 1 and 4 h. The reaction

was quenched by adding NaHCO₃(satd) (20 mL). The aqueous phase

was washed with dichloromethane (2 × 30 mL). Combined organic

extracts were washed with NaHCO₃(satd) (2 × 20 mL), H₂O

(20 mL), and brine (20 mL) and dried over MgSO₄. After ﬁltration

and concentration, the residue was puriﬁed by column chromatog-

raphy.

these rearrangements are made possible by the silyl appendage.

trans/cis diastereomers show markedly diﬀerent reactivities

toward the deprotonation step, which we have rationalized on

the basis of the expected acidities of equilibrating conformers.

We have shown that the [1,4]:[1,2]-selectivity is governed by

both electronic and steric characteristics of the reacting cyclic

ethers. The [1,4]-Wittig pathway is favored by increasing the

electron density at the migrating carbon and also by increasing

the steric demand of the silyl group. On the other hand,

electron-deﬁcient migrating centers favor the [1,2]-pathway,

and oleﬁn substitution at the oleﬁn proximal to the silyl group

leads to exclusive [1,2]-migration. The role of the silyl group in

determining the [1,4]:[1,2]-selectivity seems to be predom-

inantly steric; however, electronic modiﬁcation at the silyl

group substituents has not been explored in this study. Stereo-

chemical experiments demonstrate both [1,4]- and [1,2]-Wittig

rearrangements of dihydropyrans proceed with high retention

of stereochemistry at the migrating center. Deuterium-trapping

experiments support the intermediacy of a common inter-

mediate, which is responsible for the observed stereo-

convergence of both isomerization pathways. Taken together,

our results make it reasonable to conclude that the primary

mechanism of the [1,4]-Wittig migration in these cyclic ethers

involves a stepwise process analogous to the [1,2]-pathway.

Further studies to expand the scope of these transformations

are under way.

EXPERIMENTAL SECTION

■

Unless otherwise noted all reactions were run under a positive

atmosphere of nitrogen in oven-dried or ﬂame-dried round-bottom

ﬂasks or disposable drum vials capped with rubber septa. Solvents were

removed by rotary evaporation at temperatures lower than 45 °C.

Column chromatography was run on 230−400 mesh silica gel. Tetra-

hydrofuran and diethyl ether were distilled from sodium benzophe-

none ketyl; dichloromethane, benzene, diisopropylamine, triethyl-

amine, and trimethylsilyl chloride were distilled from calcium hydride.

Hexane and cyclohexane were used as received. Triethylsilyl chloride,

dimethylphenylsilyl chloride, and diphenylmethylsilyl chloride were

used as received. Methyllithium (1.4 M in diethyl ether), n-butyllithum

(1.6 M in hexanes), and sec-butyllithium (1.4 M in cyclohexane) were

1

Synthesis of Cyclic Ethers 1 and/or 2: General Procedure F. To a

solution of bisallylic ether S3 (0.96 mmol) in dichloromethane

(10 mL) was added second-generation Grubbs catalyst, and the

mixture was stirred at room temperature under nitrogen. After 3 h the

solution was concentrated by rotary evaporation and the residue

puriﬁed by column chromatography.

titrated with diphenylacetic acid (average of three runs). H NMR

spectra were collected on 500 and 600 MHz instruments using CDCl₃

as the solvent, which was referenced at 7.24 ppm (residual chloroform

proton), and ¹³C NMR spectra were collected in CDCl₃at 126 or

151 MHz and referenced at 77 ppm. High-resolution mass spectro-

metry (HRMS) analysis was performed on TOF instruments. Optical

rotations were measured at a wavelength of 589 nm (sodium ^Dline) in

chloroform. Enantiomeric excess was determined by HPLC analysis.

Melting points are not corrected. The crystal structures of 4s and 7

were deposited in the Cambridge Crystallographic Data Centre and

allocated deposition numbers CCDC 1027999 and 1028000.

General Methods. Preparation of Trichloroacetimidates S1:

General Procedure A. To a solution of the corresponding homoallylic

alcohol (∼110 mmol) in diethyl ether (12 mL) was added slowly

sodium hydride (0.15 equiv, dispersion in mineral oil, 60% (w/w)).

The mixture was stirred vigorously for 5 min and then cooled in an ice

bath. Trichloroacetonitrile (1 equiv) was then added dropwise, within

5 min approximately. The ice bath was removed after 15 min and the

mixture stirred for about 1 h at room temperature and then concen-

trated by rotary evaporation. A solution of dry methanol (0.15 equiv)

in pentane (12 mL) was added to precipitate salts. The solids were

ﬁltered through a plug a Celite and rinsed with pentane. The ﬁltrate

was concentrated by rotary evaporation, and the crude product could

be used without further puriﬁcation in the next step. However, in all

cases the crude product was partially puriﬁed by silica gel column

chromatography (typically 5% EtOAc in hexanes) buﬀered with ∼1%

triethylamine.

Synthesis of Cyclic Ethers 1 and/or 2: General Procedure G. A

round-bottom ﬂask was charged with bisallylic ether S3 (0.96 mmol),

which was dissolved in benzene (0.05−0.07 M). Second-generation

Grubbs catalyst was added, and a condenser was attached to the ﬂask.

The system was ﬂushed with nitrogen and then heated in an oil bath at

80 °C for 1 h. The reaction mixture was then cooled at room tem-

perature and concentrated and the product puriﬁed by column

chromatography. Important note: All 2-silyl-6-aryl-5,6-dihydropyrans

1 and 2 are air sensitive and upon isolation undergo autoxidation

1

(observable by H NMR within 1 h after isolation), which is mini-

mized when the compound is diluted (<0.05 M). For this reason,

freshly puriﬁed dihydropyrans 1 and 2 were immediately submitted to

the Wittig rearrangement conditions (general procedure H).

Wittig Rearrangements of 2-Silyl-6-aryl-5,6-dihydropyrans: Gen-

eral Procedure H. Freshly prepared and puriﬁed 2-silyl-6-aryldihy-

dropyran 1 or 2 was dissolved in THF under nitrogen (concentration

0.08 M, unless otherwise noted) and the solution cooled at −78 °C

(dry ice/acetone bath), n-butyllithium (1.2 equiv, 1.6 M in hexanes,

conditions A and C) or sec-butyllithium (3.0 equiv, 1.4 M in cyclo-

hexane, conditions B and D) was added dropwise (1 drop/s) to give a

colored solution. After the indicated time (10−30 min for trans

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The Journal of Organic Chemistry

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diastereomers 1 or 3−7 h for cis diastereomers 2), the reaction was

quenched by adding NH₄Cl(satd) and diluted with H₂O and diethyl

ether. The aqueous phase was extracted with diethyl ether three times.

Combined organic extracts were washed with NH₄Cl(satd), H₂O, and

brine. The solution was dried over magnesium sulfate, ﬁltered, quickly

concentrated in a rotovap at room temperature (no eﬀort was made

to remove all THF to minimize the time the crude reaction was

concentrated), and immediately loaded into a buﬀered column (packed

with ∼1% triethylamine). Elution with 5% and 10% EtOAc in hexanes

aﬀorded the acylsilane and cyclopentenol products, respectively.

Preparation of Starting Materials, Precursors, and Products.

Synthesis of Trichloroacetimidates S1. Preparation of 1-(2-

Methoxyphenyl)but-3-en-1-yl 2,2,2-Trichloroacetimidate (S1-b).

Applying general procedure A to 1-(2-methoxyphenyl)but-3-en-1-ol

(13 g, 73.4 mmol, 1 equiv), sodium hydride (0.44 g, 60% (w/w) oil

dispersion, 0.15 equiv), trichloroacetonitrile (10.6, 73.4 mmol,

1 equiv), and diethyl ether (24 mL) aﬀorded after column chromato-

graphy (5% EtOAc in hexanes, column buﬀered with Et₃N) 18.4 g

(78%) of compound S1-b as a yellow oil: ¹H NMR (500 MHz,

CDCl₃) δ 8.25 (s, 1 H), 7.42 (dd, J = 1.2, 7.8 Hz, 1 H), 7.24 (m, 1 H),

6.94 (t, J = 7.8 Hz, 1 H), 6.87 (d, J = 7.8 Hz, 1 H), 6.28 (t, J = 6.6 Hz,

1 H), 5.84 (m, 1 H), 5.08 (dd, J = 1.8, 16.8 Hz, 1 H), 5.03 (d, J =

10.2 Hz, 1 H); ¹³C NMR (151 MHz, CDCl₃) δ 161.5, 155.9, 133.6,

128.7, 128.4, 125.9, 120.6, 117.6, 110.4, 91.8, 75.0, 55.5, 39.6; IR (ﬁlm)

3344, 3070, 2955, 1664, 1300, 1076, 794 cm⁻¹.

(500 MHz, CDCl₃) δ 8.22 (s, 1 H), 7.44 (m, 1 H), 7.20−7.13 (m,

3 H), 6.04 (dd, J = 5.0, 8.0 Hz, 1 H), 5.82 (ddt, J = 7.0, 10.5, 17.5 Hz,

1 H), 5.12 (dq, J = 1.5, 17.0 Hz, 1 H), 5.07 (m, 1 H), 2.74 (m, 1 H),

2.57 (m, 1 H), 2.42 (s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.4,

138.2, 135.0, 133.3, 130.2, 127.8, 126.2, 125.5, 118.0, 91.7, 77.1, 40.3,

19.2; IR (ﬁlm) 3344, 3078, 2980, 1662, 1311, 1078, 796 cm⁻¹.

Preparation of 1-(4-Methylphenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-g). Applying general procedure A to 1-(4-methyl-

phenyl)but-3-en-1-ol (6.5 g, 40.07 mmol, 1 equiv), sodium hydride

(0.24 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile

(5.79 g, 40.1 mmol, 1 equiv), and diethyl ether (14 mL) aﬀorded after

column chromatography (4% EtOAc in hexanes, column buﬀered with

1

Et₃N) 11.08 g (90%) of compound S1-g as a semisolid: H NMR

(500 MHz, CDCl₃) δ 8.26 (s, 1 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.16 (d,

J = 8.0 Hz, 2 H), 5.84 (dd, J = 5.0, 7.5 Hz, 1 H), 5.80 (ddt, J = 7.0,

10.5, 17.5 Hz, 1 H), 5.11 (dq, J = 1.5, 17.5 Hz, 1 H), 5.07 (m, 1 H),

2.77 (m, 1 H), 2.61 (m, 1 H), 2.33 (s, 3 H); ¹³C NMR (126 MHz,

CDCl₃) δ 161.5, 137.7, 136.6, 133.2, 129.1 (2 C), 126.2 (2 C), 118.1,

91.7, 80.1, 41.0, 21.2; IR (ﬁlm) 3335, 3060, 1662, 1310, 1060 cm⁻¹.

Preparation of 1-(4-Fluorophenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-h). Applying general procedure B to 1-(4-ﬂuorophen-

yl)-3-en-1-ol (4.07 g, 24.49 mmol, 1 equiv), trichloroacetonitrile

(5.3 g, 36.74 mmol, 1 equiv), and DBU (810 mg, 5.31 mmol,

0.18 equiv) in CH₂Cl₂(150 mL) aﬀorded after column chromatog-

raphy (5% EtOAc in hexanes, column buﬀered with Et₃N) 6.25 g

(82%) of compound S1-h as a yellow oil: ¹H NMR (600 MHz,

CDCl₃) δ 8.28 (s, 1 H), 7.36 (m, 2 H), 7.02 (m, 2 H), 5.84 (dd, J =

5.4, 7.8 Hz, 1 H), 5.76 (ddt, J = 7.2, 10.2, 17.4, 1 H), 5.11−5.06 (m,

2 H), 2.76 (m, 1 H), 2.60 (m, 1 H); ¹³C NMR (151 MHz, CDCl₃) δ

162.4 (J = 246.4 Hz), 161.4, 135.3 (d, J = 3.2 Hz), 132.7, 128.1 (d, J =

8.5 Hz, 2 C), 118.4 (d, J = 3.2 Hz), 115.3 (d, J = 21.1 Hz, 2 C), 91.6,

79.4 (d, J = 1.7 Hz), 40.9; IR (ﬁlm) 3343, 3083, 2982, 1664, 1512,

1230, 1076, 796 cm⁻¹.

Preparation of 1-(3-Methoxyphenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-c). Applying general procedure A to 1-(3-

methoxyphenyl)but-3-en-1-ol (13 g, 72.9 mmol, 1 equiv), sodium

hydride (0.29 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloro-

acetonitrile (10.5 g, 72.9 mmol, 1 equiv), and diethyl ether (24 mL)

aﬀorded after column chromatography (5% EtOAc in hexanes, column

buﬀered with Et₃N) 19.88 g (85%) of compound S1-c as a yellow oil:

¹H NMR (500 MHz, CDCl₃) δ 8.30 (s, 1 H), 7.27 (t, J = 8.0 Hz, 1 H),

6.97 (m, 2 H), 6.83 (dd, J = 2.5, 8.0 Hz, 1 H), 5.86 (m, 1 H), 5.81 (m,

1 H), 5.13 (m, 1 H), 5.08 (m, 1 H), 3.79 (s, 3 H), 2.78 (m, 1 H), 2.64

(m, 1 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.4, 159.6, 141.3, 133.0,

129.4, 118.4, 118.1, 113.3, 111.6, 91.7, 79.9, 55.1, 41.0; IR (ﬁlm) 3341,

3070, 2936, 1664, 1290, 1078, 796 cm⁻¹.

Preparation of 1-(4-Chlorophenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-i). Applying general procedure A to 1-(4-chloro-

phenyl)but-3-en-1-ol (11 g, 60.22 mmol, 1 equiv), sodium hydride

(0.36 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile

(8.7 g, 60.22 mmol, 1 equiv), and diethyl ether (21 mL) aﬀorded after

column chromatography (5% EtOAc in hexanes, column buﬀered with

Preparation of 1-(4-Methoxyphenyl)but-3-en-1-yl 2,2,2-Yrichloro-

acetimidate (S1-d). Applying general procedure A to 1-(4-

methoxyphenyl)but-3-en-1-ol (10.7 g, 60 mmol, 1 equiv), sodium hydride

(0.36 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile (8.7 g,

60 mmol, 1 equiv), and diethyl ether (20 mL) aﬀorded after column

chromatography (5% EtOAc in hexanes, column buﬀered with Et₃N)

1

Et₃N) 14.97 g (76%) of compound S1-i as a yellow oil: H NMR

(500 MHz, CDCl₃) δ 8.28 (s, 1 H), 7.32 (s, 4 H), 5.83 (dd, J = 5.5,

7.5 Hz, 1 H), 5.77 (m, 1 H), 5.11−5.06 (m, 2 H), 2.75 (m, 1 H), 2.60

(m, 1 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.4, 138.1, 133.8, 132.6,

128.6 (2 C), 127.7 (2 C), 118.6, 91.5, 79.4, 40.8; IR (ﬁlm) 3343, 3081,

2928, 1664, 1294, 1078, 796 cm⁻¹.

1

12.6 g (65%) of S1-d as a yellow oil: H NMR (500 MHz, CDCl₃) δ

8.26 (s, 1 H), 7.33 (m, 2 H), 6.87 (m, 2 H), 5.83 (m, 1 H), 5.77 (m,

1 H), 5.11 (m, 1 H), 5.06 (m, 1 H), 3.79 (s, 3 H), 2.79 (m, 1 H), 2.61

(m, 1 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.5, 159.3, 133.2, 131.6,

127.7 (2 C), 118.1, 113.7 (2 C), 91.8, 79.9, 55.2, 40.9; IR (ﬁlm) 3340,

3065, 2930, 1664, 1295, 1076, 796 cm⁻¹.

Preparation of 1-(Naphthalen-2-yl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-l). Applying general procedure B to 1-(naphthalen-

2-yl)-3-en-1-ol (4.63 g, 23.3 mmol, 1 equiv), trichloroacetonitrile

(5.05 g, 34.95 mmol, 1 equiv), and DBU (640 mg, 4.19 mmol,

0.18 equiv) in CH₂Cl₂(350 mL) aﬀorded after column chromato-

graphy (8% EtOAc in hexanes, column buﬀered with Et₃N) 7.62 g

(95%) of compound S1-l as a cream-colored solid: mp 42−43 °C; ¹H

NMR (600 MHz, CDCl₃) δ 8.30 (s, 1 H), 7.83 (m, 4 H), 7.53 (dd, J =

1.8, 9.0 Hz, 1 H), 7.47 (m, 2 H), 6.05 (m, 1 H), 5.83 (m, 1 H), 5.13

(m, 1 H), 5.08 (m, 1 H), 2.88 (m, 1 H), 2.71 (m, 1 H); ¹³C NMR

(151 MHz, CDCl₃) δ 161.5, 137.0, 133.1, 133.06, 133.01, 128.3, 128.1,

127.7, 126.2, 126.1, 125.5, 124.0, 118.3, 91.7, 80.3, 40.9; IR (ﬁlm)

3341, 3059, 1664, 1304, 1076, 794 cm⁻¹.

Preparation of 1-(2-Propylphenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-t). Applying general procedure B to 1-(2-propylphen-

yl)-3-en-1-ol (1.5 g, 7.88 mmol, 1 equiv), trichloroacetonitrile (1.7 g,

11.82 mmol, 1 equiv), and DBU (240 mg, 1.58 mmol, 0.2 equiv) in

CH₂Cl₂(40 mL) aﬀorded after column chromatography (5% EtOAc

in hexanes, column buﬀered with Et₃N) 2.15 g (81%) of compound

S1-t as a yellow oil: ¹H NMR (500 MHz, CDCl₃) δ 8.23 (s, 1 H), 7.47

(m, 1 H), 7.21 (m, 2 H), 7.16 (m, 1 H), 6.10 (dd, J = 4.5, 9.0 Hz,

1 H), 5.87 (ddt, J = 7.5, 10.5, 17.5 Hz, 1 H), 5.14 (dq, J = 1.5, 17.0 Hz,

1 H), 5.08 (m, 1 H), 2.75 (m, 2 H), 2.67 (m, 1 H), 2.54 (m, 1 H),

1.77−1.62 (m, 2 H), 1.00 (t, J = 7.5 Hz, 3 H); ¹³C NMR (126 MHz,

CDCl₃) δ 161.4, 139.5, 137.8, 133.6, 129.3, 127.8, 126.1, 125.7, 117.9,

Preparation of 1-(2-Methylphenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-e). Applying general procedure A to 1-(2-methyl-

phenyl)but-3-en-1-ol (4.5 g, 27.74 mmol, 1 equiv), sodium hydride

(0.166 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile

(4 g, 27.74 mmol, 1 equiv), and diethyl ether (10 mL) aﬀorded after

column chromatography (5% EtOAc in hexanes, column buﬀered with

1

Et₃N) 7.29 g (61%) of compound S1-e as a yellow oil: H NMR

(500 MHz, CDCl₃) δ 8.28 (s, 1 H), 7.25 (t, J = 8.0 Hz, 1 H), 7.21 (m,

2 H), 7.12 (d, J = 8.0 Hz, 1 H), 5.86 (dd, J = 5.0, 7.5 Hz, 1 H), 5.83

(m, 1 H), 5.13 (dq, J = 1.5, 17.0 Hz, 1 H), 5.09 (m, 1 H), 2.78 (m,

1 H), 2.62 (m, 1 H), 2.36 (s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ

161.5, 139.6, 137.9, 133.2, 128.7, 128.3, 126.8, 123.1, 118.1, 91.7, 80.2,

41.1, 21.5; IR (ﬁlm) 3418, 1653, 1305, 1085 cm⁻¹.

Preparation of 1-(3-Methylphenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-f). Applying general procedure A to 1-(3-methyl-

phenyl)but-3-en-1-ol (4.22 g, 26 mmol, 1 equiv), sodium hydride

(0.156 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile

(3.75 g, 26 mmol, 1 equiv), and diethyl ether (15 mL) aﬀorded after

column chromatography (5% EtOAc in hexanes, column buﬀered with

1

Et₃N) 6.37 g (80%) of compound S1-f as a yellow oil: H NMR

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91.7, 76.9, 41.1, 34.6, 24.0, 14.2; IR (ﬁlm) 3346, 3078, 2961, 1664,

1309, 1076, 794 cm⁻¹.

further puriﬁcation: ¹H NMR (500 MHz, CDCl₃) δ 6.73 (ddd, J = 5.5,

11.0, 17.0 Hz, 1 H), 5.77 (dt, J = 2.0, 17.0 Hz, 1 H), 5.69 (dt, J = 2.0,

11.0 Hz, 1 H), 4.72 (m, 1 H) 0.76 (s, 9 H); ¹³C NMR (62.8 MHz,

CDCl₃) δ 140.1, 109.6, 69.3, −4.05; IR (neat) 3430, 2959, 1634,

1250 cm⁻¹. S2-a is a known compound and has spectral data in accord

with the reported data.⁷⁸

Preparation of 3-Methyl-1-(4-methylphenyl)but-3-en-1-yl 2,2,2-

Trichloroacetimidate (S1-z). Applying general procedure A to 3-

methyl-1-(p-tolyl)but-3-en-1-ol (4 g, 22.64 mmol, 1 equiv), sodium

hydride (0.136 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloro-

acetonitrile (3.27 g, 42 mmol, 1 equiv), and diethyl ether 8.5 mL)

aﬀorded after column chromatography (5% EtOAc in hexanes, column

buﬀered with Et₃N) 3.1 g (43%) of compound S1-z as a white solid:

mp 59−60 °C; ¹H NMR (500 MHz, CDCl₃) δ 8.23 (s, 1 H), 7.30 (d,

J = 8.0 Hz, 2 H), 7.15 (d, J = 8.0 Hz, 2 H), 5.95 (dd, J = 5.0, 9.0 Hz,

1 H), 4.81 (m, 1 H), 4.76 (m, 1 H), 2.77 (dd, A of ABX system, J =

9.0, 14.5 Hz, 1 H), 2.48 (dd, B of ABX system, J = 5.0, 14.5 Hz, 2 H),

2.33 (s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.6, 140.9, 137.7,

137.1, 129.1 (2 C), 126.2 (2 C), 113.7, 91.7, 79.2, 45.1, 22.8, 21.2; IR

(ﬁlm) 3343, 3070, 2924, 1660, 1304, 1080, 794 cm⁻¹.

Preparation of 1-(Dimethylphenylsilyl)prop-2-en-1-ol (S2-b).^79,80

Applying general procedure C to allyl alcohol (3 g, 51.65 mmol,

1 equiv) in THF (130 mL) at −78 °C, n-BuLi (1.6 M in hexanes,

35 mL, 55.78 mmol, 1.08 equiv), phenyldimethylsilyl chloride (9.52 g,

55.78 mmol, 1.08 equiv), and t-BuLi (1.7 M in pentane, 36.5 mL,

62 mmol, 1.2 equiv) aﬀorded 7.15 g (72%) of S2-b as a colorless oil

1

after column chromatography: H NMR (500 MHz, CDCl₃) δ 7.55

(m, 2 H), 7.36 (m, 3 H), 5.98 (ddd, J = 5.5, 11.0, 17.5 Hz, 1 H), 5.06

(dt, J = 1.5, 17.0 Hz, 1 H), 4.98 (dt, J = 1.5, 11.0 Hz, 1 H), 4.20 (m, 1

H), 0.33 (s, 3 H), 0.32 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ

139.3, 136.0, 134.2 (2 C), 129.5, 127.9 (2 C), 110.1, 68.5, −5.8, −6.1;

IR (ﬁlm) 3426, 3071, 2959, 1427, 1250, 1115, 835 cm⁻¹. S2-b is a

known compound and has spectral data in accord with the reported

data.^79,80

Preparation of 1-(Thiophene-2-yl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-aa). Applying general procedure B to 1-(thiophene-

2-yl)but-3-en-1-ol (2.5 g, 16.21 mmol, 1 equiv), trichloroacetonitrile

(3.51 g, 24.31 mmol, 1 equiv), and DBU (0.44 g, 2.92 mmol, 0.18 equiv)

in CH₂Cl₂(100 mL) aﬀorded after column chromatography (7% EtOAc

in hexanes, column buﬀered with Et₃N) 4.1 g (95%) of compound S1-

Preparation of 1-(Methydiphenylsilyl)prop-2-en-1-ol (S2-c).

Applying general procedure C to allyl alcohol (2 g, 34.48 mmol,

1 equiv) in THF (85 mL), n-BuLi (22 mL, 34.48 mmol, 1.0 equiv),

methyldiphenylsilyl chloride (8.03 g, 34.48 mmol, 1.0 equiv), and

t-BuLi (24 mL, 41.4 mmol, 1.2 equiv) aﬀorded 5.77 g (66%) of S2-c as

colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.62 (m, 4 H), 7.43−7.35

(m, 6 H), 6.04 (ddd, J = 5.5, 11.0, 17.5 Hz, 1 H), 5.12 (dt, J = 2.0, 17.0

Hz, 1 H), 5.02 (dt, J = 2.0, 11.0 Hz, 1 H), 4.59 (m, 1 H), 1.43 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 139.0, 135.1 (2 C), 135.0 (2 C),

134.4, 134.1, 129.7, 129.68, 127.93 (2 C), 129.1 (2 C), 110.8, 67.6,

−7.1; IR (ﬁlm) 3431, 3071, 3041, 3964, 1427, 1115, 904, 790 cm⁻¹.

Preparation of 1-(Triethylsilyl)prop-2-en-1-ol (S2-d).⁸¹Applying

general procedure C to allyl alcohol (2 g, 34.5 mmol, 1 equiv) in THF

(70 mL), n-BuLi (23.7 mL, 37.9 mmol, 1.1 equiv), triethylsilyl chloride

(5.7 g, 37.9 mmol, 1.1 equiv), and s-BuLi (30 mL, 41.4 mmol,

1

aa as a yellow oil: H NMR (500 MHz, CDCl₃) δ 8.37 (s, 1 H), 7.26

(dd, J = 1.5, 5.5 Hz, 1 H), 7.10 (m, 1 H), 6.96 (dd, J = 3.5, 5.0 Hz, 1 H),

6.20 (dd, J = 6.0, 7.5 Hz, 1 H), 5.81 (ddt, J = 6.5, 10.0, 17.0 Hz, 1 H),

5.16 (dq, J = 1.5, 17.5 Hz, 1 H), 5.10 (m, 1 H), 2.88 (m, 1 H), 2.75 (m,

1 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.5, 141.9, 132.6, 126.4, 126.0,

125.4, 118.6, 91.5, 75.6, 40.7; IR (ﬁlm) 3341, 3078, 2943, 1662, 1290,

1072, 794 cm⁻¹.

Preparation of 1-(Furan-2-yl)but-3-en-1-yl 2,2,2-Trichloroaceti-

midate (S1-bb). Applying general procedure B to 1-(furan-2-yl)but-3-

en-1-ol (2.53 g, 18.31 mmol, 1 equiv), trichloroacetonitrile (3.97 g,

27.47 mmol, 1 equiv), and DBU (0.5 g, 3.3 mmol, 0.18 equiv) in

CH₂Cl₂(170 mL) aﬀorded after column chromatography (5% EtOAc

in hexanes, column buﬀered with Et₃N) 2.17 g (42%) of compound

1

S1-bb as a yellow oil: H NMR (500 MHz, CDCl₃) δ 8.37 (s, 1 H),

1.2 equiv) aﬀorded 5.75 g (97%) of S2-d as colorless oil: H NMR

7.39 (dd, J = 1.0, 2.0 Hz, 1 H), 6.39 (d, J = 3.0 Hz, 1 H), 6.33 (dd, J =

2.0, 3.0 Hz, 1 H), 6.00 (t, J = 6.5 Hz, 1 H), 5.77 (ddt, J = 7.0, 10.5,

17.0 Hz, 1 H), 5.15 (dq, J = 1.5, 17.5 Hz, 1 H), 5.08 (m, 1 H), 2.90−

2.78 (m, 2 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.7, 151.5, 142.6,

132.5, 118.4, 110.2, 108.9, 91.5, 73.0, 36.9; IR (ﬁlm) 3343, 3080, 2926,

1662, 1300, 1076, 796 cm⁻¹.

(500 MHz, CDCl₃) δ 6.05 (ddd, J = 5.0, 10.5, 16.0 Hz, 1 H), 5.07 (dd,

J = 1.5, 17.0 Hz, 1 H), 4.96 (dd, J = 1.5, 10.5 Hz, 1 H), 4.16 (m, 1 H),

0.97 (t, J = 8.0 Hz, 9 H), 0.60 (q, J = 8.0 Hz, 6 H); ¹³C NMR

(126 MHz, CDCl₃) δ 140.4, 109.0, 67.4, 7.4, 1.6; IR (ﬁlm) 3402, 2955,

1458, 1097 cm⁻¹. S2-d is a known compound and has spectral data in

accord with the reported data.⁸¹

Preparation of 2-Methyl-1-(trimethylsilyl)prop-2-en-1-ol (S2-e).⁷⁸

Compound S2-e was prepared by a slight modiﬁcation of general

procedure C according to the literature.⁷⁸To a solution of methallyl

alcohol (4 g, 55.5 mmol, 1 equiv) in THF (100 mL) at −78 °C was

added dropwise n-BuLi (38 mL, 61 mmol, 1.1 equiv). After 1 h

trimethylsilyl chloride (7 mL, 55.5 mmol, 1 equiv) was added and the

mixture stirred for an additional 1 h at −78 °C. Then t-BuLi (42 mL,

72 mmol, 1.3 equiv) was added dropwise over a period of 45 min and

the temperature raised to −35 °C for 6 h. The reaction was quenched

by adding a solution of acetic acid (4.1 mL, 72 mmol, 1.3 equiv) in

THF (10 mL) and removal of the cold bath. After 15 min the reaction

was diluted with NaHCO₃(satd) and pentane (300 mL). The organic

phase was washed with H₂O (3 × 50 mL) and brine (50 mL) and

dried over Na₂SO₄. After ﬁltration the residue was carefully concen-

Preparation of 1-(4-Bromophenyl)but-3-en-1-yl 2,2,2-Trichloro-

acetimidate (S1-cc). Applying general procedure A to 1-(4-bromo-

phenyl)but-3-en-1-ol (9.54 g, 42 mmol, 1 equiv), sodium hydride

(0.25 g, 60% (w/w) oil dispersion, 0.15 equiv), trichloroacetonitrile

(6.06 g, 42 mmol, 1 equiv), and diethyl ether (14 mL) aﬀorded after

column chromatography (5% EtOAc in hexanes, column buﬀered with

1

Et₃N) 13.4 g (86%) of S1-cc as a yellow solid: mp 37−38 °C; H

NMR (500 MHz, CDCl₃) δ 8.31 (s, 1 H), 7.48 (m, 2 H), 7.27 (m,

2 H), 5.83 (dd, J = 5.5, 7.5 Hz, 1 H), 5.77 (ddt, J = 6.5, 10.0, 17.0 Hz,

1 H), 5.13−5.07 (m, 2 H), 2.76 (m, 1 H), 2.61 (m, 1 H); ¹³C NMR

(126 MHz, CDCl₃) δ 161.3, 138.6, 132.5, 131.5 (2 C), 128.0 (2 C),

121.9, 118.6, 91.5, 79.3, 40.7; IR (ﬁlm) 3343, 3081, 2934, 1664, 1294,

1072, 794 cm⁻¹.

Synthesis of α-Silyl Allylic Alcohols S2. Preparation of 1-

(Trimethylsilyl)prop-2-en-1-ol (S2-a).⁷⁸A solution of allyl alcohol

(2.73 g, 47.06 mmol) in THF (117 mL) was cooled to −78 °C. n-BuLi

(1.61 M in hexanes, 31.57 mL, 50.83 mmol) was added dropwise and

the mixture stirred for 1 h. Then freshly distilled (TMS)Cl (5.97 mL,

47.06 mmol) was added slowly from a syringe. After 1.5 h t-BuLi

(1.66 M in pentane, 34.02 mL, 63.98 mmol) was added dropwise and

the reaction stirred for an additional 1.5 h. The reaction was quenched

by the addition of aqueous NH₄Cl and diluted with Et₂O, and the mix-

ture was warmed to room temperature. After the layers were separated,

the aqueous phase was washed with Et₂O (3 × 50 mL). Then all the

organic phases were combined, washed with H₂O (4 × 25 mL) and

brine (3 × 17 mL), and dried over Na₂SO₄overnight. Filtration and

concentration furnished the crude product S2-a (65%) as a yellow

THF solution (90.1% pure), which was used in the next step without

1

trated to give 79% S2-e as a THF solution (ca. 76%, w/w): H NMR

(600 MHz, CDCl₃) δ 4.77 (m, 1 H), 4.74 (m, 1 H), 3.85 (s, 1 H), 1.68

(m, 3 H), 1.37 (s, 1 H), 0.05 (s, 9 H).

Preparation of Trimethyl((1-(trimethylsilyl)allyl)oxy)silane (S2-f).

Compound S2-f was prepared by a slight modiﬁcation of general pro-

cedure C prior to workup. Following application of general procedure

C to allyl alcohol (1 g, 17.24 mmol, 1 equiv) in THF (45 mL) at

−78 °C, n-BuLi (1.6 M in hexanes, 11.6 mL, 18.62 mmol, 1.08 equiv),

trimethylsilyl chloride (2.2 mL, 17.24 mmol, 1 equiv), and t-BuLi

(1.7 M in pentane, 12.2 mL, 20.69 mmol, 1.2 equiv) (added dropwise

over ∼50 min and stirred at −78 °C for 2.5 h), the reaction was slowly

treated (5 min) with trimethylsilyl chloride (5.47 mL, 43.1 mmol,

2.5 equiv) and the mixture stirred at −78 °C for 1 h and at room

temperature for 1 h. The reaction was cooled at −78 °C and quenched

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with NaHCO₃(satd) (50 mL) and the mixture diluted immediately

with Et₂O (100 mL). The aqueous phase was extracted with Et₂O (3 ×

50 mL). Combined organic extracts were washed with brine and dried

over MgSO₄. Filtration and evaporation of solvent gave the crude

product (80%), which was almost pure and was used in the next step

without further puriﬁcation. Analytically pure (colorless oil) S2-f was

75.7, 72.9, 55.14, 55.12, 43.0, 41.6, −3.7, −3.9; IR (ﬁlm) 3076, 2957,

1248, 1047, 841 cm⁻¹; HRMS (EI) m/z 290.1685 [(M⁺), calcd for

C₁₇H₂₆O₂Si, 290.1702].

syn/anti-(1-((1-(4-Methoxyphenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-d). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (2 g, 15.35 mmol), trichloroacetimidate S1-d

(9.9 g, 30.7 mmol, 2 equiv), and (TMS)OTf (194 μL, 1.07 mmol,

0.07 equiv) in cyclohexane (85 mL) aﬀorded after column chromato-

graphy (15% CH₂Cl₂in hexanes) 4.35 g (60%) of syn/anti-S3-d

1

obtained by column chromatography on buﬀered silica gel: H NMR

(300 MHz, CDCl₃) δ (5.87 (ddd, J = 5.0, 10.5, 17.0 Hz, 1 H), 5.01

(dd, J = 2.0, 17.0 Hz, 1 H), 4.88 (dd, J = 2.0, 10.5 Hz, 1 H), 3.93 (dd

J³= 2.0, 5.0 Hz, 1 H), 0.067 (s, 9 H), −0.027 (s, 9 H); ¹³C NMR

(62.8 MHz, CDCl₃) δ 139.4, 109.5, 69.2, 0.08, −4.1; IR (neat) 2959,

2901, 2818, 1250, 1020, 841 cm⁻¹.

1

(1:1) as a colorless oil. Spectroscopic data for syn-S3-d: H NMR

(500 MHz, CDCl₃) δ 7.20 (d, J = 8.5 Hz, 2 H), 6.82 (d, J = 8.5 Hz,

2 H), 5.74−5.62 (m, 2 H), 4.96 (m, 2 H), 4.92 (dt, J = 2.0, 17.0 Hz,

1 H), 4.82 (dt, J = 1.5, 10.0 Hz, 1 H), 4.30 (t, J = 6.0 Hz, 1 H), 3.78 (s,

3 H), 3.76 (dt, J = 1.5, 7.0 Hz, 1 H), 2.49 (m, 1 H), 2.39 (m, 1 H),

0.04 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 158.5, 138.0, 135.7,

135.0, 127.7 (2 C), 116.7, 113 (2 C), 111.6, 80.7, 75.5, 55.2, 41.5,

−3.7; IR (ﬁlm) 3076, 2957, 1514, 1248, 1039, 841 cm⁻¹; HRMS (EI)

m/z 290.1688 [(M⁺), calcd for C₁₇H₂₆O₂Si, 290.1702]. Spectroscopic

data for anti-S3-d: ¹H NMR (500 MHz, CDCl₃) δ 7.14 (d, J = 8.5 Hz,

2 H), 6.84 (d, J = 8.0 Hz, 2 H), 5.82−5.68 (m, 2 H), 4.97 (m, 4 H),

4.36 (t, J = 7.0 Hz, 1 H), 3.79 (s, 3 H), 3.39 (dt, J = 1.0, 7.0 Hz, 1 H),

2.51 (m, 1 H), 2.31 (m, 1 H), −0.04 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 158.9, 137.7, 135.6, 134.5, 128.5, 116.2, 113.5, 112.7,

78.7, 72.5, 55.2, 43.0, −4.0; IR (ﬁlm) 3076, 2957, 1514, 1258, 1039,

841 cm⁻¹; HRMS (EI) m/z 290.1695 [(M⁺), calcd for C₁₇H₂₆O₂Si,

290.1702].

Preparation of Trimethyl((1-(trimethylsilyl)but-2-yn-1-yl)oxy)-

silane (S2-g). Compound S2-g was prepared by a slight modiﬁcation

of general procedure C prior to workup. Following general procedure

C, to 2-butyn-1-ol (3 g, 42.8 mmol, 1 equiv) in THF (150 mL) at −78 °C

was slowly added n-BuLi (1.6 M in hexanes, 31 mL, 46.2 mmol,

1.08 equiv). After 30 min trimethylsilyl chloride (5 g, 46.2 mmol,

1.08 equiv) was added and the mixture stirred at the same temperature

for 1 h. Then t-BuLi (1.7 M in pentane, 31 mL, 51.3 mmol, 1.2 equiv)

was added dropwise over ∼1 h, and the yellow mixture was stirred at

−78 °C for 3 h. Trimethylsilyl chloride (6.93 g, 64.2 mmol, 1.5 equiv)

was added slowly (5 min) and the mixture stirred at −78 °C for 1 h

and at room temperature for 1 h. The reaction was cooled at −78 °C

and quenched with NaHCO₃(satd) (50 mL) and the mixture imme-

diately diluted with Et₂O (100 mL). The aqueous phase was extracted

with Et₂O (3 × 50 mL). Combined organic extracts were washed with

brine and dried over MgSO₄. Column chromatography (2% EtOAc

syn/anti-(1-((1-(2-Methylphenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-e). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (1.17 g, 85.5% (w/w) in Et₂O, 8.98 mmol), trichlo-

roacetimidate S1-e (3.85 g, 12.57 mmol, 1.4 equiv), and (TMS)OTf

(40 μL, 0.225 mmol, 0.025 equiv) in cyclohexane (45 mL) aﬀorded

after column chromatography (hexanes) 1.81 g (73%) of syn/anti-S3-e

(1:1) as a colorless oil: mixture of diastereomers (syn:anti S3-e =

1

in hexanes) aﬀorded 6.4 g (70%) of S2-g as a colorless oil: H NMR

(500 MHz, CDCl₃) δ 3.94 (q, J = 2.5 Hz, 1 H), 1.83 (d, J = 2.5 Hz,

3 H), 0.11 (s, 9 H), 0.05 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

82.4, 79.4, 56.5, 3.9, 0.0, −4.2.

Synthesis of α-Silyl Allylic Ethers S3. syn/anti-(1-((1-(2-

Methoxyphenyl)but-3-en-1-yl)oxy)allyl)trimethylsilane (S3-b).

Applying general procedure D to α-(trimethylsilyl)allyl alcohol (2.78 g,

54.7% (w/w) in THF, 1 mmol), trichloroacetimidate S1-b (6.7 g,

20.73 mmol, 1.8 equiv), and (TMS)OTf (trace) in cyclohexane

(64 mL) aﬀorded after column chromatography (10% CH₂Cl₂in

hexanes) 2.58 g (77%) of syn/anti-S3-b (1:1) as a colorless oil: mixture

of diastereomers (syn:anti-S3-b = 1:1); ¹H NMR (500 MHz, CDCl₃) δ

7.45 (dd, J = 1.5, 8.0 Hz, 1 H), 7.34 (dd, J = 1.5, 7.5 Hz, 1 H), 7.18 (m,

2 H), 6.94 (t, J = 7.5 Hz, 1 H), 6.92 (t, J = 7.5 Hz, 1 H), 6.82 (dd, J =

1.0, 8.5 Hz, 1 H), 6.79 (dd, J = 1.0, 8.0 Hz, 1 H), 5.87 (ddt, J = 7.0,

10.5, 17.5 Hz, 1 H), 5.77 (m, 2 H), 5.65 (ddd, J = 7.0, 10.5, 17.5 Hz,

1 H), 5.01−4.87 (m, 8 H), 4.80 (m, 2 H), 3.79 (dt, J = 1.5, 7.5 Hz,

1 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 3.44 (dt, J = 1.0, 7.5 Hz, 1 H), 2.47−

2.35 (m, 4 H), 0.04 (s, 9 H), −0.01 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 157.4, 155.7, 138.02, 137.98, 135.9, 135.4, 132.3, 131.0,

127.8, 127.5, 127.4, 127.3, 120.4, 120.2, 116.2, 115.9, 112.7, 111.7,

110.3, 109.9, 75.6, 74.4, 73.2, 72.5, 55.4, 55.3, 41.9, 39.9, −3.7, −3.9;

IR (ﬁlm) 3076, 2957, 2835, 1489, 1244, 841 cm⁻¹; HRMS (EI) m/z

290.1700 [(M⁺), calcd for C₁₇H₂₆O₂Si, 290.1702].

1

1.0:0.5); H NMR (500 MHz, CDCl₃) δ 7.45 (dd, J = 1.0, 7.5 Hz,

1 H), 7.38 (dd, J = 1.5, 7.5 Hz, 0.5 H), 7.23 (m, 4.5 H), 5.86 (ddt, J =

7.0, 10.0, 17.0 Hz, 0.5 H), 5.79 (m, 1.5 H), 5.63 (ddd, J = 7.5, 10.5,

18.0 Hz, 1 H), 5.06−4.96 (m, 4 H), 4.91 (ddd, J = 1.5, 2.0, 17.5 Hz,

1 H), 4.81 (ddd, J = 1.5, 2.0, 10.0 Hz, 1 H), 4.77 (dd, J = 5.0, 8.0 Hz,

0.5 H), 4.56 (dd, J = 5.5, 6.5 Hz, 1 H), 3.79 (dt, J = 1.0, 7.5 Hz, 1 H),

3.39 (dt, J = 1.5, 8.0 Hz, 0.5 H), 2.52−2.44 (m, 1.5 H), 2.41−2.29 (m,

1.5 H), 2.28 (s, 4.5 H), 0.07 (s, 9 H), 0.01 (s, 4.5 H); ¹³C NMR

(151 MHz, CDCl₃) (syn-S3-e, major) δ 142.1, 138.06, 135.1, 134.0,

129.8, 126.7, 126.57, 125.7, 116.7, 111.8, 78.2, 75.0, 41.1, 19.3, −3.7;

(anti S3-e, minor) δ 140.7, 138.1, 135.9, 135.6, 129.9, 126.8, 126.60,

125.9, 116.3, 113.1, 76.6, 73.0, 42.3, 19.1, −3.9; IR (ﬁlm) 3077, 2957,

1247, 1060, 842 cm⁻¹; HRMS (EI) m/z 274.1753 [(M⁺), calcd for

C₁₇H₂₆OSi, 274.1753].

syn/anti-(1-((1-(3-Methylphenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-f). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (1.17 g, 85.5% (w/w) in Et₂O, 8.98 mmol), trichlo-

roacetimidate S1-f (3.85 g, 12.57 mmol, 1.4 equiv), and (TMS)OTf

(162 μL, 0.898 mmol, 0.1 equiv) in cyclohexane (45 mL) aﬀorded

after column chromatography (hexanes) 1.38 g (56%) of syn/anti-S3-f

(1:1) as a colorless oil. Spectroscopic data for syn-S3-f: ¹H NMR

(500 MHz, CDCl₃) δ 7.17 (t, J = 8.0 Hz, 1 H), 7.08 (m, 2 H), 7.02 (d,

J = 7.5 Hz, 1 H), 5.72 (ddt, J = 7.0, 10.0, 17.5 Hz, 1 H), 5.67 (ddd, J =

7.0, 10.5, 17.5 Hz, 1 H), 5.01−4.93 (m, 2 H), 4.91 (dt, J = 2.0, 17 Hz,

1 H), 4.83 (ddd, J = 1.5, 2.0, 10.5 Hz, 1 H), 4.33 (t, J = 6.0 Hz, 1 H),

3.79 (dt, J = 1.5, 7.0 Hz, 1 H), 2.50 (m, 1 H), 2.40 (m, 1 H), 2.33 (s,

3 H), 0.05 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.5, 137.9,

137.3, 135.0, 127.7, 127.6, 127.3, 123.7, 116.7, 111.8, 104.7, 81.0, 75.6,

41.6, 21.5, −3.7; IR (ﬁlm) 3079, 2958, 1247, 910, 845 cm⁻¹; HRMS

(EI) m/z 274.1750 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753]. Spectro-

syn/anti-(1-((1-(3-Methoxyphenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-c). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (1.83 g, 54.7% (w/w) in THF, 7.68 mmol), trichlo-

roacetimidate S1-c (4.46 g, 13.8 mmol, 1.8 equiv), and (TMS)OTf

(97 μL, 0.538 mmol, 0.07 equiv) in cyclohexane (43 mL) aﬀorded

after column chromatography (15% CH₂Cl₂in hexanes) 1.34 g (60%)

of syn/anti-S3-c (1:1) as a colorless oil: mixture of diastereomers

1

(syn:anti-S3-c = 1:0.4); H NMR (500 MHz, CDCl₃) δ 7.21 (t, J =

8.0 Hz, 0.4 H), 7.19 (t, J = 8.0 Hz, 1 H), 6.88 (m, 1 H), 6.85 (m, 1 H),

6.80 (m, 1.2 H), 6.75 (ddd, J = 1.0, 2.5, 8.0 Hz, 1 H), 5.80 (m, 0.4 H),

5.71 (m, 1.4 H), 5.67 (ddd, J = 2.0, 10.5, 17.0 Hz, 1 H), 5.03−4.95 (m,

3.6 H), 4.92 (dt, J = 1.5, 17.0 Hz, 1 H), 4.83 (dt, J = 1.5, 11.0 Hz,

1 H), 4.40 (dd, J = 6.0, 8.0 Hz, 0.4 H), 4.34 (t, J = 6.0 Hz, 1 H), 3.79

(s, 1.2 H), 3.78 (s, 3 H), 3.77 (dt, J = 1.5, 7.0 Hz, 1 H), 3.44 (dt, J =

1.5, 7.5 Hz, 0.4 H), 2.48 (m, 1.4 H), 2.41 (m, 1 H), 2.32 (m, 0.4 H),

0.04 (s, 9 H), −0.02 (s, 3.6 H); ¹³C NMR (126 MHz, CDCl₃) δ 159.6,

159.3, 145.3, 144.3, 137.8, 137.5, 135.4, 134.8, 129.0, 128.8, 119.8,

119.0, 116.8, 116.4, 113.0, 112.9, 112.3 (2 C), 112.1, 111.9, 80.8, 79.1,

1

scopic data for anti-S3-f: H NMR (500 MHz, CDCl₃) δ 7.19 (t, J =

7.5 Hz, 1 H), 7.06 (m, 2 H), 7.02 (d, J = 8.0 Hz, 1 H), 5.81 (ddt J =

7.0, 10.0, 17.0 Hz, 1 H), 5.73 (ddd, J = 7, 10.5, 17.0 Hz, 1 H), 5.01 (m,

1 H), 4.97 (m, 1 H), 4.39 (dd, J = 5.5, 8.0 Hz, 1 H), 3.42 (dt, J = 1.0,

7.9 Hz, 1 H), 2.51 (m, 1H), 2.34 (s, 3 H), 2.31 (m 1 H), −0.02 (s,

9 H); ¹³C NMR (151 MHz, CDCl₃) δ 142.5, 137.63, 137.62, 135.6,

128.0, 127.96, 127.95, 124.4, 116.2, 112.7, 79.2, 72.8, 43.1, 21.4, −3.9;

L

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

IR (ﬁlm) 3079, 2959, 1247, 911, 842 cm⁻¹; HRMS (EI) m/z 274.1741

[(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

(862 mg, 4.95 mmol, 1 equiv), allyltrimethylsilane (625 mg, 4.95 mmol,

1 equiv), and (TMS)OTf (180 μL, 0.989 mmol, 0.2 equiv) in CH₂Cl₂

(50 mL) for 30 min at −78 °C aﬀorded after workup and column chro-

matography (10% CH₂Cl₂in hexanes) 765 mg of a mixture of anti/syn-

S3-j (4:1) as a colorless oil: mixture of diastereomers (anti:syn-S3-j =

syn/anti-(1-((1-(4-Methylphenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-g). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (2.78 g, 54% (w/w) in Et₂O, 11.52 mmol, 1 equiv),

trichloroacetimidate S1-g (6 g, 19.58 mmol, 1.7 equiv), and (TMS)OTf

(trace, <0.02 equiv) in hexane (64 mL) aﬀorded after column

chromatography (hexanes) 2.38 g (75%) of syn/anti-S3-g (1:1) as a

1

0.8:0.2); H NMR (600 MHz, CDCl₃) δ 7.59 (d, J = 7.8 Hz, 1.6 H),

7.56 (d, J = 7.8 Hz, 0.4 H), 7.42 (d, J = 8.4 Hz, 0.4 H), 7.37 (d, J =

7.8 Hz, 1.6 H), 5.83−5.73 (m, 1.6 H), 5.71−5.64 (m, 0.4 H), 5.07 (m,

0.8 H), 5.03−4.98 (m, 2.8 H), 4.92 (dt, J = 1.8, 17.4 Hz, 0.2 H), 4.86

(dt, J = 1.8, 10.8 Hz, 0.2 H), 4.53 (dd, J = 6.6, 7.8 Hz, 0.8 H), 4.47 (t,

J = 6.0 Hz, 0.2 H), 3.84 (dt, J = 1.8, 7.2 Hz, 0.2 H), 3.40 (d, J = 7.8 Hz,

0.8 H), 2.53 (m, 1 H), 2.46 (m, 0.2 H), 2.36 (m, 0.8 H), 0.09 (s, 1.8 H),

0.02 (s, 7.2 H); ¹³C NMR (151 MHz, CDCl₃) (anti) δ 146.7, 137.2,

134.6, 129.6 (q, J = 32.3 Hz), 127.6 (2 C), 125.1 (q, J = 3.78 Hz, 2 C),

124.3 (q, J = 272.0 Hz), 117.0, 113.4, 78.7, 73.5, 42.9, −4.0; (syn) δ

147.7, 137.5, 134.0, 129.1 (q, J = 32.1 Hz), 126.8 (2 C), 124.9 (q, J =

3.6 Hz, 2 C), CF₃carbon could not be located, 117.5, 112.4, 80.3, 76.2,

41.3, −3.8; IR (ﬁlm) 3080, 2959, 1325, 1128, 841 cm⁻¹; HRMS (EI)

m/z 328.1457 [(M⁺), calcd for C₁₇H₂₃OSiF₃, 328.1470].

syn/anti-(1-((1-([1,1′-Biphenyl]-4-yl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-k). To a solution of syn/anti-S3-z (1:1, 342 mg,

1.01 mmol, 1 equiv) in THF (2.2 mL) was added S-Phos (4.2 mg,

0.02 mmol, 0.02 equiv), phenylboronic acid (184 mg, 1.512 mmol,

1.5 equiv), and K₃PO₄·2H₂O (500 mg, 2.016 mmol, 2 equiv). The

mixture was degassed with three freeze−pump−thaw cycles, and then

Pd(OAc)₂(2.3 mg, 0.01 mmol, 0.01 equiv) was added at room tem-

perature. The mixture was stirred at room temperature under a

nitrogen atmosphere and the reaction monitored by TLC (hexanes).

After 9 h the reaction was concentrated and the residue subjected to

column chromatography (10% CH₂Cl₂in hexanes) to aﬀord a total of

327 mg (53%) of syn/anti-S3-k (1:1). Diastereomers were partially

separated. Spectroscopic data for syn-S3-k: ¹H NMR (600 MHz,

CDCl₃) δ 7.60 (m, 2 H), 7.54 (d, J = 8.4 Hz, 2 H), 7.43 (t, J = 7.2 Hz,

2 H), 7.37 (d, J = 8.4 Hz, 2 H), 7.33 (tt, J = 1.2, 7.2 Hz, 1 H), 5.77

(ddt, J = 7.2, 10.2, 17.4 Hz, 1 H), 5.72 (ddd, J = 7.2. 10.8, 18.0 Hz,

1 H), 5.04−4.98 (m, 2 H), 4.96 (dt, J = 1.8, 16.8 Hz, 1 H), 4.87 (dt,

J = 1.8, 10.8 Hz, 1 H), 4.45 (t, J = 6.0 Hz, 1 H), 3.85 (dt, J = 1.2,

7.2 Hz, 1 H), 2.57 (m, 1 H), 2.49 (m, 1 H), 0.09 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 142.7, 141.1, 139.7, 137.9, 134.8, 128.7 (2 C),

127.04, 127.02 (2 C), 126.97 (2 C), 126.6 (2 C), 116.9, 112.0, 80.6,

75.7, 41.4, −3.7; IR (ﬁlm) 3077, 2957, 1250, 840 cm⁻¹; HRMS (EI)

m/z 336.1923 [(M⁺), calcd for C₂₂H₂₈OSi, 336.1909]. Spectroscopic

data for anti-S3-k: ¹H NMR (600 MHz, CDCl₃) δ 7.61 (d, J = 7.8 Hz,

2 H), 7.56 (d, J = 7.8 Hz, 2 H), 7.44 (t, J = 7.8 Hz, 2 H), 7.33 (m,

3 H), 5.85 (ddt, J = 7.2, 10.2, 17.4 Hz, 1 H), 5.77 (ddd, J = 7.8, 10.8,

18.0 Hz, 1 H), 5.07−5.00 (m, 4 H), 4.50 (dd, J = 5.4, 7.8 Hz, 1 H),

3.49 (d, J = 7.2 Hz, 1 H), 2.58 (m, 1 H), 2.40 (m, 1 H), 0.01 (s, 9 H);

¹³C NMR (151 MHz, CDCl₃) δ 141.6, 140.9, 140.2, 137.6, 135.4,

1

colorless oil. Spectroscopic data for syn S3-g: H NMR (500 MHz,

CDCl₃) δ 7.17 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 8.5 Hz, 2 H), 5.72 (m,

1 H), 5.67 (m, 1 H), 5.01−4.90 (m, 3 H), 4.83 (m, 1 H), 4.34 (t, J =

6.0 Hz, 1 H), 3.78 (dt, J = 1.5, 7.0 Hz, 1 H), 2.51 (m, 1 H), 2.41 (m,

1 H), 2.32 (s, 3 H), 0.05 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

140.5, 137.9, 136.4, 135.0, 128.6 (2C), 126.5 (2C), 116.7, 111.7, 80.8,

75.5, 41.5, 21.1, −3.7; IR (ﬁlm) 3070, 2959, 1514, 1248, 1062, 910,

841 cm⁻¹; HRMS (EI) m/z 274.1749 [(M⁺), calcd for C₁₇H₂₆OSi,

274.1753]. Spectroscopic data for anti-S3-g: ¹H NMR (500 MHz,

CDCl₃) δ 7.13 (s, 4 H), 5.81 (m, 1 H), 5.74 (m, 1 H), 5.04−4.95 (m,

4 H), 4.40 (dd, J = 6.0, 7.5 Hz, 1 H), 3.43 (dt, J = 1.0, 7.5 Hz, 1 H),

2.53 (m, 1 H), 2.34 (s, 3 H), 2.33 (m, 1 H), −0.01 (s, 9 H); ¹³C NMR

(126 MHz, CDCl₃) δ 139.4, 137.7, 136.9, 135.6, 128.8 (2 C), 127.3

(2 C), 116.2, 112.8, 79.0, 72.7, 43.1, 21.2, −4.0; IR (ﬁlm) 3076, 2957,

1514, 1248, 1057, 910, 841 cm⁻¹; HRMS (EI) m/z 274.1753 [(M⁺),

calcd for C₁₇H₂₆OSi, 274.1753].

syn/anti-(1-((1-(4-Fluorophenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-h). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (1.26 g, 69.9% (w/w) in THF, 6.73 mmol,

1 equiv), trichloroacetimidate S1-h (2.9 g, 9.43 mmol, 1.4 equiv), and

(TMS)OTf (121 μL, 0.673 mmol, 0.1 equiv) in hexane (37 mL)

aﬀorded after column chromatography (hexanes) a total of 724 mg

(39%) of syn/anti-S3-h (1:1) as a colorless oil. Diastereomers were

partially separated. Spectroscopic data for syn-S3-h: ¹H NMR

(500 MHz, CDCl₃) δ 7.23 (dd, J = 6.0, 9.0 Hz, 2 H), 6.96 (t, J =

9.0 Hz, 2 H), 5.65 (m, 2 H), 4.96 (m, 2 H), 4.87 (dt, J = 1.5, 17.0 Hz,

1 H), 4.83 (dt, J = 1.5, 10.5 Hz, 1 H), 4.33 (t, J = 6.0 Hz, 1 H), 3.77

(dt, J = 1.5, 7.0 Hz, 1 H), 2.48 (m, 1 H), 2.38 (m, 1 H), 0.03 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 161.8 (d, J = 245.1 Hz), 139.2 (d, J =

3.2 Hz), 137.7, 134.5, 128.1 (d, J = 7.9 Hz, 2 C), 117.1, 114.6 (d, J =

21.7 Hz, 2 C), 111.9, 80.4, 75.8, 41.4, −3.8; IR (ﬁlm) 3078, 2959,

1518, 1224, 839 cm⁻¹; HRMS (EI) m/z 278.1505 [(M⁺), calcd for

1

C₁₆H₂₃OSiF, 278.1502]. Spectroscopic data for anti-S3-h: H NMR

(500 MHz, CDCl₃) δ 7.18 (dd, J = 5.5, 8.0 Hz, 2 H), 6.99 (t, J =

8.5 Hz, 2 H), 5.73 (m, 2 H), 5.02−4.94 (m, 4 H), 4.39 (t, J = 6.5 Hz,

1 H), 3.36 (d, J = 7.5 Hz, 1 H), 2.50 (m, 1 H), 2.31 (m, 1 H), −0.04

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 162.2 (d, J = 245.3 Hz),

138.1 (d, J = 3.2 Hz), 137.4, 135.1, 128.8 (d, J = 7.9 Hz, 2 C), 116.6,

114.9 (d, J = 21.3 Hz, 2 C), 113.0, 78.6, 73.0, 43.0, −4.0; IR (ﬁlm)

3078, 2959, 1518, 1224, 835 cm⁻¹; HRMS (EI) m/z 278.1492 [(M⁺),

calcd for C₁₆H₂₃OSiF, 278.1502].

128.7 (2 C), 127.7 (2 C), 127.2, 127.0 (2 C), 126.8 (2 C), 116.5,

112.9, 78.9, 72.9, 43.1, −3.9; IR (ﬁlm) 3077, 2957, 1247, 840 cm⁻¹;

HRMS (EI) m/z 336.1920 [(M⁺), calcd for C₂₂H₂₈OSi, 336.1909].

syn/anti-(1-((1-(Naphthalen-2-yl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-l). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (1.07 g, 44% (w/w) in THF, 5.72 mmol, 1 equiv),

trichloroacetimidate S1-l (2.74 g, 8 mmol, 1.4 equiv), and (TMS)OTf

(47 μL, 0.259 mmol, 0.05 equiv) in hexane (32 mL) aﬀorded after

column chromatography (10% CH₂Cl₂in hexanes) a total of 852 mg

(48%) of syn/anti-S3-l (1:1) as a colorless oil. Compounds syn- and

anti-S3-l were separable by column chromatography. Spectroscopic

data for syn-S3-l: ¹H NMR (500 MHz, CDCl₃) δ 7.81 (m, 2 H), 7.78

(dd, J = 1.5, 8.5 Hz, 1 H), 7.72 (s, 1 H), 7.45 (m, 3 H), 5.80−5.63 (m,

2 H), 5.02−4.96 (m, 2 H), 4.92 (dq, J = 2.0, 15.0 Hz, 1 H), 4.81 (dq,

J = 1.5, 10.5 Hz, 1 H), 4.53 (m, 1 H), 3.59 (dq, J = 1.5, 7.0 Hz, 1 H),

2.61 (m, 1 H), 2.51 (m, 1 H), 0.08 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 141.1, 137.9, 134.8, 133.1, 132.8, 127.9, 127.6, 127.5, 125.8,

125.4, 125.3, 125.0, 116.9, 111.9, 81.3, 75.9, 41.5, −3.7; IR (ﬁlm) 3060,

2959, 2825, 1241, 860, 841 cm⁻¹; HRMS (EI) m/z 310.1753 [(M⁺),

calcd for C₂₀H₂₆OSi, 310.1753]. Spectroscopic data for anti-S3-l:

¹H NMR (500 MHz, CDCl₃) δ 7.81 (m, 3 H), 7.65 (s, 1 H), 7.44

(m, 3 H), 5.86−5.72 (m, 2 H), 5.06−4.96 (m, 4 H), 4.59 (dd, J = 6.0,

syn/anti-(1-((1-(4-Chlorophenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-i). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (5.5 g, solution 36.2% (w/w) in THF, 15.35 mmol,

1 equiv), trichloroacetimidate S1-i (10 g, 30.7 mmol, 2 equiv), and

(TMS)OTf (190 μL, 1.07 mmol, 0.07 equiv) in cyclohexane (85 mL)

aﬀorded after column chromatography (hexanes) 1.425 g (54%) of

syn/anti-S3-i (1:1) as a colorless oil: mixture of diastereomers (syn:anti

S3-i = 0.7:1.0); ¹H NMR (500 MHz, CDCl₃) δ 7.27 (m, 3.4 H), 7.24

(m, 2 H), 7.18 (m, 1.4 H), 5.82−5.62 (m, 3.4 H), 5.04 (m, 0.7 H),

5.02−4.96 (m, 4.1 H), 4.90 (dt, J = 1.5, 17.0 Hz, 1 H), 4.85 (dt, J =

1.5, 11.0 Hz, 1 H), 4.42 (dd, J = 6.0, 7.0 Hz, 0.7 H), 4.36 (t, J = 6.0 Hz,

1 H), 3.80 (dt, J = 1.5, 7.0 Hz, 1 H), 3.39 (m, 0.7 H), 2.55−2.30 (m,

3.4 H), 0.06 (s, 9 H), −0.01 (s, 7.3 H); ¹³C NMR (126 MHz, CDCl₃)

δ 142.1, 140.9, 137.7, 137.3, 134.9, 134.7, 134.3, 133.0, 132.5, 128.7 (2

C), 128.3 (2 C), 128.2, 128.0 (2 C), 127.9 (2 C), 127.4, 117.2, 116.8,

113.1, 112.1, 80.3, 78.6, 75.9, 73.1, 42.9, 41.3, −3.8, −4.0; IR (ﬁlm)

3078, 2957, 1491, 1248, 1089, 841 cm⁻¹; HRMS (EI) m/z 294.1218

[(M⁺), calcd for C₁₆H₂₃OSiCl, 294.1207].

syn/anti-(1-((1-(4-(Triﬂuoromethyl)phenyl)but-3-en-1-yl)oxy)-

allyl)trimethylsilane (S3-j). Applying general procedure E to alcohol

S2-f (1 g, 4.95 mmol, 1 equiv), 4-(triﬂuoromethyl)benzaldehyde

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7.5 Hz, 1 H), 3.44 (m, 1 H), 2.62 (m, 1 H), 2.43 (m, 1 H), −0.02 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 139.8, 137.5, 135.3, 133.1, 133.0,

128.0, 127.8, 127.7, 126.5, 125.9, 125.6, 125.1, 116.5, 112.9, 79.3, 72.9,

42.8, −4.0; IR (ﬁlm) 3057, 2959, 2831, 1246, 859, 841 cm⁻¹; HRMS

(EI) m/z 310.1745 [(M⁺), calcd for C₂₀H₂₆OSi, 310.1753].

302.2063 [(M⁺), calcd for C₁₉H₃₀OSi, 302.2066]. Spectroscopic data

for anti-S3-o: ¹H NMR (600 MHz, CDCl₃) δ 7.30 (m, 2 H), 7.24 (m,

3 H), 5.78 (m, 2 H), 5.02−4.95 (m, 4 H), 4.41 (dd, J = 5.4, 7.8 Hz,

1 H), 3.55 (dt, J = 1.2, 7.8 Hz, 1 H), 2.52 (m, 1 H), 2.34 (m, 1 H),

0.88 (t, J = 7.8 Hz, 9 H), 0.54 (dq, J = 2.4, 7.8 Hz, 6 H); ¹³C NMR

(126 MHz, CDCl₃) δ 142.2, 138.0, 135.5, 128.1 (2 C), 127.43 (2 C),

127.37, 116.3, 112.8, 79.0, 71.5, 42.9, 7.3, 1.6; IR (ﬁlm) 3064, 2953,

1450, 1011, 910 cm⁻¹; HRMS (EI) m/z 302.2065 [(M⁺), calcd for

C₁₉H₃₀OSi, 302.2066].

syn/anti-Dimethylphenyl(1-((1-phenylbut-3-en-1-yl)oxy)allyl)-

silane (S3-m). Applying general procedure D to S2-b (256 mg,

1.331 mmol, 1 equiv), the trichloroacetimidate of 1-phenylbut-3-en-1-ol

(662 mg, 2.26 mmol, 1.7 equiv), and (TMS)OTf (24 μL, 0.133 mmol,

0.1 equiv) in hexane (7 mL) aﬀorded after column chromatography

(hexanes) a total of 250 mg (58%) of syn/anti-S3-m (1:1) as a colorless

oil. Compounds syn- and anti-S3-m were separable by column chro-

syn/anti-(1-((1-(3-Methoxyphenyl)but-3-en-1-yl)oxy)allyl)-

dimethylphenylsilane (S3-p). Applying general procedure D to S2-b

(1 g, 5.2 mmol, 1 equiv), trichloroacetimidate S1-c (2.68 g, 8.32 mmol,

1.6 equiv), and (TMS)OTf (94 μL, 0.52 mmol, 0.1 equiv) in hexane

(29 mL) aﬀorded after column chromatography (15% CH₂Cl₂in

hexanes) a total of 1.298 g (71%) of syn/anti-S3-p (1:1). Diastereo-

mers were partially separated and obtained as colorless oils. Spectro-

1

matography. Spectroscopic data for syn-S3-m: H NMR (600 MHz,

CDCl₃) δ 7.58 (m, 2 H), 7.35 (m, 3 H), 7.26 (m, 2 H), 7.21 (m, 3 H),

5.65−5.55 (m, 2 H), 4.91−4.87 (m, 3 H), 4.81 (m, 1 H), 4.28 (t, J =

6.0 Hz, 1 H), 3.98 (dt, J = 1.8, 7.2 Hz, 1 H) 2.45 (m, 1 H), 2.35 (m,

1 H), 0.36 (s, 3 H), 0.31 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ

143.3, 137.4, 137.0, 134.7, 134.3 (2 C), 129.2, 127.8 (2 C), 127.6 (2 C),

126.9, 126.6 (2 C), 81.1, 75.2, 41.5, −5.2, −5.5; IR (ﬁlm) 3071, 2961,

1427, 1248, 1115, 837 cm⁻¹; HRMS (EI) m/z 322.1751 [(M⁺), calcd

1

scopic data for syn-S3-p: H NMR (600 MHz, CDCl₃) δ 7.61 (m,

2 H), 7.36 (m, 3 H), 7.19 (t, J = 7.8 Hz, 1 H), 6.85 (d, J = 0.6 Hz,

1 H), 6.81 (dd, J = 0.6, 7.2 Hz, 1 H), 6.76 (ddd, J = 0.6, 2.4, 7.8 Hz,

1 H), 5.70−5.59 (m, 2 H), 4.94 (m, 3 H), 4.86 (dt, J = 10.8 Hz, 1 H),

4.29 (t, J = 6.0 Hz, 1 H), 4.00 (dt, J = 1.2, 7.8 Hz, 1 H), 3.78 (s, 3 H),

2.46 (m, 1 H), 2.37 (m, 1 H), 0.39 (s, 3 H), 0.35 (s, 3 H); ¹³C NMR

(151 MHz, CDCl₃) δ 159.3, 145.0, 137.4, 136.9, 134.7, 134.3 (2 C),

129.2, 128.8, 127.6 (2 C), 119.0, 116.8, 112.5, 112.4, 111.9, 81.0, 75.2,

55.1, 41.6, −5.2, −5.6; IR (ﬁlm) 3071, 2958, 1254, 1046, 837 cm⁻¹;

HRMS (EI) m/z 352.1855 [(M⁺), calcd for C₂₂H₂₈O₂Si, 352.1859].

Spectroscopic data for anti-S3-p: ¹H NMR (600 MHz, CDCl₃) δ 7.52

(m, 2 H), 7.33 (m, 3 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.76 (ddd, J = 0.6,

2.4, 7.8 Hz, 1 H), 6.68 (m, 2 H), 5.80 (ddt, J = 7.2, 10.2, 17.4 Hz,

1 H), 5.69 (ddd, J = 7.2, 10.2, 18.0 Hz, 1 H), 5.03−4.94 (m, 4 H), 4.43

(dd, J = 5.4, 7.8 Hz, 1 H), 3.69 (s, 3 H), 3.66 (dt, J = 1.2, 7.2 Hz, 1 H),

2.51 (m, 1 H), 2.33 (m, 1 H), 0.29 (s, 3 H), 0.27 (s, 3 H).). ¹³C NMR

(151 MHz, CDCl₃) δ 159.5, 143.8, 137.1, 136.8, 135.4, 134.4 (2 C),

129.04, 129.03, 127.4 (2 C), 119.8, 116.4, 113.7, 113.2, 112.2, 79.1,

72.5, 43.0, −5.3, −5.8; IR (ﬁlm) 3071, 2958, 1254, 1046, 837 cm⁻¹;

HRMS (EI) m/z 352.1859 [(M⁺), calcd for C₂₂H₂₈O₂Si, 352.1859].

syn/anti-(1-((1-(4-Chlorophenyl)but-3-en-1-yl)oxy)allyl)-

dimethylphenylsilane (S3-q). Applying general procedure D to S2-b

(1 g, 5.2 mmol, 1 equiv), trichloroacetimidate S1-i (2.72 g, 8.32 mmol,

1.6 equiv), and (TMS)OTf (94 μL, 0.52 mmol, 0.1 equiv) in hexane

(29 mL) aﬀorded after column chromatography (hexanes and 10%

CH₂Cl₂in hexanes) a total of 1.686 g (91%) of syn/anti-S3-q (1:1).

Diastereomers were partially separated and obtained as colorless oils.

1

for C₂₁H₂₆OSi, 322.1753]. Spectroscopic data for anti-S3-m: H NMR

(600 MHz, CDCl₃) δ 7.50 (m, 2 H), 7.36 (m, 1 H), 7.32 (m, 2 H), 7.21

(m, 3 H), 7.06 (m, 2 H), 5.78 (ddt, J = 7.2, 10.2, 17.4 Hz, 1 H), 5.69

(ddd, J = 7.2, 10.8, 17.4 Hz, 1 H), 5.02−4.93 (m, 4 H), 4.43 (dd, J = 5.4,

7.8 Hz, 1 H), 3.60 (d, J = 7.8 Hz, 1 H), 2.50 (quintet, A of ABX system,

J = 7.2 Hz, 1 H), 2.32 (quintet, B of ABX system, J = 7.2 Hz, 1 H), 0.28

(s, 3 H), 0.25 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ 142.1, 137.1,

136.8, 135.4, 134.4 (2 C), 129.0, 128.0 (2 C), 127.4 (2 C), 127.30

(2 C), 127.26, 79.2, 72.5, 43.0, −5.3, −6.0; IR (ﬁlm) 3071, 2961, 1427,

1248, 1115, 837 cm⁻¹; HRMS (EI) m/z 322.1753 [(M⁺), calcd for

C₂₁H₂₆OSi, 322.1753].

syn/anti-Methyldiphenyl(1-((1-phenylbut-3-en-1-yl)oxy)allyl)-

silane (S3-n). Applying general procedure D to S2-c (2.17 g,

8.53 mmol, 1 equiv), the trichloroacetimidate of 1-phenylbut-3-en-1-ol

(5 g, 17.07 mmol, 2 equiv), and (TMS)OTf (230 μL, 1.28 mmol,

0.15 equiv) in cyclohexane (41 mL) aﬀorded after column chromato-

graphy (10% CH₂Cl₂in hexanes) 2.7 g (83%) of syn/anti-S3-n (1:1)

as a colorless oil. Spectroscopic data for syn-S3-n: ¹H NMR

(500 MHz, CDCl₃) δ 7.68 (m, 2 H), 7.59 (m, 2 H), 7.39−7.33 (m,

5 H), 7.27 (m, 3 H), 7.22 (m, 3 H), 5.67 (ddd, J = 7.0, 10.5, 17.5 Hz,

1 H), 5.47 (m, 1 H), 4.93 (dt, J = 2.0, 17.5 Hz, 1 H), 4.85−4.81 (m,

3 H), 4.31 (dt, J = 1.5, 7.0 Hz, 1 H), 4.27 (t, J = 7.0 Hz, 1 H), 2.44 (m,

1 H), 2.31 (m, 1 H), 0.59 (m, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ

143.1, 137.1, 135.4 (2 C), 135.2 (2 C), 134.8, 134.6, 129.4, 129.3,

127.8 (2 C), 127.7 (2 C), 127.6 (2 C), 127.0, 126.7, 81.4, 74.7, 41.5,

−6.5; IR (ﬁlm) 3071, 2975, 1429, 1115, 734 cm⁻¹; HRMS (EI) m/z

384.1901 [(M⁺), calcd for C₂₆H₂₈OSi, 384.1909]. Spectroscopic data

for anti-S3-n: ¹H NMR (500 MHz, CDCl₃) δ 7.63 (m, 2 H), 7.49 (m,

2 H), 7.40 (m, 1 H), 7.37−7.29 (m, 5 H), 7.19 (m, 3 H), 6.97 (m,

2 H), 5.84−5.73 (m, 2 H), 5.05−4.97 (m, 4 H), 4.50 (dd, J = 5.5,

7.5 Hz, 1 H), 3.93 (dt, J = 1.5, 8.0 Hz, 1 H), 2.53 (m, 1 H), 2.35 (m,

1 H), 0.53 (s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 141.6, 136.7,

135.5 (2 C), 135.4, 135.3 (2 C), 135.2, 129.4, 129.2, 128.0 (2 C),

127.54 (2 C), 127.52 (2 C), 127.46 (2 C), 127.3, 116.5, 114.8, 79.2,

72.1, 42.9, −6.6; IR (ﬁlm) 3071, 3976, 1429, 1115, 724 cm⁻¹; HRMS

(EI) m/z 384.1889 [(M⁺), calcd for C₂₆H₂₈OSi, 384.1909].

1

Spectroscopic data for syn-S3-q: H NMR (600 MHz, CDCl₃) δ 7.61

(m, 2 H), 7.40−7.36 (m, 3 H), 7.25 (m, 2 H), 7.18 (m, 2 H), 5.67−

5.55 (m, 2 H), 4.95−4.85 (m, 4 H), 4.29 (t, J = 6.0 Hz, 1 H), 4.00 (dt,

J = 1.2, 5.4 Hz, 1 H), 2.45 (m, 1 H), 2.35 (m, 1 H), 0.39 (s, 3 H), 0.35

(s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ 141.8, 137.2, 136.7, 134.3

(2 C), 134.2, 132.5, 129.2, 128.0 (2 C), 127.9 (2 C), 127.6 (2 C),

117.2, 112.6, 80.4, 75.4, 41.3, −5.3, −5.7; IR (ﬁlm) 3072, 2961, 1490,

1114, 913, 836 cm⁻¹; HRMS (EI) m/z 356.1352 [(M⁺), calcd for

1

C₂₁H₂₅OSiCl, 356.1363]. Spectroscopic data for anti-S3-q: H NMR

(600 MHz, CDCl₃) δ 7.52 (m, 2 H), 7.39 (tt, J = 1.8, 7.8 Hz, 1 H),

7.34 (t, J = 7.2 Hz, 2 H), 7.17 (m, 2 H), 6.95 (m, 2 H), 5.76 (m, 1 H),

5.71 (ddd, J = 7.2, 10.2, 17.4 Hz, 1 H), 5.03 (dt, J = 1.8, 10.8 Hz, 1 H),

5.01−4.96 (m, 3 H), 4.42 (dd, J = 6.0, 7.8 Hz, 1 H), 3.56 (d, J =

7.8 Hz, 1 H), 2.48 (m, 1 H), 2.30 (m, 1 H), 0.31 (s, 3 H), 0.26 (s,

3 H); ¹³C NMR (151 MHz, CDCl₃) δ 140.5, 136.8, 136.6, 134.8,

134.4 (2 C), 132.9, 129.1, 128.6 (2 C), 128.2 (2 C), 127.5 (2 C),

116.8, 113.7, 78.5, 72.7, 42.9, 31.6, 22.7, 14.1, −5.3, −6.3; IR (ﬁlm)

3076, 2961, 1489, 1093, 911, 830 cm⁻¹; HRMS (EI) m/z 356.1355

[(M⁺), calcd for C₂₁H₂₅OSiCl, 356.1363].

syn-(1-((1-(4-Chlorophenyl)but-3-en-1-yl)oxy)allyl)triethylsilane

(S3-r). Applying general procedure D to S2-d (0.73 g, 4.23 mmol, 1

equiv), trichloroacetimidate S1-i (1.8 g, 5.5 mmol, 1.3 equiv), and

(TMS)OTf (76 μL, 0.24 mmol, 0.1 equiv) in hexane (24 mL) aﬀorded

after column chromatography (hexanes and 10% CH₂Cl₂in hexanes) a

total of 0.96 g (ca. 67%) of impure syn/anti-S3-r (1:1). Only com-

pound syn-S3-q was puriﬁed by subsequent column chromatography:

¹H NMR (600 MHz, CDCl₃) δ 7.24 (m, 2 H), 7.19 (m, 2 H), 5.64

syn/anti-Triethyl(1-((1-phenylbut-3-en-1-yl)oxy)allyl)silane (S3-o). Ap-

plying general procedure D to S2-d (583 mg, 3.38 mmol, 1 equiv), the

trichloroacetimidate of 1-phenylbut-3-en-1-ol (1.48 g, 5.07 mmol,

1.5 equiv), and (TMS)OTf (31 μL, 0.169 mmol, 0.05 equiv) in hexane

(19 mL) aﬀorded after column chromatography (hexanes) a total of

720 mg (70%) of syn/anti-S3-o (1:1) as a colorless oil. Compounds

syn- and anti-S3-o were separable by column chromatography. Spec-

1

troscopic data for syn-S3-o: H NMR (500 MHz, CDCl₃) δ 7.26 (m,

4 H), 7.20 (m, 1 H), 5.68 (m, 2 H), 4.98−4.88 (m, 3 H), 4.80 (dd, J =

1.0, 10.0 Hz, 1 H), 4.35 (t, J = 6.0 Hz, 1 H), 3.98 (dd, J = 1.5, 7.5 Hz,

1 H), 2.52 (m, 1 H), 2.42 (m, 1 H), 0.98 (t, J = 8.0 Hz, 9 H), 0.62 (dq,

J = 1.5, 7.5 Hz, 6 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.7, 138.3,

134.8, 127.8 (2 C), 126.8, 126.6 (2 C), 116.8, 111.8, 80.9, 74.3, 41.3,

7.5, 1.8; IR (ﬁlm) 3078, 2953, 1454, 1014, 910 cm⁻¹; HRMS (EI) m/z

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(m, 2 H), 4.96−4.93 (m, 2 H), 4.88 (dt, J = 1.8, 17.4 Hz, 1 H), 4.81

(dt, J = 1.8, 10.8, 1 H), 4.32 (t, J = 6.0 Hz, 1 H), 3.96 (dt, J = 1.2,

7.8 Hz, 1 H), 2.48 (m, 1 H), 2.37 (m, 1 H), 0.97 (t, J = 7.8 Hz, 9 H),

0.61 (dq, J = 3.0, 7.8 Hz, 6 H); ¹³C NMR (151 MHz, CDCl₃) δ 142.2,

138.1, 134.2, 132.4, 127.9 (2 C), 117.2, 112.0, 80.3, 74.6, 41.2, 7.4, 1.7;

IR (ﬁlm) 3033, 2957, 1491, 833 cm⁻¹; HRMS (EI) m/z 336.1663

[(M⁺), calcd for C₁₉H₂₉OSiCl, 336.1676].

(m, 2 H), 2.48 (m, 1 H), 2.34 (m, 1 H), 1.63 (m, 3 H), 1.51 (m, 3 H),

0.07 (s, 9 H), −0.02 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 145.0,

144.4, 143.4, 142.3, 135.5, 134.6, 128.1 (2 C), 127.8 (2 C), 127.5

(2 C), 127.4, 126.8, 126.6 (2 C), 116.9, 116.4, 109.9, 109.5, 80.0, 79.0,

77.8, 75.4, 43.0, 40.5, 20.4, 20.3, −3.0, −3.2; IR (ﬁlm) 3072, 2959,

1248, 1060, 839 cm⁻¹; HRMS (EI) m/z 274.1753 [(M⁺), calcd for

C₁₇H₂₆OSi, 274.1753].

syn/anti-Triethyl(1-((1-(naphthalen-2-yl)but-3-en-1-yl)oxy)allyl)-

silane (S3-s). Applying general procedure D to S2-d (860 mg, 5 mmol,

1 equiv), trichloroacetimidate S1-l (2.4 g, 7 mmol, 1.4 equiv), and

(TMS)OTf (22.5 μL, 0.125 mmol, 0.025 equiv) in hexane (28 mL)

aﬀorded after column chromatography (hexanes and 10% CH₂Cl₂in

hexanes) a total of 793 mg (45%) of syn/anti-S3-s (1:1). Diastereo-

mers were partially separated and obtained as colorless oils. Spectro-

syn/anti-(1-((1-(4-Methoxyphenyl)but-3-en-1-yl)oxy)-2-

methylallyl)trimethylsilane (S3-v). Applying general procedure D to

S2-e (660 mg, 79% (w/w) in THF, 3.6 mmol, 1 equiv), trichloro-

acetimidate S1-d (1.86 g, 5.77 mmol, 1.6 equiv), and (TMS)OTf

(0.32 μL, 0.18 mmol, 0.05 equiv) in hexane (20 mL) aﬀorded after

column chromatography (15% and 20% CH₂Cl₂in hexanes) a total of

918 mg (83%) of syn/anti-S3-v (1:1) as a colorless oil. Compounds

syn- and anti-S3-v were separable by column chromatography. Spectro-

1

scopic data for syn-S3-s: H NMR (500 MHz, CDCl₃) δ 7.84 (m,

1

scopic data for syn-S3-v: H NMR (500 MHz, CDCl₃) δ 7.20 (m,

2 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.74 (s, 1 H), 7.47 (m, 3 H), 5.74 (m,

2 H), 5.04−4.95 (m, 3 H), 4.82 (m, 1 H), 4.55 (d, J = 6.0 Hz, 1 H),

4.08 (dt, J = 1.0, 7.0 Hz, 1 H), 2.65 (m, 1 H), 2.54 (m, 1 H), 1.05 (t,

J = 8.0 Hz, 9 H), 0.69 (dq, J = 2.0, 8.0 Hz, 6 H); ¹³C NMR (151 MHz,

CDCl₃) δ 141.2, 138.3, 134.7, 133.1, 132.7, 127.9, 127.7, 127.5, 125.7,

125.4, 125.3, 125.0, 116.9, 111.9, 81.2, 74.6, 41.4, 7.5, 1.8; IR (ﬁlm)

3057, 2953, 2878, 1414, 1018, 910, 817 cm⁻¹; HRMS (EI) m/z

352.2210 [(M⁺), calcd for C₂₃H₃₂OSi, 352.2222]. Spectroscopic data

2 H), 6.81 (m, 2 H), 5.66 (ddt, J = 7.2, 10.2, 17.4 Hz, 1 H), 4.98−4.93

(m, 2 H), 4.67 (m, 1 H), 4.65 (m, 1 H), 4.27 (t, J = 6.6 Hz, 1 H), 3.78

(s, 3 H), 3.75 (s, 1 H), 2.52 (m, 1 H), 2.43 (m, 1 H), 0.06 (s, 9 H);

¹³C NMR (151 MHz, CDCl₃) δ 158.4, 145.1, 135.5, 134.8, 127.7

(2 C), 116.8, 113.1 (2 C), 109.3, 79.8, 77.7, 55.1, 40.5, 20.3, −2.9; IR

(ﬁlm) 3033, 2950, 1238, 840 cm⁻¹; HRMS (EI) m/z 304.1853 [(M⁺),

1

calcd for C₁₈H₂₈O₂Si, 304.1859]. Spectroscopic data for anti-S3-v: H

1

for anti-S3-s: H NMR (500 MHz, CDCl₃) δ 7.80 (m, 3 H), 7.63 (s,

NMR (600 MHz, CDCl₃) δ 7.15 (d, J = 8.4 Hz, 2 H), 6.85 (d, J =

8.4 Hz, 2 H), 5.78 (ddt, J = 6.6, 9.6, 16.8 Hz, 1 H), 4.99−4.94 (m,

2 H), 4.80 (s, 1 H), 4.66 (s, 1 H), 4.23 (t, J = 7.2 Hz, 1 H), 3.80 (s,

3 H), 3.30 (s, 1 H), 2.53 (m, 1 H), 2.33 (m, 1 H), −0.02 (s, 9 H); ¹³C

NMR (151 MHz, CDCl₃) δ 158.9, 144.5, 135.6, 134.3, 128.7 (2 C),

116.3, 113.4 (2 C), 109.8, 78.5, 75.0, 55.1, 43.0, 20.4, −3.2; IR (ﬁlm)

3074, 2955, 1247, 824 cm⁻¹; HRMS (EI) m/z 304.1859 [(M⁺), calcd

for C₁₈H₂₈O₂Si, 304.1859].

1 H), 7.46−7.41 (m, 3 H), 5.79 (m, 2 H), 5.04−4.94 (m, 4 H), 4.59

(dd, J = 6.0, 8.0 Hz, 1 H), 3.58 (d, J = 8.0 Hz, 1 H), 2.60 (m, 1 H),

2.41 (m, 1 H), 0.88 (t, J = 8.0 Hz, 9 H), 0.55 (dq, J = 4.0, 8.0 Hz,

6 H); ¹³C NMR (151 MHz, CDCl₃) δ 139.7, 138.0, 135.4, 133.1,

133.09, 128.0, 127.8, 127.7, 126.6, 125.9, 125.6, 125.1, 116.5, 112.9,

79.1, 71.6, 42.9, 7.4, 1.6; IR (ﬁlm) 3059, 2953, 2876, 1458, 1020,

910 cm⁻¹; HRMS (EI) m/z 352.2222 [(M⁺), calcd for C₂₃H₃₂OSi,

352.2222].

syn/anti-Trimethyl(2-methyl-1-((1-(4-methylphenyl)but-3-en-1-

yl)oxy)allyl)silane (S3-w). Applying general procedure D to S2-e

(380 mg, 79% (w/w) in THF, 2.083 mmol, 1 equiv), trichloro-

acetimidate S1-g (1.02 g, 3.33 mmol, 1.6 equiv), and (TMS)OTf

(19 μL, 0.104 mmol, 0.05 equiv) in hexane (12 mL) aﬀorded after

column chromatography (2% CH₂Cl₂in hexanes) a total of 390 mg

(61%) of syn/anti-S3-w (1:1) as a colorless oil: mixture of diastereo-

syn/anti-Trimethyl(1-((1-(2-propylphenyl)but-3-en-1-yl)oxy)allyl)-

silane (S3-t). Applying general procedure D to α-(trimethylsilyl)allyl

alcohol (380 mg, 69.6% (w/w) in THF, 2.03 mmol, 1 equiv), trichlo-

roacetimidate S1-t (679 mg, 2.03 mmol, 1 equiv), and (TMS)OTf

(37 μL, 0.2 mmol, 0.1 equiv) in hexane (11 mL) aﬀorded after column

chromatography (hexanes) a total of 144.5 mg (24%) of syn/anti-S3-t

(1:1) as a colorless oil. Compounds syn- and anti-S3-t were separable

by column chromatography. Spectroscopic data for syn-S3-t: ¹H NMR

(500 MHz, CDCl₃) δ 7.45 (m, 1 H), 7.15 (m, 2 H), 7.07 (m, 1 H),

5.80 (ddt, J = 7.0, 10.0, 17.0 Hz, 1 H), 5.61 (ddd, J = 7.5, 10.5,

17.5 Hz, 1 H), 5.03−4.97 (m, 2 H), 4.87 (dt, J = 2.0, 17.5 Hz, 1 H),

4.79 (ddd, J = 1.5, 2.0, 10.5 Hz, 1 H), 4.58 (dd, J = 5.0, 7.5 Hz, 1 H),

3.78 (dt, J = 1.5, 7.5 Hz, 1 H), 2.53 (m, 2 H), 2.46 (m, 1 H), 2.36 (m,

1 H), 1.59 (m, 2 H), 0.96 (t, J = 7.5 Hz, 3 H), 0.05 (s, 9 H); ¹³C NMR

(126 MHz, CDCl₃) δ 141.6, 138.5, 138.1, 135.4, 128.8, 126.9, 126.6,

125.6, 116.6, 111.8, 77.9, 76.6, 42.1, 34.5, 24.2, 14.2, −3.8; IR (ﬁlm)

3074, 2959, 1248, 841 cm⁻¹; HRMS (EI) m/z 302.2078 [(M⁺), calcd

1

mers (syn:anti-S3-w = 1.4:1.0); H NMR (600 MHz, CDCl₃) δ 7.18

(d, J = 8.4 Hz, 2.8 H), 7.13 (s, 4 H), 7.09 (d, J = 7.8 Hz, 2.8 H), 5.81

(ddt, J = 7.2, 10.2, 17.4 Hz, 1 H), 5.68 (ddt, J = 6.6, 9.6, 16.8 Hz,

1.4 H), 5.01−4.94 (m, 4.8 H), 4.81 (m, 1 H), 4.69 (m, 1 H), 4.67 (m,

2.8 H), 4.31 (t, J = 5.4 Hz, 1.4 H), 4.27 (t, J = 6.6 Hz, 1 H), 3.78 (s,

1.4 H), 3.33 (s, 1 H), 2.53 (m, 2.4 H), 2.46 (m, 1.4 H), 2.35 (s, 3 H),

2.34 (heavily overlapped, m, 1 H), 2.33 (s, 4.2 H), 1.64 (d, J = 0.6 Hz,

3 H), 1.53 (d, J = 0.6 Hz, 4.2 H), 0.07 (s, 12.6 H), −0.08 (s, 9 H); ¹³C

NMR (151 MHz, CDCl₃) (syn-S3-v, major) δ 145.0, 140.4, 136.2,

134.8, 128.5 (2C), 126.5 (2C), 116.8, 109.4, 79.8, 77.6, 40.5, 21.1,

20.3, −3.0; (anti-S3-w, minor) δ 144.4, 139.3, 136.9, 135.7, 128.8

(2 C), 127.5 (2 C), 116.3, 109.8, 78.8, 75.2, 43.1, 21.2, 20.4, −3.2; IR

(ﬁlm) 3075, 2957, 1247, 840 cm⁻¹; HRMS (EI) m/z 288.1895 [(M⁺),

calcd for C₁₈H₂₈OSi, 288.1909].

syn/anti-Trimethyl(1-((1-phenylbut-3-en-1-yl)oxy)but-2-yn-1-yl)-

silane (S3-x). Applying general procedure E to compound S2-g (1 g,

4.66 mmol, 1 equiv), benzaldehyde (544 mg, 5.13 mmol, 1.1 equiv),

allyltrimethylsilane (586 mg, 5.13 mmol, 1.1 equiv), and (TMS)OTf

(170 μL, 0.932 mmol, 0.2 equiv) in CH₂Cl₂(47 mL) for 1 h at −78 °C

aﬀorded after workup and column chromatography (1% EtOAc in

hexanes) 1.08 g (90%) of a mixture of anti/syn-S3-x (1.6:1) as a yellow

oil. Compounds anti- and syn-S3-x were partially separated by column

chromatography. Spectroscopic data for syn-S3-x: ¹H NMR (500 MHz,

CDCl₃) δ 7.35−7.28 (m, 4 H), 7.21 (tt, J = 1.5, 7 Hz, 1 H), 5.72 (dddd,

J = 7, 10, 14, 17 Hz, 1 H), 4.98 (m, 2 H), 4.56 (t, J = 6 Hz, 1 H), 3.86

(q, J = 2.5 Hz, 1 H), 2.57−2.44 (m, 2 H), 1.70 (d, J = 3 Hz, 3 H), 0.12

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.1, 134.6, 127.8, 126.9,

126.7, 116.9, 83.4, 81.1, 77.6, 62.3, 40.7, 3.7, −3.7; IR (neat) 3072, 3030,

2959, 2363, 2335, 1641, 1452, 1248, 1057, 843 cm⁻¹; HRMS (EI) m/z

272.1594 [(M⁺), calcd for C₁₇H₂₄OSi, 272.1596]. Spectroscopic data for

anti-S3-x: ¹H NMR (500 MHz, CDCl₃) δ 7.30 (m, 2 H), 7.25 (m, 3 H),

5.75 (dddd, J = 7, 10.5, 14, 17.5 Hz, 1 H), 5.01−4.93 (m, 2 H), 4.67

1

for C₁₉H₃₀OSi, 302.2066]. Spectroscopic data for anti-S3-t: H NMR

(500 MHz, CDCl₃) δ 7.41 (dd, J = 1.5, 7.5 Hz, 1 H), 7.18 (m, 2 H),

7.10 (m, 1 H), 5.92 (m, 1 H), 5.76 (ddd, J = 7.5, 11.0, 17.5 Hz, 1 H),

5.06−4.96 (m, 4 H), 4.78 (dd, J = 4.5, 9.0 Hz, 1 H), 3.39 (dt, J = 1.0,

7.0 Hz, 1 H), 2.53 (m, 2 H), 2.47 (m, 1 H), 2.28 (m, 1 H), 1.55 (m,

2 H), 0.95 (t, J = 7.0 Hz, 3 H), 0.00 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 140.6, 140.4, 138.1, 135.9, 129.1, 126.8, 126.7, 126.0, 116.1,

112.8, 74.4 72.8, 43.2, 34.5, 24.6, 14.2, −4.0; IR (ﬁlm) 3076, 2959,

1248, 841 cm⁻¹; HRMS (EI) m/z 302.2080 [(M⁺), calcd for

C₁₉H₃₀OSi, 302.2066].

syn/anti-Trimethyl(2-methyl-1-((1-phenylbut-3-en-1-yl)oxy)allyl)-

silane (S3-u). Applying general procedure D to S2-e (2.6 g, 76.9%

(w/w) in THF, 13.86 mmol, 1 equiv), the trichloroacetimidate of

1-phenylbut-3-en-1-ol (7.3 g, 24.95 mmol, 1.8 equiv), and (TMS)OTf

(0.25 mL, 1.386 mmol, 0.1 equiv) in hexane (70 mL) aﬀorded after

column chromatography (hexanes) a total of 1.67 g (44%) of syn/anti-

S3-u (1:1) as a colorless oil: mixture of diastereomers (syn:anti-S3-u =

1:1); ¹H NMR (500 MHz, CDCl₃) δ 7.37−7.19 (m, 10 H), 5.81 (ddt,

J = 7.0, 10.5, 17.0 Hz, 1 H), 5.67 (ddt, J = 7.0, 10.5, 17.0 Hz, 1 H),

5.00−4.93 (m, 3 H), 4.80 (m, 1 H), 4.66 (m, 2 H), 4.32 (t, J = 6.0 Hz,

1 H), 4.28 (dd, J = 6.0, 8.0 Hz, 1 H), 3.77 (s, 1 H), 3.31 (s, 1 H), 2.52

O

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(t, J = 7 Hz, 1 H), 3.45 (q, J = 2.5 Hz, 1 H), 2.54 (m, 1 H), 2. 36 (m,

1 H), 1.87 (d, J = 2.5 Hz, 3 H), 0.05 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 141.8, 135.2, 128.1, 127.4, 127.3, 116.2, 82.8, 79.8, 77.3, 60.3,

42.6, 3.9, −4; IR (neat) 3076, 2959, 2361, 2336, 1653, 1539, 1456, 1248,

844 cm⁻¹; HRMS (EI) m/z 272.1590 [(M⁺), calcd for C₁₇H₂₄OSi,

272.1596].

5.07−4.96 (m, 3 H), 4.89 (dt, J = 1.5, 10.5 Hz, 1 H), 4.64 (t, J =

6.0 Hz, 1 H), 3.83 (dt, J = 1.5, 7.0 Hz, 1 H), 2.63−2.50 (m, 2 H), 0.04

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 147.6, 137.5, 134.3, 126.1,

124.0, 123.6, 117.3, 112.3, 76.5, 75.7, 41.4, −3.86; IR (neat) 3076,

2957, 1248, 1062, 912, 841 cm⁻¹; HRMS (EI) m/z 266.1148 [(M⁺),

calcd for C₁₄H₂₂OSiS, 266.1161]. Spectroscopic data for anti-S3-aa:

¹H NMR (500 MHz, CDCl₃) δ 7.23 (m, 1 H), 6.92 (dd, J = 3.5,

syn/anti-Trimethyl(1-((3-methyl-1-phenylbut-3-en-1-yl)oxy)allyl)-

silane (S3-y). Applying general procedure D to α-(trimethylsilyl)allyl

alcohol (1.5 g, 44% (w/w) in THF, 5.07 mmol, 1 equiv), the trichlo-

roacetimidate of 3-methyl-1-phenylbut-3-en-1-ol (2.49 g, 8.11 mmol,

1.6 equiv), and (TMS)OTf (47 μL, 0.5 mmol, 0.1 equiv) in hexane

(28 mL) aﬀorded after column chromatography (2% CH₂Cl₂in

hexanes) a total of 847 mg (61%) of syn/anti-S3-y (1:1) as a colorless

oil. Compounds syn- and anti-S3-y were separable by column chro-

5.0 Hz, 1 H), 6.87 (m, 1 H), 5.79 (dddd, J = 7.0, 10.0, 14.0, 17.0 Hz,

1 H), 5.71 (ddd, J = 7.5, 10.5, 17.5 Hz, 1 H), 5.04 (m, 1 H), 5.01 (m

2 H), 4.98 (m, 1 H), 4.69 (t, J = 7.0 Hz, 1 H), 3.56 (dt, J = 1.5, 7.5 Hz,

1 H), 2.61 (m, 1 H), 2.45 (m, 1 H) −0.03 (s, 9 H); ¹³C NMR (126

MHz, CDCl₃) δ 146.5, 137.4, 134.9, 126.0, 125.5, 124.8, 116.8, 113.1,

74.7, 72.8, 43.4, −4.0; IR (neat) 3076, 2957, 1248, 914, 843 cm⁻¹;

HRMS (EI) m/z 266.1153 [(M⁺), calcd for C₁₄H₂₂OSiS, 266.1161].

syn/anti-(1-((1-(Furan-2-yl)but-3-en-1-yl)oxy)allyl)trimethylsilane

(S3-bb). Applying general procedure D to α-(trimethylsilyl)allyl

alcohol (990 mg, 77.4% (w/w) in THF, 5.9 mmol, 1 equiv), trichloro-

acetimidate S1-bb (2.17 g, 7.67 mmol, 1.3 equiv), and (TMS)OTf

(27 μL, 0.147 mmol, 0.025 equiv) in hexane (33 mL) aﬀorded after

column chromatography (hexanes) a total of 720 mg (49%) of syn/

anti-S3-bb (1:1) as a colorless oil. Compounds syn- and anti-S3-bb

were separable by column chromatography. Spectroscopic data for syn-

1

matography. Spectroscopic data for syn-S3-y: H NMR (500 MHz,

CDCl₃) δ 7.26 (m, 4 H), 7.19 (m, 1 H), 5.62 (ddd, J = 7.0, 10.5,

17.0 Hz, 1 H), 4.88 (m, 1 H), 4.79 (m, 1 H), 4.70 (m, 1 H), 4.60 (m,

1 H), 4.41 (t, J = 6.5 Hz, 1 H), 3.76 (dt, J = 1.5, 7.0 Hz, 1 H), 2.52 (dd,

A of ABX system, J = 7.0, 14.0 Hz, 1 H), 2.26 (dd, B of ABX system,

J = 6.5, 14.0 Hz, 1 H), 1.67 (s, 3 H), 0.02 (s, 9 H); IR (ﬁlm) 3065,

2957, 1245, 841 cm⁻¹; HRMS (EI) m/z 274.1741 [(M⁺), calcd for

C₁₇H₂₆OSi, 274.1753]. Spectroscopic data for anti-S3-y: ¹H NMR

(500 MHz, CDCl₃) δ 7.34 (m, 2 H), 7.28 (m, 3 H), 5.76 (ddd, J = 7.5,

10.5, 17.5 Hz, 1 H), 5.06 (dq, J = 1.0, 10.0 Hz, 1 H), 4.99 (dt, J = 1.5,

17.5 Hz, 1 H), 4.75 (m, 1 H), 4.67 (m, 1 H), 4.55 (dd, J = 6.0, 8.0 Hz,

1 H), 3.42 (dt, J = 1.0, 7.5 Hz, 1 H), 2.52 (dd, A of ABX system, J =

8.0, 13.5 Hz, 1 H), 2.29 (dd, B of ABX system, J = 5.0, 13.5 Hz, 1 H),

1.76 (s, 3 H), 0.00 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.0,

142.8, 137.5, 128.0 (2 C), 127.3 (2 C), 127.27, 113.0, 112.6, 78.7, 72.8,

47.0, 23.3, −4.0; IR (ﬁlm) 3076, 2959, 1247, 840 cm⁻¹; HRMS (EI)

m/z 274.1745 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

1

S3-bb: H NMR (500 MHz, CDCl₃) δ 7.32 (m, 1H), 6.27 (ddd, J =

0.5, 2.0, 3.0 Hz, 1 H), 6.19 (m, 1 H), 5.75 (dddd, J = 7.0, 10.5, 14.0,

17.5 Hz, 1 H), 5.69 (ddd, J = 7.0, 10.5, 17.0 Hz, 1 H), 5.04 (ddt, J =

1.5, 2.0, 17.0 Hz, 1 H), 4.99 (m, 1 H), 4.92 (ddd, J = 1.5, 2.0, 17.5 Hz,

1 H), 4.83 (ddd, J = 1.0, 2.0, 11.0 Hz, 1 H), 4.33 (t, J = 6.5 Hz, 1 H),

3.73 (dt, J = 1.5, 7.0 Hz, 1 H), 2.64−2.52 (m, 2 H), 0.01 (s, 9 H); ¹³C

NMR (126 MHz, CDCl₃) δ 155.5, 141.4, 137.6, 134.5, 117.0, 111.4,

109.9, 107.2, 76.0, 75.1, 38.0, −3.89; IR (neat) 3078, 2959, 1248,

841 cm⁻¹; HRMS (EI) m/z 250.1381 [(M⁺), calcd for C₁₄H₂₂O₂Si,

1

syn/anti-Trimethyl(1-((3-methyl-1-(4-methylphenyl)but-3-en-1-

yl)oxy)allyl)silane (S3-z). Applying general procedure D to α-(tri-

methylsilyl)allyl alcohol (0.97 g, 85.5% (w/w) in THF, 6.35 mmol,

1 equiv), trichloroacetimidate S1-z (2.85 g, 8.89 mmol, 1.4 equiv),

and (TMS)OTf (57 μL, 0.317 mmol, 0.05 equiv) in hexane (35 mL)

aﬀorded after column chromatography (5% and 30% CH₂Cl₂in

hexanes) a total of 1.2 g (65%) of syn/anti-S3-z (1:1) as a colorless oil.

Compounds syn- and anti-S3-z were separable by column chromatog-

raphy. Spectroscopic data for syn-S3-z: ¹H NMR (500 MHz, CDCl₃) δ

7.16 (d, J = 7.0 Hz, 2 H), 7.07 (d, J = 7.5 Hz, 2 H), 5.64 (dddd, J = 1.0,

7.0, 10.5, 17.0 Hz, 1 H), 4.90 (dq, J = 1.5, 17.0 Hz, 1 H), 4. 80 (m, 1

H), 4.70 (m, 1 H), 4.61 (m, 1 H), 4.39 (t, J = 7.0 Hz, 1 H), 3.75 (dt,

J = 1.5, 7.0 Hz, 1 H), 2.51 (dd, A of ABX system, J = 7.0, 14.0 Hz,

1 H), 2.31 (s, 3 H), 2.25 (dd, B of ABX system, J = 6.5, 13.5 Hz, 1 H),

1.67 (d, J = 1.0 Hz, 3 H), 0.02 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃)

δ 142.6, 141.0, 138.2, 136.4, 128.5 (2 C), 126.6 (2 C), 113.0, 111.6,

80.5, 76.0, 46.1, 23.1, 21.1, −3.7; IR (ﬁlm) 3079, 2961, 1248, 1060,

841 cm⁻¹; HRMS (EI) m/z 288.1900 [(M⁺), calcd for C₁₈H₂₈OSi,

288.1909]. Spectroscopic data for anti-S3-z: ¹H NMR (500 MHz,

CDCl₃) δ 7.11 (m, 4 H), 5.72 (ddd, J = 8.0, 11.0, 17.5 Hz, 1 H),

5.00 (ddd, J = 1.0, 2.0, 10.5 Hz, 1 H), 4.95 (ddd, J = 1.0, 2.0, 17.0 Hz,

1 H), 4.71 (m, 1 H), 4.64 (m, 1 H), 4.49 (dd, J = 5.0, 8.0 Hz, 1 H),

3.39 (dt, J = 1.0, 7.5 Hz, 1 H), 2.46 (dd, A of ABX system, J = 9.0,

13.5 Hz, 1 H), 2.33 (s, 3 H), 2.23 (dd, B of ABX system, J = 5.5,

14.0 Hz, 1 H), 1.72 (m, 3 H), −0.04 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 143.2, 139.7, 137.6, 136.8, 128.8 (2 C), 127.2 (2 C), 112.9,

112.5, 78.4, 72.6, 47.0, 23.3, 21.2, −4.0; IR (ﬁlm) 3076, 2961, 1248,

1053, 841 cm⁻¹; HRMS (EI) m/z 288.1909 [(M⁺), calcd for

C₁₈H₂₈OSi, 288.1909].

250.1389]. Spectroscopic data for anti-S3-bb: H NMR (500 MHz,

CDCl₃) δ 7.35 (m, 1 H), 6.29 (dd, J = 2.0, 3.0 Hz, 1 H), 6.17 (dd, J =

1.0, 3.5 Hz, 1 H), 5.75 (m, 2 H), 5.05−4.95 (m, 4 H), 4.40 (t, J =

7.0 Hz, 1 H), 3.51 (dt, J = 1.5, 7.0 Hz, 1 H), 2.60 (m, 1 H), 2.52 (m,

1 H), −0.07 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 154.8, 141.9,

137.3, 134.7, 116.7, 112.4, 109.7, 108.0, 73.1, 72.7, 39.4, −4.2; IR

(neat) 3078, 2957, 1248, 841 cm⁻¹; HRMS (EI) m/z 250.1379 [(M⁺),

calcd for C₁₄H₂₂O₂Si, 250.1389].

syn/anti-(1-((1-(4-Bromophenyl)but-3-en-1-yl)oxy)allyl)-

trimethylsilane (S3-cc). Applying general procedure D to α-(trimeth-

ylsilyl)allyl alcohol (2.3 g, solution 44% (w/w) in THF, 11.51 mmol,

1 equiv), trichloroacetimidate S1-cc (6.8 g, 18.4 mmol, 1.6 equiv), and

(TMS)OTf (208 μL, 1.151 mmol, 0.1 equiv) in hexane (64 mL)

aﬀorded after column chromatography (hexanes) 1.425 g (37%) of

syn/anti-S3-cc (1:1) as a colorless oil: mixture of diastereomers

(syn:anti-S3-cc = 1:1); ¹H NMR (600 MHz, CDCl₃) δ 7.42 (m, 2 H),

7.39 (m, 2 H), 7.14 (m, 2 H), 7.10 (m, 2 H), 5.76−5.59 (m, 4 H),

5.01−4.93 (m, 6 H), 4.87 (dt, J = 1.8, 16.8 Hz, 1 H), 4.83 (dt, J = 1.8,

10.8 Hz, 1 H), 4.38 (dd, J = 6.0, 7.8 Hz, 1 H), 4.32 (t, J = 6.0 Hz, 1 H),

3.77 (dt, J = 1.8, 7.2 Hz, 1 H), 3.35 (dt, J = 1.1, 7.8 Hz, 1 H), 2.49 (m,

2 H), 2.40 (m, 1 H), 2.35 (m, 1 H), 0.03 (s, 9 H), −0.04 (s, 9 H); ¹³C

NMR (126 MHz, CDCl₃) δ 142.6, 141.5, 137.6, 137.3, 134.8, 134.2,

131.3 (2 C), 131.0 (2 C), 129.1 (2 C), 128.3 (2 C), 121.1, 120.6,

117.3, 116.8, 113.1, 112.1, 80.3, 78.6, 76.0, 73.1, 42.8, 41.3, −3.8, −4.0;

IR (ﬁlm) 3078, 2957, 1487, 1246, 1070, 1010, 841 cm⁻¹; HRMS (EI)

m/z 338.0712 [(M⁺), calcd for C₁₆H₂₃OSiBr, 338.0702].

Synthesis of Cyclic Ethers 1 and 2. trans-Trimethyl(6-phenyl-

5,6-dihydro-2H-pyran-2-yl)silane (1a).¹⁴Applying general procedure

F to syn-S3-a (184 mg, 0.707 mmol) and Grubbs second-generation

catalyst (24 mg, 0.028 mmol, 0.04 equiv) in CH₂Cl₂for 3 h followed

by column chromatography (30% CH₂Cl₂in hexanes) aﬀorded 151

syn/anti-Trimethyl(1-((1-(thiophene-2-yl)but-3-en-1-yl)oxy)allyl)-

silane (S3-aa). Applying general procedure D to α-(trimethylsilyl)allyl

alcohol (1.03 g, 77.4% (w/w) in THF, 6.14 mmol, 1 equiv), trichloro-

acetimidate S1-aa (2.75 g, 9.21 mmol, 1.5 equiv), and (TMS)OTf

(55.5 μL, 0.307 mmol, 0.05 equiv) in hexane (34 mL) aﬀorded after

column chromatography (hexanes) a total of 982 mg (60%) of syn/

anti-S3-aa (1:1) as a colorless oil. Compounds syn- and anti-S3-aa

were separable by column chromatography. Spectroscopic data for syn-

S3-aa: ¹H NMR (500 MHz, CDCl₃) δ 7.18 (dd, J = 1.0, 5.0 Hz, 1 H),

6.91 (dd, J = 3.0, 5.0 Hz, 1 H), 6.86 (m, 1 H), 5.80−5.70 (m, 2 H),

1

mg (92%) of 1a as a colorless oil: H NMR (500 MHz, CDCl₃) δ

7.38−7.24 (m, 5 H), 5.83−5.76 (m, 2 H), 4.72 (t, J = 5.5 Hz, 1 H),

4.01 (m, 1 H), 2.41−2.38 (m, 2 H), 0.09 (s, 9 H); ¹³C NMR (126

MHz, CDCl₃) δ 142.3, 128.5 (2C), 128.4, 127.5, 126.9 (2C), 120.3,

72.6, 70.4, 30.4, −2.7; HRMS (CI) m/z 261.1664 [(M + H)⁺, calcd for

C₁₆H₂₄OSi, 261.1675]. The relative stereochemistry of 1a was con-

ﬁrmed on the basis of negative NOESY signals between protons at

4.72 and 4.01 ppm.

P

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

cis-Trimethyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane (2a).¹⁴

Following general procedure F, to anti-S3-a (167 mg, 0.641 mmol)

in CH₂Cl₂(10 mL, ∼0.7 M) was added Grubbs second-generation

catalyst (21.4 mg, 0.025 mmol, 0.04 equiv), and the solution was

stirred under nitrogen at room temperature for 3 h. The reaction

mixture was concentrated and puriﬁed by column chromatography

(10% CH₂Cl₂in hexanes) to aﬀord 144 mg (97%) of 2a as a colorless

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 158.8, 134.2, 128.1, 127.9,

120.0, 113.6, 71.9, 69.6, 55.2, 30.0, −3.0; IR (ﬁlm) 1513, 1248, 1038,

840 cm⁻¹; HRMS (EI) m/z 262.1403 [(M⁺), calcd for C₁₅H₂₂O₂Si,

262.1389].

cis-(6-(4-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (2d). Applying general procedure F to anti-S3-d

(149 mg, 0.513 mmol, 1 equiv) and second-generation Grubbs catalyst

(17.4 mg, 0.021 mmol, 0.04 equiv) in CH₂Cl₂(6 mL) for 3 h aﬀorded

after column chromatography (25% CH₂Cl₂in hexanes) 122 mg

1

oil: H NMR (500 MHz, CDCl₃) δ 7.34−7.22 (m, 5 H), 5.82−5.78

(m, 2 H), 4.38 (dd, J = 3.5, 10 Hz, 1 H), 4.17−4.15 (m, 1 H), 2.26−

2.12 (m, 2 H), 0.08 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 144.0,

128.10 (2C), 128.06, 126.9, 125.6 (2C), 121.1, 75.3, 71.6, 34.2,

−4.0; HRMS (CI) m/z 261.1681 [(M + H)⁺, calcd for C₁₆H₂₄OSi,

261.1675]. The relative stereochemistry of 2a was assigned on the

basis of positive NOESY signals between protons at 4.15 and 2.26−

2.12 ppm.

1

(91%) of 2d as a colorless oil: H NMR (500 MHz, CDCl₃) δ 7.27

(m, 2 H), 6.87 (m, 2 H), 5.79 (m, 2 H), 4.34 (dd, J = 4.0, 9.0 Hz,

1 H), 4.16 (m, 1 H), 3.79 (s, 3 H), 2.18 (m, 2 H), 0.08 (s, 9 H); ¹³C

NMR (126 MHz, CDCl₃) δ 158.7, 136.3, 128.1, 126.9, 121.2, 113.5,

75.0, 71.7, 55.2, 34.1, −4.0; IR (ﬁlm) 1248, 1072, 1039, 841 cm⁻¹;

HRMS (EI) m/z 262.1390 [(M⁺), calcd for C₁₅H₂₂O₂Si, 262.1389].

trans-Trimethyl(6-(2-methylphenyl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1e) and cis-Trimethyl(6-(2-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (2e). Applying general procedure F to syn/anti-S3-e

(2:1 ratio, 234 mg, 0.8526 mmol, 1 equiv) and second-generation

Grubbs catalyst (29 mg, 0.034 mmol, 0.04 equiv) in CH₂Cl₂(9 mL)

for 3 h aﬀorded after column chromatography (15% CH₂Cl₂in hex-

anes and 5% EtOAc in hexanes) 114 mg (62%) of 1e and 79 mg

trans-(6-(2-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1b) and cis-(6-(2-Methoxyphenyl)-5,6-dihydro-2H-

pyran-2-yl)trimethylsilane (2b). Applying general procedure F to

syn/anti-S3-b (2:1 ratio, 280 mg, 0.964 mmol, 1 equiv) and second-

generation Grubbs catalyst (33 mg, 0.039 mmol, 0.04 equiv) in

CH₂Cl₂(10 mL) for 3 h aﬀorded after column chromatography (25%

CH₂Cl₂in hexanes and 7% EtOAc in hexanes) 153 mg (62%) of 1b

and 82 mg (31%) of 2b as colorless oils. Spectroscopic data for 1b: ¹H

NMR (600 MHz, CDCl₃) δ 7.42 (dd, J = 1.8, 7.8 Hz, 1 H), 7.23 (t, J =

8.4 Hz, 1 H), 6.95 (tt, J = 0.6, 7.2 Hz, 1 H), 6.85, (d, J = 8.4 Hz, 1 H),

5.82 (m, 2 H), 5.02 (dd, J = 4.2, 8.4 Hz, 1 H), 4.14 (m, 1 H), 3.81 (s,

3 H), 2.29 (m, 2 H), 0.09 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ

156.5, 131.0, 128.2, 127.8, 127.0, 120.9, 120.6, 110.3, 72.3, 67.0, 55.3,

30.7, −2.7; IR (ﬁlm) 1493, 1248, 1049, 839 cm⁻¹; HRMS (EI) m/z

262.1388 [(M⁺), calcd for C₁₅H₂₂O₂Si, 262.1389]. Spectroscopic data

for 2b: ¹H NMR (600 MHz, CDCl₃) δ 7.47 (dd, J = 1.8, 7.8 Hz, 1 H),

7.21 (dt, J = 1.8, 7.8 Hz, 1 H), 6.98 (dt, J = 1.2, 7.8 Hz, 1 H), 6.83 (d,

J = 1.2, 7.8 Hz, 1 H), 5.80 (m, 2 H), 4.72 (dd, J = 2.4, 10.2 Hz, 1 H),

4.16 (m, 1 H), 3.80 (s, 3 H), 2.35 (m, 1 H), 1.98 (m, 1 H), 0.10 (s,

9 H); ¹³C NMR (151 MHz, CDCl₃) δ 155.6, 132.7, 127.7, 127.6,

126.1, 121.7, 120.8, 109.9, 71.4, 70.0, 55.3, 32.9, −3.9; IR (ﬁlm) 1493,

1248, 1049, 841 cm⁻¹; HRMS (EI) m/z 262.1382 [(M⁺), calcd for

C₁₅H₂₂O₂Si, 262.1389].

1

(30%) of 2e as colorless oils. Spectroscopic data for 1e: H NMR

(500 MHz, CDCl₃) δ 7.41 (m, 1 H), 7.19 (m, 3 H), 5.90 (m, 1 H),

5.82 (dq, J = 2.0, 10.0 Hz, 1 H), 4.99 (t, J = 5.0 Hz, 1 H), 3.82

(quintet, J = 3.0 Hz, 1 H), 2.54−2.46 (m, 1 H), 2.42 (s, 3 H), 2.40−

2.34 (m, 2 H), 0.11 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 139.4,

136.3, 130.3, 128.2, 127.2, 126.6, 125.5, 120.4, 69.7 (d, J = 5.8 Hz),

68.5 (d, J = 3.2 Hz), 29.5, 19.4 (d, J = 1.4 Hz,), −3.3; IR (ﬁlm) 3028,

2955, 1247, 1052, 840 cm⁻¹; HRMS (EI) m/z 246.1444 [(M⁺), calcd

1

for C₁₅H₂₂OSi, 246.1440]. Spectroscopic data for 2e: H NMR (500

MHz, CDCl₃) δ 7.45 (d, J = 7.5 Hz, 1 H), 7.23 (t, J = 7.5 Hz, 1 H),

7.17 (dt, J = 1.5, 7.5 Hz, 1 H), 7.13 (d, J = 7.0 Hz, 1 H), 5.84 (m, 2 H),

4.56 (dd, J = 4.5, 8.5 Hz, 1 H), 4.20 (m, 1 H), 2.35 (s, 3 H), 2.22 (m,

2 H), 0.12 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 141.8, 134.6,

130.0, 128.0, 126.8, 126.1, 125.6, 121.5, 73.1 (d, J = 3.9 Hz, 1 H), 71.8,

32.4, 19.2, −3.9; IR (ﬁlm) 3027, 2957, 1247, 1072, 843 cm⁻¹; HRMS

(EI) m/z 246.1436 [(M⁺), calcd for C₁₅H₂₂OSi, 246.1440].

trans-(6-(3-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1c). Applying general procedure F to syn-S3-c

(95.9 mg, 0.33 mmol, 1 equiv) and second-generation Grubbs catalyst

(9.8 mg, 0.012 mmol, 0.035 equiv) in CH₂Cl₂(3.5 mL) for 3 h

aﬀorded after column chromatography (35% CH₂Cl₂in hexanes)

74 mg (86%) of 1c as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ

7.23 (m, 1 H), 6.94 (m, 2 H), 6.79 (m, 1 H), 5.79 (m, 2 H), 4.69 (t,

J = 5.5 Hz, 1 H), 4.03 (m, 1 H), 3.79 (s, 3 H), 2.39 (m, 2 H), 0.09 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 159.6, 143.9, 129.2, 128.1,

120.0, 118.9, 112.6, 112.3, 72.3, 70.2, 55.2, 30.3, −2.9; IR (ﬁlm) 1248,

1051, 841 cm⁻¹; HRMS (EI) m/z 262.1400 [(M⁺), calcd for

C₁₅H₂₂O₂Si, 262.1389].

trans-Trimethyl(6-(3-methylphenyl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1f) and cis-Trimethyl(6-(3-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (2f). Applying general procedure F to syn/anti-S3-f

(∼2:1 ratio, 228 mg, 0.8307 mmol, 1 equiv) and second-generation

Grubbs catalyst (24.8 mg, 0.029 mmol, 0.035 equiv) in CH₂Cl₂

(9 mL) for 3 h aﬀorded after column chromatography (15%

CH₂Cl₂in hexanes and 5% EtOAc in hexanes) 120 mg (59%) of 1f

and 60 mg (29%) of 2f as colorless oils. Spectroscopic data for 1f: ¹H

NMR (600 MHz, CDCl₃) δ 7.23 (t, J = 7.8 Hz, 1 H), 7.19 (m, 2 H),

7.09 (d, J = 7.8 Hz, 1 H), 5.81 (m, 2 H), 4.69 (t, J = 6.0 Hz, 1 H), 4.07

(m, 1 H), 2.39 (m, 2 H), 2.36 (s, 3 H), 0.12 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 142.2, 137.8, 128.09, 128.06, 128.0, 127.2, 123.6,

120.1, 72.5, 70.4, 30.5, 21.5, −2.9; IR (ﬁlm) 3028, 2917, 1247, 1055,

840 cm⁻¹; HRMS (EI) m/z 246.1440 [(M⁺), calcd for C₁₅H₂₂OSi,

cis-(6-(3-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (2c). Applying general procedure F to anti-S3-c

(109 mg, 0.375 mmol, 1 equiv) and second-generation Grubbs cata-

lyst (17.7 mg, 0.021 mmol, 0.04 equiv) in CH₂Cl₂(5.5 mL) for 3 h

aﬀorded after column chromatography (30% CH₂Cl₂in hexanes) 91

mg (92%) of 2c as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.23

(t, J = 8.0 Hz, 1 H), 6.92 (m, 2 H), 6.78 (ddd, J = 0.5, 2.5, 8.0 Hz,

1 H), 5.79 (m, 2 H), 4.37 (dd, J = 3.0, 10.0 Hz, 1 H), 4.15 (m, 1 H),

3.79 (s, 3 H), 2.23 (m, 1 H), 2.15 (m, 1 H), 0.08 (s, 9 H); ¹³C NMR

(126 MHz, CDCl₃) δ 159.5, 145.8, 129.1, 128.0, 121.1, 118.0, 112.2,

111.4, 75.2, 71.6, 55.1, 34.1, −4.0; IR (ﬁlm) 1248, 1049, 841 cm⁻¹;

HRMS (EI) m/z 262.1394 [(M⁺), calcd for C₁₅H₂₂O₂Si, 262.1389].

trans-(6-(4-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1d). Applying general procedure F to syn-S3-d

(155 mg, 0.534 mmol, 1 equiv) and second-generation Grubbs catalyst

(14 mg, 0.016 mmol, 0.03 equiv) in CH₂Cl₂(6 mL) for 3 h aﬀorded

after column chromatography (35% CH₂Cl₂in hexanes) 126 mg

1

246.1440]. Spectroscopic data for 2f: H NMR (600 MHz, CDCl₃) δ

7.24 (t, J = 7.8 Hz, 1 H), 7.18 (m, 2 H), 7.06 (d, J = 7.8 Hz, 1 H), 5.83

(m, 2 H), 4.38 (dd, J = 3.0, 9.6 Hz, 1 H), 4.19 (m, 1 H), 2.37 (s, 3 H),

2.27−2.17 (m, 2 H), 0.12 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ

144.0, 128.1 (2 C), 127.7, 126.4, 122.7, 121.2, 75.5, 71.6, 34.1, 21.5,

−3.9; IR (ﬁlm) 3028, 2917, 1247, 1074, 873 cm⁻¹; HRMS (EI) m/z

246.1436 [(M⁺), calcd for C₁₅H₂₂OSi, 246.1440].

trans-Trimethyl(6-(4-methylphenyl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1g) and cis-Trimethyl(6-(4-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (2g). Applying general procedure F to syn/anti-S3-g

(∼1.15:1 ratio, 228.8 mg, 0.834 mmol, 1 equiv) and second-generation

Grubbs catalyst (28.3 mg, 0.033 mmol, 0.04 equiv) in CH₂Cl₂(9 mL)

for 3 h aﬀorded after column chromatography (10% CH₂Cl₂in

hexanes and 6% EtOAc in hexanes) 108 mg (53%) of 1g and 88 mg

1

(43%) of 2g as colorless oils. Spectroscopic data for 1g: H NMR

1

(90%) of 1d as a colorless oil: H NMR (500 MHz, CDCl₃) δ 7.30

(500 MHz, CDCl₃) δ 7.26 (d, J = 7.5 Hz, 2 H), 7.14 (d, J = 8 Hz,

2 H), 5.83−5.76 (m, 2 H), 4.71 (t, J = 5.5 Hz, 1 H), 4.00 (m, 1 H),

2.39 (m, 2 H), 2.33 (s, 3 H), 0.09 (s, 9 H); ¹³C NMR (126 MHz,

(d, J = 9.0 Hz, 2 H), 6.87 (d, J = 9.0 Hz, 1 H), 5.80 (m, 2 H), 4.70

(t, J = 5.0 Hz, 1 H), 3.98 (m, 1 H), 3.79 (s, 3 H), 2.40 (m, 2 H), 0.10

Q

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

CDCl₃) δ 139.1, 136.8, 128.9 (2 C), 128.1, 126.6 (2 C), 120.1, 72.2,

69.8, 30.1, 21.1, −2.9; IR (ﬁlm) 3028, 2955, 1248, 1053, 841 cm⁻¹;

HRMS (EI) m/z 246.1452 [(M⁺), calcd for C₁₅H₂₂OSi, 246.1440].

Spectroscopic data for 2g: ¹H NMR (500 MHz, CDCl₃) δ 7.23 (d, J =

8.0 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H), 5.82−5.77 (m, 2 H), 4.36 (dd,

J = 4.0, 9.5 Hz, 1 H), 4.15 (m, 1 H), 2.33 (s, 3 H), 2.24−2.13 (m,

2 H), 0.08 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 141.1, 136.5,

128.8 (2 C), 128.1, 125.6 (2 C), 121.2, 75.3, 71.6, 34.1, 21.1, −4.0; IR

(ﬁlm) 3028, 2957, 1248, 1072, 858, 841 cm⁻¹; HRMS (EI) m/z

246.1440 [(M⁺), calcd for C₁₅H₂₂OSi, 246.1440].

300.1151 [(M⁺), calcd for C₁₅H₁₉OSiF₃, 300.1157]. Spectroscopic

data for 2j: ¹H NMR (500 MHz, CDCl₃) δ 7.59 (d, J = 8.0 Hz, 2 H),

7.47 (d, J = 8.0 Hz, 1 H), 5.87−5.79 (m, 2 H), 4.46 (dd, J = 3.0,

10.0 Hz, 1 H), 4.19 (m, 1 H), 2.27 (m, 1 H), 2.14 (m, 1 H), 0.12 (s,

9 H); ¹³C NMR (151 MHz, CDCl₃) δ 147.9, 129.2 (q, J = 38.4 Hz),

128.1, 125.9 (2 C), 125.1 (q, J = 4.7 Hz, 2 C), 124.3 (q, J = 324.3 Hz),

120.7, 74.9, 71.7, 34.0, −4.1; IR (neat) 1325, 1250, 1165, 1126, 1068,

841 cm⁻¹; HRMS (EI) m/z 300.1157 [(M⁺), calcd for C₁₅H₁₉OSiF₃,

300.1157].

trans-(6-([1,1′-Biphenyl]-4-yl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1k) cis-(6-([1,1′-Biphenyl]-4-yl)-5,6-dihydro-2H-

pyran-2-yl)trimethylsilane and (2k). Applying general procedure F

to syn/anti-S3-k (∼2:1 ratio, 161 mg, 0.478 mmol, 1 equiv) and second-

generation Grubbs catalyst (16.2 mg, 0.0191 mmol, 0.04 equiv) in

CH₂Cl₂(5 mL) for 3 h aﬀorded after column chromatography (15%

and 35% CH₂Cl₂in hexanes) 24.6 mg (17%) of 1k and 67 mg (46%) of

trans-(6-(4-Fluorophenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1h). Applying general procedure F to syn-S3-h

(95 mg, 0.341 mmol, 1 equiv) and second-generation Grubbs catalyst

(11.6 mg, 0.014 mmol, 0.04 equiv) in CH₂Cl₂(4 mL) for 3 h aﬀorded

after column chromatography (30% CH₂Cl₂in hexanes) 75.2 mg

1

(88%) of 1h as a colorless oil: H NMR (500 MHz, CDCl₃) δ 7.34

1

(dd, J = 5.5, 9.0 Hz, 2 H), 7.01 (t, J = 9.0 Hz, 2 H), 5.79 (m, 2 H), 4.70

(t, J = 5.5 Hz, 1 H), 3.98 (m, 1 H), 2.44−2.32 (m, 2 H), 0.09 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 162.0 (d, J = 247.1 Hz), 137.7 (d, J =

3.0 Hz), 128.3 (d, J = 8.0 Hz, 2 C), 128.2, 119.8, 114.9 (d, J = 21.2 Hz,

2 C), 71.6, 69.8, 30.1, −3.0; IR (ﬁlm) 3030, 2957, 2899, 1510, 1248,

1055, 841 cm⁻¹; HRMS (EI) m/z 250.1177 [(M⁺), calcd for

C₁₄H₁₉OSiF, 250.1189].

cis-(6-(4-Fluorophenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (2h). Applying general procedure G to anti-S3-h (93

mg, 0.334 mmol, 1 equiv) and second-generation Grubbs catalyst

(11.3 mg, 0.013 mmol, 0.04 equiv) in benzene (4.2 mL) for 1 h at

80 °C aﬀorded after column chromatography (10% CH₂Cl₂in

hexanes) 77.5 mg (93%) of 2h as a colorless oil: ¹H NMR (500 MHz,

CDCl₃) δ 7.30 (m, 2 H), 7.00 (m, 2 H), 5.80 (m, 2 H), 4.37 (dd, J =

3.5,10.0 Hz, 1 H), 4.17 (m, 1 H), 2.21 (m, 1 H), 2.13 (m, 1 H), 0.09

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 161.9 (d, J = 244.9 Hz),

139.8 (d, J = 3.5 Hz), 128.1, 127.2 (d, J = 7.9 Hz, 2 C), 121.0, 114.9

(d, J = 21.2 Hz, 2 C), 74.8, 71.7, 34.2, −4.0; IR (ﬁlm) 3030, 2959,

2775, 1512, 1248, 839 cm⁻¹; HRMS (EI) m/z 250.1183 [(M⁺), calcd

for C₁₄H₁₉OSiF, 250.1189].

2k as colorless oils. Spectroscopic data for 1k: H NMR (500 MHz,

CDCl₃) δ 7.58 (m, 4 H), 7.44 (m, 4 H), 7.33 (m, 1 H), 5.83 (m, 2 H),

4.79 (t, J = 6.0 Hz, 1 H), 4.06 (m, 1 H), 2.45 (m, 2 H), 0.12 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 141.2, 141.0, 140.1, 128.7 (2 C), 128.2,

127.1, 127.08 (2 C), 127.05 (2 C), 126.97 (2 C), 120.0, 72.1, 70.0, 30.2,

−2.9; IR (ﬁlm) 3028, 2955, 1248, 1070, 841 cm⁻¹; HRMS (EI) m/z

308.1584 [(M⁺), calcd for C₂₀H₂₄OSi, 308.1596]. Spectroscopic data for

2k: ¹H NMR (500 MHz, CDCl₃) δ 7.59 (m, 4 H), 7.44 (m, 4 H), 7.43

(m, 1 H), 5.85 (m, 2 H), 4.47 (dd, J = 3.5, 10.0 Hz, 1 H), 4.22 (s, 1 H),

2.33−2.20 (m, 2 H), 0.12 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

143.1, 141.1, 139.9, 128.7 (2 C), 128.1, 127.1 (3 C), 126.9 (2 C), 126.1

(2 C), 121.1, 75.2, 71.7, 34.1, −4.0; IR (ﬁlm) 3030, 2957, 1246, 1070,

841 cm⁻¹; HRMS (EI) m/z 308.1594 [(M⁺), calcd for C₂₀H₂₄OSi,

308.1596].

trans-Trimethyl(6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1l). Applying general procedure G to syn-S3-l (102 mg,

0.328 mmol, 1 equiv) and second-generation Grubbs catalyst

(11.2 mg, 0.013 mmol, 0.04 equiv) in benzene (4.1 mL) for 1 h at

80 °C aﬀorded after column chromatography (40% CH₂Cl₂in

hexanes) 83.4 mg (90%) of 1l as a colorless oil: ¹H NMR (600 MHz,

CDCl₃) δ 7.81 (m, 4 H), 7.54 (dd, J = 1.8, 8.4 Hz, 1 H), 7.45 (m,

2 H), 5.87 (m, 1 H), 5.81 (m, 1 H), 4.91 (t, J = 6.0 Hz, 1 H), 4.04

(quintet, J = 3.0 Hz, 1 H), 2.52 (m, 2 H), 0.12 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 139.5, 133.2, 132.8, 128.2, 128.0, 127.9, 127.6,

125.9, 125.7, 125.2, 125.1, 120.0, 72.5, 69.9, 30.2, −3.0; IR (ﬁlm) 3028,

2955, 2897, 1248, 841 cm⁻¹; HRMS (EI) m/z 282.1436 [(M⁺), calcd

for C₁₈H₂₂OSi, 282.1440].

trans-(6-(4-Chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (1i) and cis-(6-(4-Chlorophenyl)-5,6-dihydro-2H-

pyran-2-yl)trimethylsilane (2i). Applying general procedure F to

syn/anti-S3-i (∼1:1.4 ratio, 210 mg, 0.746 mmol, 1 equiv) and second-

generation Grubbs catalyst (25.3 mg, 0.03 mmol, 0.04 equiv) in CH₂Cl₂

(8 mL) for 3 h aﬀorded after column chromatography (10% and 25%

CH₂Cl₂in hexanes) 75.5 mg (38%) of 1i and 105.6 mg (53%) of 2i as

colorless oils. Spectroscopic data for 1i: ¹H NMR (500 MHz, CDCl₃) δ

7.30 (m, 4 H), 5.78 (m, 2 H), 4.71 (dd, J = 5.0, 10.0 Hz, 1 H), 3.97 (m,

1 H), 2.42 (m, 1 H), 2.34 (m, 1 H), 0.09 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 140.6, 132.9, 128.3 (2 C), 128.2, 128.0 (2 C), 119.7, 71.6,

69.7, 30.0, −3.0; IR (ﬁlm) 3030, 2956, 1492, 1248, 1090, 1055, 1015,

841 cm⁻¹; HRMS (EI) m/z 266.0890 [(M⁺), calcd for C₁₄H₁₉OSiCl,

cis-Trimethyl(6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)-

silane (2l). Applying general procedure G to anti-S3-l (110 mg,

0.3543 mmol, 1 equiv) and second-generation Grubbs catalyst (12 mg,

0.014 mmol, 0.04 equiv) in benzene (4.4 mL) for 1 h at 80 °C

aﬀorded after column chromatography (10% CH₂Cl₂in hexanes)

1

93 mg (93%) of 2l as a colorless oil: H NMR (500 MHz, CDCl₃) δ

266.0894]. Spectroscopic data for 2i: H NMR (500 MHz, CDCl₃) δ

7.81 (m, 4 H), 7.48 (dd, J = 1.5, 8.5 Hz, 1 H), 7.44 (m, 2 H), 5.84 (m,

2 H), 4.56 (dd, J = 3.5, 9.5 Hz, 1 H), 4.23 (m, 1 H), 2.34−2.22 (m,

2 H), 0.12 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 141.4, 133.3,

132.8, 128.1, 127.9, 127.8, 127.6, 125.8, 125.5, 124.3, 124.1, 121.1,

75.5, 71.7, 34.0, −4.0; IR (ﬁlm) 3028, 2957, 2772, 1246, 1072,

841 cm⁻¹; HRMS (EI) m/z 267.1217 [(M − CH₃)⁺, calcd for

C₁₇H₁₉OSi, 267.1205].

trans-Dimethylphenyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane

(1m). Applying general procedure F to syn/anti-S3-m (∼13:1 ratio,

99 mg, 0.307 mmol, 1 equiv) and second-generation Grubbs catalyst

(10 mg, 0.0123 mmol, 0.04 equiv) in CH₂Cl₂(3.5 mL) at room

temperature aﬀorded after column chromatography (10% and 30%

CH₂Cl₂in hexanes) 80.4 mg (89%) of 1m and 2.5 mg (3%) of 2m as

colorless oils. Spectroscopic data for 1m: ¹H NMR (500 MHz,

CDCl₃) δ 7.58 (m, 2 H), 7.39−7.32 (m, 7 H), 7.26 (m, 1 H), 5.84−

5.77 (m, 2 H), 4.65 (dd, J = 5.0, 6.5 Hz, 1 H), 4.29 (m, 1 H), 2.42−

2.31 (m, 2 H) 0.43 (s, 3 H), 0.40 (s, 3 H); ¹³C NMR (126 MHz,

CDCl₃) δ 142.0, 136.9, 134.1, 129.3, 128.2, 127.8, 127.2, 126.6, 120.5,

72.3, 69.8, 30.2, −4.4, −4.6; IR (ﬁlm) 3071, 2960, 1113, 724 cm⁻¹;

HRMS (EI) m/z 294.1436 [(M⁺), calcd for C₁₉H₂₂OSi, 294.1440].

7.29 (m, 4 H), 5.81 (m, 2 H), 4.37 (dd, J = 3.5, 10.0 Hz, 1 H), 4.17 (m,

1 H), 2.22 (m, 1 H), 2.12 (m, 1 H), 0.10 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 142.5, 132.6, 128.2 (2 C), 128.1, 127.0 (2 C), 120.9, 74.7,

71.7, 34.0, −4.0; IR (ﬁlm) 3030, 2957, 2896, 1490, 1248, 1088, 1073,

1014, 841 cm⁻¹; HRMS (EI) m/z 266.0883 [(M⁺), calcd for

C₁₄H₁₉OSiCl, 266.0894].

trans-Trimethyl(6-(4-(triﬂuoromethyl)phenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (1j) and cis-Trimethyl(6-(4-(triﬂuoromethyl)-

phenyl)-5,6-dihydro-2H-pyran-2-yl)silane (2j). Applying general

procedure F to syn/anti-S3-j (∼1:4.1 ratio, 296 mg, 0.904 mmol,

1 equiv) and second-generation Grubbs catalyst (31 mg, 0.036 mmol,

0.04 equiv) in CH₂Cl₂(9.5 mL) for 3 h aﬀorded after column

chromatography (10% and 25% CH₂Cl₂in hexanes) 50 mg (18%) of

1j and 201 mg (74%) of 2j as colorless oils. Spectroscopic data for 1j:

¹H NMR (500 MHz, CDCl₃) δ 7.58 (d, J = 8.0 Hz, 2 H), 7.48 (d, J =

8.0 Hz, 2 H), 5.80 (m, 2 H), 4.77 (t, J = 5.0 Hz, 1 H), 4.01 (m, 1 H),

2.46 (m, 1 H), 2.36 (m, 1 H), 0.09 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 146.2, 129.4 (q, J = 32.1 Hz), 128.3, 126.8 (2 C), 125.1 (q,

J = 3.9 Hz, 2 C), 124.3 (q, J = 270.8 Hz), 119.6, 71.7, 70.0, 30.1, −3.1;

IR (neat) 1325, 1250, 1126, 1068, 839 cm⁻¹; HRMS (EI) m/z

R

DOI: 10.1021/jo5026942

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The Journal of Organic Chemistry

Article

cis-Dimethylphenyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane

(2m). Applying general procedure F to anti-S3-m (119.8 mg,

0.3714 mmol, 1 equiv) and second-generation Grubbs catalyst

(12.6 mg, 0.0148 mmol, 0.04 equiv) in CH₂Cl₂(4 mL) at room tem-

perature aﬀorded after column chromatography (20% CH₂Cl₂in

2954, 1492, 1244, 814 cm⁻¹; HRMS (EI) m/z 324.1536 [(M⁺), calcd

for C₂₀H₂₄O₂Si, 324.1546].

cis-(6-(3-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

dimethylphenylsilane (2p). Applying general procedure G to anti-S3-p

(95 mg, 0.269 mmol, 1 equiv) and second-generation Grubbs cata-

lyst (9.2 mg, 0.011 mmol, 0.04 equiv) in benzene (3.8 mL) at

80 °C for 1 h aﬀorded after column chromatography (30% CH₂Cl₂in

hexanes) 75.4 mg (87%) of 2p as a colorless oil: ¹H NMR (600 MHz,

CDCl₃) δ 7.63 (m, 2 H), 7.37 (m, 3 H), 7.26 (t, J = 7.8 Hz, 1 H), 6.96

(m, 1 H), 6.94 (dd, J = 0.6, 7.2 Hz, 1 H), 6.81 (ddd, J = 1.2, 3.0,

8.4 Hz, 1 H), 5.79 (m, 2 H), 4.42 (m, 2 H), 3.82 (s, 3 H), 2.25 (m,

1 H), 2.16 (m, 1 H), 0.41 (s, 3 H), 0.39 (s, 3 H); ¹³C NMR

(151 MHz, CDCl₃) δ 159.5, 145.6, 136.7, 134.2 (2 C), 129.2, 129.1,

127.7, 127.6 (2 C), 121.5, 118.0, 112.4, 111.2, 75.3, 71.3, 55.1, 33.9,

−5.2, −5.9; IR (ﬁlm) 3070, 2959, 1494, 1249, 815 cm⁻¹; HRMS (EI)

m/z 324.1546 [(M⁺), calcd for C₂₀H₂₄O₂Si, 324.1546].

trans-(6-(4-Chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)-

dimethylphenylsilane (1q). Applying general procedure G to syn-S3-q

(128 mg, 0.359 mmol, 1 equiv) and second-generation Grubbs catalyst

(12.2 mg, 0.014 mmol, 0.04 equiv) in benzene (5.1 mL) at 80 °C for 1

h aﬀorded after column chromatography (25% CH₂Cl₂in hexanes)

109 mg (92%) of 1q as a colorless oil: ¹H NMR (600 MHz, CDCl₃) δ

7.54 (m, 2 H), 7.39−7.33 (m, 3 H), 7.27 (m, 2 H), 7.21 (m, 2 H),

5.80−5.75 (m, 2 H), 4.58 (t, J = 5.4 Hz, 1 H), 4.22 (m, 1 H), 2.35−

2.27 (m, 2 H), 0.39 (s, 3 H), 0.37 (s, 3 H); ¹³C NMR (151 MHz,

CDCl₃) δ 140.5, 136.7, 134.1 (2 C), 132.9, 129.3, 128.3 (2 C), 128.0

(2 C), 127.9, 127.8 (2 C), 120.3, 71.5, 69.6, 30.0, −4.4, −4.7; IR (ﬁlm)

3068, 2957, 1490, 1249, 809 cm⁻¹; HRMS (EI) m/z 328.1035 [(M⁺),

calcd for C₁₉H₂₁OSiCl, 328.1050].

trans-(6-(4-Chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)-

triethylsilane (1r). Applying general procedure G to syn-S3-r

(94.6 mg, 0.281 mmol, 1 equiv) and second-generation Grubbs cata-

lyst (9.5 mg, 0.012 mmol, 0.04 equiv) in benzene (4 mL) at 80 °C for

1 h aﬀorded after column chromatography (25% CH₂Cl₂in hexanes)

71.9 mg (83%) of 1r as a colorless oil: ¹H NMR (600 MHz, CDCl₃) δ

7.29 (m, 4 H), 5.75 (m, 2 H), 4.71 (t, J = 5.4 Hz, 1 H), 4.09 (m, 1 H),

2.44 (m, 1 H), 2.32 (m, 1 H), 0.96 (t, J = 7.8 Hz, 9 H), 0.62 (q, J =

7.8 Hz, 6 H); ¹³C NMR (151 MHz, CDCl₃) δ 140.5, 132.8, 129.0,

128.3 (2 C), 128.0 (2 C), 119.1, 71.6, 67.4, 29.8, 7.4, 2.5; IR (ﬁlm)

3030, 2953, 2878, 1493, 1014, 819, 715 cm⁻¹; HRMS (EI) m/z

308.1349 [(M⁺), calcd for C₁₇H₂₅OSiCl, 308.1363].

trans-Triethyl(6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1s). Applying general procedure G to syn-S3-s (99.5 mg,

0.282 mmol, 1 equiv) and second-generation Grubbs catalyst (9.6 mg,

0.0113 mmol, 0.04 equiv) in benzene (4 mL) at 80 °C for 1 h aﬀorded

after column chromatography (25% CH₂Cl₂in hexanes) 85.7 mg

(94%) of 1s as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.85 (m,

4 H), 7.57 (dd, J = 1.5, 8.5 Hz, 1 H), 7.49 (m, 2 H), 5.85 (m, 2 H),

4.96 (t, J = 5.0 Hz, 1 H), 4.20 (m, 1 H), 2.63−2.52 (m, 2 H), 1.03 (t,

J = 8.0 Hz, 9 H), 0.70 (dq, J = 1.5, 8.0 Hz, 6 H); ¹³C NMR (126 MHz,

CDCl₃) δ 139.4, 133.2, 132.7, 129.0, 128.1, 127.8, 127.6, 125.8, 125.6,

125.3, 125.1, 119.4, 72.4, 67.6, 29.9, 7.5, 2.6; IR (ﬁlm) 3055, 2953,

2874, 1458, 1018, 817, 719 cm⁻¹; HRMS (EI) m/z 324.1902 [(M⁺),

calcd for C₂₁H₂₈OSi, 324.1909].

1

hexanes) 99 mg (91%) of 2m as a colorless oil: H NMR (500 MHz,

CDCl₃) δ 7.68 (m, 2 H), 7.43−7.38 (m, 7 H), 7.31 (t, J = 7 Hz, 1 H),

5.84 (m, 2 H), 4.48 (m, 2 H), 2.33−2.19 (m, 2 H), 0.47 (s, 3 H), 0.45

(s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.9, 136.7, 134.2, 129.2,

128.1, 127.8, 127.7, 127.0, 125.6, 121.5, 75.5, 71.3, 34.0, −5.1, −5.9; IR

(ﬁlm) 3071, 2959, 1428, 1115, 724 cm⁻¹; HRMS (EI) m/z 294.1440

[(M⁺), calcd for C₁₉H₂₂OSi, 294.1440].

trans-Methyldiphenyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane

(1n) and cis-Methyldiphenyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)-

silane (2n). Applying general procedure G to syn/anti-S3-n (∼1:1.7

ratio, 312 mg, 0.811 mmol, 1 equiv) and second-generation Grubbs

catalyst (27.5 mg, 0.032 mmol, 0.04 equiv) in benzene (11.6 mL) at

room temperature aﬀorded after column chromatography (20% and

30% CH₂Cl₂in hexanes) 75 mg (26%) of 1n and 101 mg (35%) of 2n

as colorless oils. Spectroscopic data for 1n: ¹H NMR (500 MHz,

CDCl₃) δ 7.63 (m, 2 H), 7.59 (m, 2 H), 7.49−7.23 (m, 11 H), 5.87−

5.80 (m 2 H), 4.63 (m, 2 H), 2.43−2.32 (m, 2 H), 0.66 (s, 3 H); ¹³C

NMR (126 MHz, CDCl₃) δ 141.7, 135.3, 135.13 (2 C), 135.08 (2 C),

134.97, 129.5, 129.4, 128.1 (2 C), 127.9 (2 C), 127.8 (2 C), 127.7,

127.2, 126.7 (2 C), 121.1, 72.1, 68.5, 29.7, −5.5; IR (ﬁlm) 3071, 2975,

1111, 724 cm⁻¹; HRMS (EI) m/z 356.1579 [(M⁺), calcd for C₂₄H₂₄OSi,

1

356.1596]. Spectroscopic data for 2n: H NMR (500 MHz, CDCl₃) δ

7.65 (m, 4 H), 7.41−7.30 (m, 10 H), 7.24 (m, 1 H), 5.80 (m, 2 H), 4.76

(m, 1 H), 4.49 (dd, J = 3.0, 10.0 Hz, 1 H), 2.26 (m, 1 H), 2.19 (m, 1 H),

0.64 (s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.8, 135.22 (2 C),

135.16, 135.1 (2 C), 134.8, 129.5, 129.4, 128.1 (2 C), 127.8 (2 C), 127.7

(2 C), 127.6, 126.9, 125.6 (2 C), 122.1, 75.8, 70.9, 33.9, −6.4; IR (ﬁlm)

3069, 2963, 1427, 788, 696 cm⁻¹; HRMS (EI) m/z 356.1587 [(M⁺),

calcd for C₂₄H₂₄OSi, 356.1596].

trans-Triethyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane (1o).

Applying general procedure F to syn-S3-o (73.5 mg, 0.243 mmol,

1 equiv) and second-generation Grubbs catalyst (8.3 mg, 0.01 mmol,

0.04 equiv) in CH₂Cl₂(3 mL) at room temperature aﬀorded after

column chromatography (25% CH₂Cl₂in hexanes) 55.9 mg (84%) of

1

1o as a colorless oil: H NMR (600 MHz, CDCl₃) δ 7.37 (d, J = 7.2

Hz, 2 H), 7.32 (t, J = 7.2 Hz, 2 H), 7.24 (m, 1 H), 5.76 (m, 2 H), 4.74

(t, J = 5.4 Hz, 1 H), 4.14 (m, 1 H), 2.44 (m, 1 H), 2.39 (m, 1 H), 0.97

(t, J = 7.8 Hz, 9 H), 0.64 (q, J = 7.8 Hz, 6 H); ¹³C NMR (126 MHz,

CDCl₃) δ 142.0, 128.9, 128.1 (2 C), 127.1, 126.6 (2 C), 119.4, 72.3,

67.7, 30.0, 7.5, 2.6; IR (ﬁlm) 3030, 2955, 1454, 1072 cm⁻¹; HRMS

(EI) m/z 274.1737 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

cis-Triethyl(6-phenyl-5,6-dihydro-2H-pyran-2-yl)silane (2o). Ap-

plying general procedure G to anti-S3-o (102 mg, 0.337 mmol,

1 equiv) and second-generation Grubbs catalyst (11.4 mg, 0.013 mmol,

0.04 equiv) in benzene (4.8 mL) at 80 °C for 1 h aﬀorded after column

chromatography (10% CH₂Cl₂in hexanes) 88 mg (95%) of 2o as a

1

colorless oil: H NMR (500 MHz, CDCl₃) δ 7.33 (m, 4 H), 7.24 (m,

1 H), 5.84 (m, 1 H), 5.76 (m, 1 H), 4.39 (dd, J = 3.5, 9.5 Hz, 1 H), 4.33

(m, 1 H), 2.28−2.16 (m, 2 H), 1.01 (t, J = 8.0 Hz, 9 H), 0.68 (q, J =

8.0 Hz, 6 H); ¹³C NMR (126 MHz, CDCl₃) δ 144.2, 128.7, 128.1

(2 C), 126.9, 125.6 (2 C), 120.7, 75.7, 70.2, 34.1, 7.5, 1.9; IR (ﬁlm)

3028, 2953, 1454, 1072 cm⁻¹; HRMS (EI) m/z 274.1746 [(M⁺), calcd

for C₁₇H₂₆OSi, 274.1753].

trans-(6-(3-Methoxyphenyl)-5,6-dihydro-2H-pyran-2-yl)-

dimethylphenylsilane (1p). Applying general procedure F to syn-S3-p

(174 mg, 0.4936 mmol, 1 equiv) and second-generation Grubbs

catalyst (17 mg, 0.0197 mmol, 0.04 equiv) in CH₂Cl₂(5 mL) at room

temperature for 3 h aﬀorded after column chromatography (40%

CH₂Cl₂in hexanes) 137.4 mg (86%) of 1p as a colorless oil: ¹H NMR

(600 MHz, CDCl₃) δ 7.57 (m, 2 H), 7.39−7.34 (m, 3 H), 7.24 (t, J =

8.4 Hz, 1 H), 6.89 (m, 2 H), 6.80 (m, 1 H), 5.83−5.77 (m, 2 H), 4.62

(t, J = 5.4 Hz, 1 H), 4.30 (m, 1 H), 3.79 (s, 3 H), 2.40−2.31 (m, 2 H),

0.42 (s, 3 H), 0.39 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ 159.5,

143.7, 136.9, 134.1 (2 C), 129.3, 129.1, 127.8 (2 C), 127.7, 120.5,

118.9, 112.7, 112.2, 72.2, 69.9, 55.1, 30.2, −4.4, −4.6; IR (ﬁlm) 3071,

cis-Triethyl(6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran-2-yl)silane

(2s). Applying general procedure G to anti-S3-s (102.2 mg, 0.29 mmol,

1 equiv) and second-generation Grubbs catalyst (9.8 mg, 0.0116

mmol, 0.04 equiv) in benzene (4.1 mL) at 80 °C for 1 h aﬀorded after

column chromatography (10% CH₂Cl₂in hexanes) 74.8 mg (79%) of

1

2s as a colorless oil: H NMR (500 MHz, CDCl₃) δ 7.81 (m, 4 H),

7.49 (dd, J = 1.0, 8.0 Hz, 1 H), 7.44 (m, 2 H), 5.88 (m, 1 H), 5.81 (m,

1 H), 4.55 (dd, J = 4.5, 9.5 Hz, 1 H), 4.39 (m, 1 H), 2.31 (m, 2 H),

1.04 (t, J = 8.0 Hz, 9 H), 0.70 (dq, J = 1.5, 8.0 Hz, 6 H); ¹³C NMR

(126 MHz, CDCl₃) δ 141.6, 133.3, 132.7, 128.7, 128.0, 127.8, 127.6,

125.8, 125.5, 124.3, 124.1, 120.7, 75.9, 70.3, 34.0, 7.5, 1.9; IR (ﬁlm)

3028, 2951, 2874, 1458, 1072, 815, 715 cm⁻¹; HRMS (EI) m/z

324.1894 [(M⁺), calcd for C₂₁H₂₈OSi, 324.1909].

trans-Trimethyl(6-(2-propylphenyl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1t). Applying general procedure G to syn-S3-t (36 mg,

0.119 mmol, 1 equiv) and second-generation Grubbs catalyst (4 mg,

S

DOI: 10.1021/jo5026942

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The Journal of Organic Chemistry

Article

0.0048 mmol, 0.04 equiv) in benzene (2.4 mL) at 80 °C for 1 h

aﬀorded after column chromatography (25% CH₂Cl₂in hexanes)

27.9 mg (85%) of 1t as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ

7.41 (m, 1 H), 7.17 (m, 3 H), 5.86 (dq, J = 3.5, 10.0 Hz, 1 H), 5.81

(m, 1 H), 4.97 (t, J = 5.5 Hz, 1 H), 3.90 (quintet, J = 3.0 Hz, 1 H),

2.72−2.60 (m, 2 H), 2.42−2.31 (m, 2 H), 1.61 (m, 2 H), 0.98 (t, J =

7.0 Hz, 3 H), 0.07 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 140.6,

139.3, 129.2, 128.1, 127.2, 126.9, 125.6, 120.5, 69.4, 69.1, 34.6, 30.7,

24.9, 14.3, −3.1; IR (ﬁlm) 3028, 2959, 2872, 1248. 839 cm⁻¹; HRMS

(EI) m/z 274.1755 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

cis-Trimethyl(6-(2-propylphenyl)-5,6-dihydro-2H-pyran-2-yl)-

silane (2t). Applying general procedure G to anti-S3-t (57 mg,

0.188 mmol, 1 equiv) and second-generation Grubbs catalyst (6.4 mg,

0.0075 mmol, 0.04 equiv) in benzene (3.8 mL) at 80 °C for 1 h

aﬀorded after column chromatography (12% CH₂Cl₂in hexanes)

38.6 mg (75%) of 2t as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ

7.43 (dd, J = 2.0, 7.0 Hz, 1 H), 7.20 (m, 2 H), 7.15 (m, 1 H), 5.83 (m,

2 H), 4.58 (dd, J = 3.0, 10.0 Hz, 1 H), 4.18 (m, 1 H), 2.62 (m, 2 H),

2.25 (m, 1 H), 2.17 (m, 1 H), 1.63 (m, 2 H), 0.99 (t, J = 7.0 Hz, 3 H),

0.09 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 141.4, 139.3, 128.9,

128.0, 126.9, 126.1, 126.0, 121.6, 72.7, 71.9, 34.5, 33.4, 24.6, 14.3,

−3.9; IR (ﬁlm) 3028, 2959, 2872, 1248, 841 cm⁻¹; HRMS (EI) m/z

274.1740 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

trans-Trimethyl(3-methyl-6-(4-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (1w) and cis-Trimethyl(3-methyl-6-(4-methyl-

phenyl)-5,6-dihydro-2H-pyran-2-yl)silane (2w). Applying general

procedure G to syn/anti-S3-w (∼1.5:1 ratio, 159 mg, 0.551 mmol,

1 equiv) and second-generation Grubbs catalyst (17.6 mg, 0.021 mmol,

0.04 equiv) in benzene (7 mL) at 80 °C for 1 h aﬀorded after column

chromatography (15% and 35% CH₂Cl₂in hexanes) 86 mg (60%) of

1w and 55 mg (38%) of 2w as colorless oils. Spectroscopic data for 1w:

¹H NMR (600 MHz, CDCl₃) δ 7.26 (d, J = 8.4 Hz, 2 H), 7.14 (d, J =

7.8 Hz, 2 H), 5.49 (m, 1 H), 4.52 (dd, J = 4.2, 9.0 Hz, 1 H), 4.02 m,

1 H), 2.34 (s, 3 H), 2.31 (m, 2 H), 1.65 (m, 3 H), 0.16 (s, 9 H); ¹³C

NMR (151 MHz, CDCl₃) δ 139.8, 136.7, 135.3, 128.9 (2 C), 125.9 (2

C), 115.9, 74.9, 72.8, 32.2, 21.1, 20.4, −1.4; IR (ﬁlm) 3026, 2959, 1250,

839 cm⁻¹; HRMS (EI) m/z 260.1583 [(M⁺), calcd for C₁₆H₂₄OSi,

1

260.1596]. Spectroscopic data for 2w: H NMR (600 MHz, CDCl₃) δ

7.25 (d, J = 7.8 Hz, 2 H), 7.14 (d, J = 7.8 Hz, 2 H), 5.52 (m, 1 H), 4,28

(dd, J = 3.0, 4.2 Hz, 1 H), 4.07 (m, 1 H), 2.34 (s, 3 H), 2.21 (m, 1 H),

2.12 (m, 1 H), 1.68 (m, 3 H), 0.15 (s, 9 H); ¹³C NMR (151 MHz,

CDCl₃) δ 141.1, 136.4, 135.3, 128.7 (2 C), 125.6 (2 C), 117.1, 74.8,

74.3, 34.2, 21.1, 20.0, −2.6; IR (ﬁlm) 3028, 2963, 1248, 843 cm⁻¹;

HRMS (EI) m/z 260.1590 [(M⁺), calcd for C₁₆H₂₄OSi, 260.1596].

trans-Trimethyl(6-phenyl-3-(prop-1-en-2-yl)-5,6-dihydro-2H-

pyran-2-yl)silane (1x). Applying general procedure F to syn-S3-x

(201 mg, 0.738 mmol, 1 equiv) and second-generation Grubbs catalyst

(25 mg, 0.03 mmol, 0.04 equiv) in CH₂Cl₂(8 mL) at room tempera-

ture for 12 h aﬀorded after column chromatography (4% EtOAc in

hexanes) 125 mg (62%) of 1x as a colorless oil: ¹H NMR (500 MHz,

CDCl₃) δ 7.37−7.31 (m, 4 H), 7.25 (tt, J = 1.5, 7 Hz, 1 H), 5.83 (m,

1 H), 4.92 (s, 1 H), 4.82 (s, 1 H), 4.65 (q, J = 2.0 Hz, 1 H), 4.56 (dd,

J = 6.0, 8.5 Hz, 1 H), 2.42 (m, 2 H), 1.89 (t, J = 0.5, Hz, 3 H), 0.10 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 142.8, 141.5, 140.5, 128.3

(2 C), 127.3, 125.8 (2 C), 117.8, 112.3, 72.8, 71.8, 32.7, 21.4, −0.8; IR

(neat) 3089, 3031, 2955, 2895, 1450, 1248, 1028, 839 cm⁻¹; HRMS

(EI) m/z 272.1590 [(M⁺), calcd for C₁₇H₂₄OSi, 272.1596].

trans-Trimethyl(3-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-yl)-

silane (1u) and cis-Trimethyl(3-methyl-6-phenyl-5,6-dihydro-2H-

pyran-2-yl)silane (2u). Applying general procedure F to syn/anti-S3-u

(∼1:1 ratio, 309 mg, 1.126 mmol, 1 equiv) and second-generation

Grubbs catalyst (38 mg, 0.045 mmol, 0.04 equiv) in CH₂Cl₂(13 mL)

at room temperature for 3 h aﬀorded after column chromatography

(10% and 25% CH₂Cl₂in hexanes) 159 mg (57%) of 1u and 100 mg

1

of 2u (36%) as colorless oils. Spectroscopic data for 1u: H NMR

(500 MHz, CDCl₃) δ 7.36−7.30 (m, 4 H), 7.24 (tt, J = 1.5, 6.5 Hz,

1 H), 5.47 (m, 1 H), 4.54 (dd, J = 5.0, 7.5 Hz, 1 H), 4.01 (d, J =

1.0 Hz, 1 H), 2.33−2.29 (m, 2, H), 1.68 (m, 3 H), 0.18 (s, 9 H); ¹³C

NMR (126 MHz, CDCl₃) δ 142.8, 135.4, 128.2 (2 C), 127.1, 126.0

(2 C), 115.8, 75.0, 72.9, 32.1, 20.4, −1.4; IR (ﬁlm) 3029, 2957, 1250,

839 cm⁻¹; HRMS (EI) m/z 246.1440 [(M⁺), calcd for C₁₅H₂₂OSi,

246.1440]. Spectroscopic data for 2u: ¹H NMR (500 MHz, CDCl₃) δ

7.32 (m, 4 H), 7.22 (m, 1 H), 5.51 (m, 1 H), 4.29 (dd, J = 3.0, 8.5 Hz,

1 H), 4.05 (m, 1 H), 2.20 (m, 1 H), 2.10 (m, 1 H), 1.66 (m, 3 H), 0.13

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 144.0, 135.3, 128.1 (2 C),

126.8, 125.6 (2 C), 117.0, 75.0, 74.4, 34.2, 20.0, −2.6; IR (ﬁlm) 3030,

2957, 1248, 839 cm⁻¹; HRMS (EI) m/z 246.1432 [(M⁺), calcd for

C₁₅H₂₂OSi, 246.1440].

trans-(6-(4-Methoxyphenyl)-3-methyl-5,6-dihydro-2H-pyran-2-

yl)trimethylsilane (1v). Applying general procedure F to syn-S3-v

(94.6 mg, 0.311 mmol, 1 equiv) and second-generation Grubbs cata-

lyst (10.6 mg, 0.0124 mmol, 0.04 equiv) in CH₂Cl₂(3.5 mL) at room

temperature for 3 h aﬀorded after column chromatography (60%

CH₂Cl₂in hexanes) 61.5 mg (72%) of 1v as a colorless oil: ¹H NMR

(500 MHz, CDCl₃) δ 7.28 (m, 2 H), 6.87 (m, 2 H), 5.47 (m, 1 H),

4.49 (dd, J = 4.5, 9.0 Hz, 1 H), 3.99 (m, 1 H), 3.78 (s, 3 H), 2.37−2.24

(m, 2 H), 1.64 (m, 3 H), 0.15 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃)

δ 158.7, 135.3, 134.9, 127.3 (2 C), 115.9, 113.6 (2 C), 74.9, 72.5, 55.2,

32.0, 20.4, −1.4; IR (ﬁlm) 2959, 1248, 838 cm⁻¹; HRMS (EI) m/z

276.1549 [(M⁺), calcd for C₁₆H₂₄O₂Si, 276.1546].

cis-Trimethyl(6-phenyl-3-(prop-1-en-2-yl)-5,6-dihydro-2H-pyran-

2-yl)silane (2x). Applying general procedure F to anti-S3-x (291.7 mg,

1.07 mmol, 1 equiv) and second-generation Grubbs catalyst (74.4 mg

added in two portions, 0.0154 mmol, 0.07 equiv) in CH₂Cl₂(11 mL)

at room temperature for 27 h aﬀorded after column chromatography

1

(4% EtOAc in hexanes) 141.8 mg (49%) of 2x as a colorless oil: H

NMR (500 MHz, CDCl₃) δ 7.34 (m, 4 H), 7.24 (tt, J = 1.5, 7.0 Hz,

1 H), 5.88 (dt, J = 1.5, 7.5 Hz, 1 H), 4.85 (s, 2 H), 4.63 (t, J = 2,0 Hz,

1 H), 4.28 (dd, J = 3.0, 10.0 Hz, 1 H), 2.32 (ddt, J = 3.0, 7.0, 17.0 Hz,

1 H), 2.19 (dddd, J = 2.5, 4.0, 12.5, 16.5 Hz, 1 H), 1.90 (s, 3 H), 0.09

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 143.7, 142.7, 140.7, 128.1

(2 C), 127.0, 125.7 (2 C), 118.5, 111.5, 74.3, 71.5, 34.7, 21.7, −2.3; IR

(neat) 3088, 3030, 2953, 2895, 1452, 1246, 1028, 841 cm⁻¹; HRMS

(EI) m/z 272.1586 [(M⁺), calcd for C₁₇H₂₄OSi, 272.1596].

trans-Trimethyl(4-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-yl)-

silane (1y). Applying general procedure G to syn-S3-y (102 mg, 0.3716

mmol, 1 equiv) and second-generation Grubbs catalyst (12.6 mg,

0.015 mmol, 0.04 equiv) in benzene (10 mL) at 80 °C for 1.5 h

aﬀorded after column chromatography (30% CH₂Cl₂in hexanes)

1

58 mg (63%) of 1y as a colorless oil: H NMR (500 MHz, CDCl₃) δ

7.37−7.31 (m, 4 H), 7.26 (tt, J = 2.0, 7.5 Hz, 1 H), 5.47 (m, 1 H), 4.73

(t, J = 5.5 Hz, 1 H), 3.95 (m, 1 H), 2.29 (m, 2 H), 1.78 (m, 3 H), 0.08

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 142.2, 128.2, 127.5, 127.2,

126.6, 121.2, 72.5, 69.5, 34.8, 23.4, −2.9; IR (ﬁlm) 3030, 2959, 1248,

1099, 841 cm⁻¹; HRMS (EI) m/z 246.1433 [(M⁺), calcd for

C₁₅H₂₂OSi, 246.1440].

cis-(6-(4-Methoxyphenyl)-3-methyl-5,6-dihydro-2H-pyran-2-yl)-

trimethylsilane (2v). Applying general procedure F to anti-S3-v (116.9

mg, 0.3839 mmol, 1 equiv) and second-generation Grubbs catalyst (13

mg, 0.0154 mmol, 0.04 equiv) in CH₂Cl₂(4 mL) at room temperature

for 3 h aﬀorded after column chromatography (35% CH₂Cl₂in

cis-Trimethyl(4-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-yl)-

silane (2y). Applying general procedure G to anti-S3-y (104.2 mg,

0.3796 mmol, 1 equiv) and second-generation Grubbs catalyst (13 mg,

0.0152 mmol, 0.04 equiv) in benzene (5.4 mL) at 80 °C for 2 h

aﬀorded after column chromatography (10% CH₂Cl₂in hexanes)

1

hexanes) 91 mg (86%) of 2v as a colorless oil: H NMR (600 MHz,

CDCl₃) δ 7.25 (m, 2 H), 6.85 (m, 2 H), 5.49 (m, 1 H), 4.23 (dd, J =

3.0, 10.8 Hz, 1 H), 4.04 (m, 1 H), 3.78 (s, 3 H), 2.16 (m, 1 H), 2.07

(m, 1 H), 1.65 (d, J = 1.2 Hz, 3 H), 0.11 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 158.6, 136.3, 135.3, 126.8 (2 C), 117.1, 113.5

(2 C), 74.6, 74.4, 55.2, 34.2, 20.0, −2.6; IR (ﬁlm) 2964, 1248, 839

cm⁻¹; HRMS (EI) m/z 276.1551 [(M⁺), calcd for C₁₆H₂₄O₂Si,

276.1546].

1

62 mg (67%) of 2y as a colorless oil: H NMR (500 MHz, CDCl₃) δ

7.34 (t, J = 7.5 Hz, 2 H), 7.31 (t, J = 7.5 Hz, 2 H), 7.23 (tt, J = 1.5,

7.0 Hz, 1 H), 5.47 (d, J = 1.0 Hz, 1 H), 4.38 (dd, J = 3.5, 10.0 Hz,

1 H), 4.08 (m, 1 H), 2.15−2.02 (m, 2 H), 1.73 (s, 3 H), 0.06 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 144.1, 128.8, 128.1, 126.9, 125.6, 121,

T

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

75.7, 71.2, 38.9, 23.2, 3.97; IR (ﬁlm) 3035, 2958, 1248, 1099,

840 cm⁻¹; HRMS (EI) m/z 246.1430 [(M⁺), calcd for C₁₅H₂₂OSi,

246.1440].

2.21 (m, 1 H), 0.04 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 156.0,

141.7, 128.1, 120.6, 110.0, 105.8, 71.7, 69.6, 29.8, −4.1; IR (ﬁlm) 3030,

2959, 2776, 1248, 843 cm⁻¹; HRMS (EI) m/z 222.1080 [(M⁺), calcd

for C₁₂H₁₈O₂Si, 222.1076].

Wittig Rearrangements of Cyclic Ethers 1 and 2. 2-(2-

Phenylcyclopropyl)-1-(trimethylsilyl)ethan-1-one (3a) and 5-Phenyl-

1-(trimethylsilyl)cyclopent-2-en-1-ol (4a). Applying general procedure

H to 2a (67.2 mg, 0.289 mmol, 1 equiv) and sec-butyllithium (1.4 M in

cyclohexane, 0.65 mL, 3 equiv) at −78 °C for 3 h aﬀorded after workup

and column chromatography (5% and 10% EtOAc in hexanes) 40.4 mg

(60%) of 3a (dr > 20:1) and 19.2 mg (29%) of 4a (dr > 20:1) as

colorless oils. Spectroscopic data for 3a: ¹H NMR (300 MHz, CDCl₃) δ

7.06−7.27 (m, 5 H), 2.68 (dd, J = 6.3, 16.8 Hz, 2 H), 1.65 (dt, J = 5.1,

9.3 Hz, 1 H), 1.31 (m, 1 H), 1 (m, 1 H), 0.76 (m, 1 H), 0.2 (s, 9 H);

¹³C NMR (62.8 MHz, CDCl₃) δ 247.2, 142.8, 129.1, 128.2, 125.9,

trans-Trimethyl(4-methyl-6-(4-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (1z). Applying general procedure G to syn-S3-z

(148.7 mg, 0.515 mmol, 1 equiv) and second-generation Grubbs

catalyst (17.5 mg, 0.0206 mmol, 0.04 equiv) in benzene (10.5 mL) at

80 °C for 1.5 h aﬀorded after column chromatography (30% CH₂Cl₂

in hexanes) 110 mg (82%) of 1z as a colorless oil: ¹H NMR

(500 MHz, CDCl₃) δ 7.23 (d, J = 7.5 Hz, 2 H), 7.13 (d, J = 8.0 Hz,

2 H), 5.44 (m, 1 H), 4.69 (t, J = 5.5 Hz, 1 H), 3.92 (quintet, J =

2.5 Hz, 1 H), 2.33 (s, 3 H), 2.27 (m, 2 H), 1.77 (m, 3 H), 0.06 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 139.1, 136.8, 128.9 (2 C),

127.6, 126.6 (2 C), 121.2, 72.4, 69.3, 34.7, 23.5, 21.1, −3.0; IR (ﬁlm)

3025, 2959, 2855, 1248, 841 cm⁻¹; HRMS (EI) m/z 260.1583 [(M⁺),

calcd for C₁₆H₂₄OSi, 260.1596].

125.5, 53.1, 22.7, 16.7, 15.7, −3.1; IR (ﬁlm) 3028, 2959, 1711, 1643,

1604, 1496, 1250, 846 cm⁻¹; HRMS (ESI) m/z 233.1362 [(M + H)⁺,

cis-Trimethyl(4-methyl-6-(4-methylphenyl)-5,6-dihydro-2H-

pyran-2-yl)silane (2z). Applying general procedure G to anti-S3-z

(122 mg, 0.4229 mmol, 1 equiv) and second-generation Grubbs cata-

lyst (14.4 mg, 0.0169 mmol, 0.04 equiv) in benzene (8.5 mL) at 80 °C

for 1.5 h aﬀorded after column chromatography (10% CH₂Cl₂in

1

calcd for C₁₄H₂₁OSi, 233.1362]. Spectroscopic data for 4a: H NMR

(300 MHz, CDCl₃) δ 7.19−7.31 (m, 3 H), 7.38 (m, 2 H), 5.98 (dddd,

J = 1.8, 2.7, 4.8, 5.7 Hz, 1 H), 5.76 (dddd, J = 1.5, 2.1, 3.6, 5.7 Hz, 1 H),

3.43 (dd, J = 8.4, 10.5 Hz, 1 H), 2.57−2.79 (m, 2 H), 1.48 (s, 1 H),

−0.31 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 140.4, 137.3,

130.6, 128.5, 128.17, 126.7, 84.4, 60, 35.4, −3.5; IR (neat) 3441, 3059,

2955, 2928, 2856, 1496, 1452, 1246 cm⁻¹; HRMS (ES) m/z 215.1244

[(M − OH)⁺, calcd for C₁₄H₁₉Si, 215.1256].

1

hexanes) 66 mg (60%) of 2z as a colorless oil: H NMR (600 MHz,

CDCl₃) δ 7.24 (d, J = 7.8 Hz, 2 H), 7.13 (d, J = 7.8 Hz, 2 H), 5.46 (d,

J = 1.8, Hz, 1 H), 4.34 (dd, J = 3.0, 10.2 Hz, 1 H), 4.07 (m, 1 H), 2.33

(s, 3 H), 2.11 (m, 1 H), 2.02 (dt, J = 3.0, 16.8 Hz, 1 H), 1.73 (m, 3 H),

0.06 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ 141.1, 136.5, 128.80,

128.78 (2 C), 125.6 (2 C), 121.0, 75.6, 71.2, 38.9, 23.2, 21.1, −3.9; IR

(ﬁlm) 3019, 2959, 2766, 1246, 1101, 841 cm⁻¹; HRMS (EI) m/z

260.1602 [(M⁺), calcd for C₁₆H₂₄OSi, 260.1596].

2-(2-(2-Methoxyphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-

one (3b) and 5-(2-Methoxyphenyl)-1-(trimethylsilyl)cyclopent-2-en-

1-ol (4b). Applying general procedure H to 2b (76 mg, 0.2896 mmol,

1 equiv) and sec-butyllithium (1.4 M in cyclohexane, 0.62 mL, 3 equiv)

at −78 °C for 3 h aﬀorded after workup and column chromatography

(5% and 10% EtOAc in hexanes) 35.5 mg (47%) of 3b (dr = 18:1) as a

colorless oil and 29.6 mg (39%) of 4b (dr > 20:1) as a white solid.

Spectroscopic data for 3b: ¹H NMR (600 MHz, CDCl₃) δ 6.92 (ddd,

J = 2.4, 7.2, 8.4 Hz, 1 H), 6.66 (m, 2 H), 6.62 (d, J = 8.4 Hz, 1 H), 2.84

(dd, A of ABX system, J = 6.0, 16.8 Hz, 1 H), 2.53 (dd, B of ABX

system, J = 7.2, 16.8 Hz, 1 H), 1.91 (dt, J = 4.8, 8.4 Hz, 1 H), 1.30 (m,

1 H), 0.91 (dt, J = 5.4, 8.4 Hz, 1 H), 0.72 (dt, J = 5.4, 9.0 Hz, 1 H),

0.19 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ 247.6, 158.0, 130.9,

126.4, 125.2, 120.5, 110.1, 55.4, 53.3, 16.7, 15.3, 14.7, −3.2; IR (ﬁlm)

2955, 1645, 1248, 1047, 843 cm⁻¹; HRMS (ESI) 263.1464 [(M + H)⁺,

calcd for C₁₅H₂₃O₂Si, 263.1467]. Spectroscopic and melting point data

trans-Trimethyl(6-(thiophene-2-yl)-5,6-dihydro-2H-pyran-2-yl)-

silane (1aa) and cis-Trimethyl(6-(thiophene-2-yl)-5,6-dihydro-2H-

pyran-2-yl)silane (2aa). Applying general procedure F to syn/anti-S3-

aa (∼2:1 ratio, 95 mg, 0.357 mmol, 1 equiv) and second-generation

Grubbs catalyst (12 mg, 0.0143 mmol, 0.04 equiv) in CH₂Cl₂(4 mL)

at room temperature for 3 h aﬀorded after column chromatography

(10% and 20% CH₂Cl₂in hexanes) 53 mg (62%) of 1aa and 27 mg

1

(31%) of 2aa as colorless oils. Spectroscopic data for 1aa: H NMR

(600 MHz, CDCl₃) δ 7.23 (dd, J = 1.8, 5.4 Hz, 1 H), 6.96 (m, 1 H),

6.95 (dd, J = 3.6, 5.4 Hz, 1 H), 5.77 (m, 2 H), 5.05 (t, J = 4.8 Hz, 1 H),

4.00 (m, 1 H), 2.58 (m, 1 H), 2.42 (m, 1 H), 0.08 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 145.5, 128.3, 126.3, 124.7, 124.5, 119.3, 68.5,

68.1, 30.2, −3.3; IR (neat) 3031, 2957, 1248, 1051, 841 cm⁻¹; HRMS

(EI) m/z 238.0840 [(M⁺), calcd for C₁₂H₁₈OSiS, 238.0848].

Spectroscopic data for 2aa: ¹H NMR (600 MHz, CDCl₃) δ 7.21

(dd, J = 1.8, 5.4 Hz, 1 H), 6.95 (dd, J = 3.6, 4.8 Hz, 1 H), 6.92 (m,

1 H), 5.81−5.74 (m, 2 H), 4.64 (t, J = 6.0 Hz, 1 H), 4.18 (m, 1 H),

2.33 (m, 2 H), 0.07 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ 147.6,

128.1, 126.2, 124.1, 122.4, 120.4, 71.96, 71.94, 33.9, −4.1; IR (neat)

3030, 2957, 1248, 1070, 843 cm⁻¹; HRMS (EI) m/z 238.0824 [(M⁺),

calcd for C₁₂H₁₈OSSi, 238.0848].

1

for 4b: mp 46−47 °C; H NMR (600 MHz, CDCl₃) δ 7.37 (dd, J =

1.8, 7.8 Hz, 1 H), 7.23 (m, 1 H), 6.97 (dt, J = 0.6, 7.8 Hz, 1 H), 6.88

(dd, J = 1.2, 8.4 Hz, 1 H), 5.90 (m, 1 H), 5.74 (m, 1 H), 3.87 (s, 1 H,

OMe), 3.87 (m, 1 H, overlapped with OMe), 3.84 (s, 1 H), 2.83 (m, A

of ABX system, 1 H), 2.54 (dddd, B of ABX system, J = 1.2, 3.0, 8.4,

15.6 Hz, 1 H), −0.31 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ 158.0,

136.9, 129.2, 128.7, 127.9, 127.7, 121.1, 110.6, 84.0, 55.6, 52.7, 35.3,

−3.9; HRMS (ESI) 245.1357 [(M − OH)⁺, calcd for C₁₅H₂₁OSi,

245.1362].

trans-(6-(Furan-2-yl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane

(1bb). Applying general procedure F to syn-S3-bb (45.5 mg,

0.1817 mmol, 1 equiv) and second-generation Grubbs catalyst

(6.1 mg, 0.007 mmol, 0.04 equiv) in CH₂Cl₂(2 mL) at room tempera-

ture for 3 h aﬀorded after column chromatography (30% CH₂Cl₂in

hexanes) 33 mg (82%) of 1bb as a colorless oil: ¹H NMR (500 MHz,

CDCl₃) δ 7.36 (m, 1 H), 6.31 (dd, J = 2.0, 3.0 Hz, 1 H), 6.26 (m,

1 H), 5.76 (m, 2 H), 4.86 (t, J = 5.0 Hz, 1 H), 3.86 (m, 1 H), 2.49−

2.37 (m, 2 H), 0.07 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 154.7,

141.9, 128.1, 119.2, 109.9, 107.1, 68.1, 66.4, 27.7, −3.4; IR (neat)

3030, 2955, 1248, 1057, 1012, 841 cm⁻¹; HRMS (EI) m/z 222.1081

[(M⁺), calcd for C₁₂H₁₈O₂Si, 222.1076].

2-(2-(3-Methoxyphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-

one (3c) and 5-(3-Methoxyphenyl)-1-(trimethylsilyl)cyclopent-2-en-

1-ol (4c). Applying general procedure H to 1c (70.4 mg, 0.268 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.2 mL, 1.2 equiv) at

−78 °C for 10 min aﬀorded after workup and column chromatography

(5% and 10% EtOAc in hexanes) 22.9 mg (33%) of 3c (dr = 17:1) and

31.1 mg (44%) of 4c (dr > 20:1) as colorless oils. Spectroscopic data

for 3c: ¹H NMR (500 MHz, CDCl₃) δ 7.14 (t, J = 8.0 Hz, 1 H), 6.66

(m, 2 H), 6.60 (m, 1 H), 2.74 (dd, A of ABX system, J = 6.5, 17.0 Hz,

1 H), 2.57 (dd, B of ABX system, J = 7.0, 17.0 Hz, 1 H), 1.62 (dt, J =

5.0, 8.5 Hz, 1 H), 1.31 (m, 1 H), 0.97 (dt, J = 5.0, 8.5 Hz, 1 H), 0.74

(dt, J = 5.5, 9.0 Hz, 1 H), 0.19 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃)

δ 247.1, 159.7, 144.6, 129.2, 118.4, 111.7, 110.9, 55.1, 53.1, 22.8, 16.8,

15.8, −3.2; IR (ﬁlm) 2957, 1645, 1250, 1157, 1047, 844 cm⁻¹; HRMS

(ESI) 263.1467 [(M + H)⁺, calcd for C₁₅H₂₃O₂Si, 263.1467].

cis-(6-(Furan-2-yl)-5,6-dihydro-2H-pyran-2-yl)trimethylsilane

(2bb). Applying general procedure G to anti-S3-bb (108 mg,

0.431 mmol, 1 equiv) and second-generation Grubbs catalyst (14.6

mg, 0.017 mmol, 0.04 equiv) in benzene (6 mL) at 80 °C for 1 h

aﬀorded after column chromatography (20% CH₂Cl₂in hexanes) 83

1

Spectroscopic data for 4c: H NMR (500 MHz, CDCl₃) δ 7.20 (t,

J = 7.5 Hz, 1 H), 6.97 (m, 2 H), 6.77 (m, 1 H), 5.96 (m, 1 H), 5.76

(m, 1 H), 3.41 (dd, J = 8.0 10.0 Hz, 1 H), 2.70 (m, 1 H), 2.62 (m,

1 H), 1.24 (s, 1 H), −0.3 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

159.5, 142.1, 137.2, 130.5, 129.1, 120.9, 114.4, 112.0, 84.3, 60.0, 55.2,

1

mg (87%) of 2bb as a colorless oil: H NMR (500 MHz, CDCl₃) δ

7.36 (m, 1 H), 6.32 (dd, J = 2.0, 3.0 Hz, 1 H), 6.23 (m, 1 H), 5.77 (m,

2 H), 4.42 (dd, J = 3.0, 5.5 Hz, 1 H), 4.14 (m, 1 H), 2.43 (m, 1 H),

U

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

35.4, −3.4; IR (ﬁlm) 3452, 3055, 2952, 1246, 839 cm⁻¹; HRMS (ESI)

(86%) of 3g (dr > 20:1) and 4.9 mg (7%) of 4g (dr > 20:1) as

colorless oils. Spectroscopic data for 3g: mixture of tautomers (keto/

enol = 1:0.06); H NMR (500 MHz, CDCl₃) δ 7.04 (d, J = 7.5 Hz,

245.1360 [(M − OH)⁺, calcd for C₁₅H₂₁OSi, 245.1362].

1

2-(2-(4-Methoxyphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-

one (3d). Applying general procedure H to 1d (82 mg, 0.312 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.23 mL, 1.2 equiv) at

−78 °C for 10 min aﬀorded after workup and column chromatography

(5% and EtOAc in hexanes) 53.2 mg (65%) of 3d (dr = 15:1) as a

colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.01 (d, J = 8.5 Hz, 2 H),

6.77 (d, J = 8.5 Hz, 2 H), 2.70 (dd, A of ABX system, J = 6.5, 17.0 Hz,

1 H), 2.60 (dd, B of ABX system, J = 7.0, 17.0 Hz, 1 H), 1.59 (dt, J =

4.5, 9.0 Hz, 1 H), 1.22 (m, 1 H), 0.89 (dt, J = 5.0, 8.5 Hz, 1 H), 0.68

(dt, J = 5.0, 8.5 Hz, 1 H), 0.18 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃)

δ 247.7, 157.7, 134.8, 127.1 (2 C), 113.8 (2 C), 55.3, 53.2, 22.0, 16.1,

15.0, −3.1; IR (ﬁlm) 2958, 1644, 843 cm⁻¹; HRMS (ESI) m/z

263.1466 [(M + H)⁺, calcd for C₁₅H₂₃O₂Si, 263.1467].

2-(2-(2-Methylphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one

(3e) and 5-(2-Methylphenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol

(4e). Applying general procedure H to 1e (109 mg, 0.442 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.33 mL, 1.2 equiv)

in THF (5.5 mL) at −78 °C for 10 min aﬀorded after workup and

column chromatography (5% and 10% EtOAc in hexanes) 86.6 mg

(80%) of 3e (dr > 20:1) and 16.3 mg (15%) of 4e (dr > 20:1) as

colorless oils. Spectroscopic data for 3e: ¹H NMR (600 MHz, CDCl₃)

δ 7.13−7.04 (m, 4 H), 2.84 (dd, A of ABX system, J = 6.0, 16.8 Hz,

1 H), 2.63 (dd, B of ABX system, J = 7.2, 16.8 Hz, 1 H), 2.37 (s, 3 H),

1.64 (dt, J = 5.4, 10.2 Hz, 1 H), 1.34 (m, 1 H), 0.92 (dt, J = 5.4,

9.0 Hz, 1 H), 0.74 (dt, J = 4.8, 8.4 Hz, 1 H), 0.22 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 247.3, 140.2, 137.5, 129.5, 125.8, 125.74, 125.73,

53.2, 20.9, 19.7, 14.5, 13.6, −3.2; IR (ﬁlm) 3065, 2958, 1643, 1249,

847 cm⁻¹; HRMS (EI) m/z 246.1432 [(M⁺), calcd for C₁₅H₂₂OSi,

246.1440]. Spectroscopic data for 4e: ¹H NMR (500 MHz, CDCl₃) δ

7.35 (m, 1 H), 7.16−7.09 (m, 3 H), 6.00 (ddd, J = 2.0, 2.5, 5.5 Hz,

1 H), 5.72 (ddd, J = 1.5, 2.5, 6.0 Hz, 1 H), 3.76 (t, J = 9.0 Hz, 1 H),

2.77 (ddt, A of ABX system, J = 2.5, 9.5, 16.5 Hz, 1 H), 2.71 (dddd, B

of ABX system, J = 1.5, 2.5, 8.5, 16.5 Hz, 1 H), 2.49 (s, 3 H), 1.40 (s,

1 H), −0.28 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 139.5, 138.2,

136.5, 131.3, 130.7, 127.2, 126.4, 125.4, 86.2, 55.0, 38.1, 21.0, −3.4;

IR (ﬁlm) 3440, 3060, 2958, 1247, 839 cm⁻¹; HRMS (ESI) 229.1411

[(M − OH)⁺, calcd for C₁₅H₂₁Si, 229.1413].

2.12 H), 6.97 (d, J = 8.0 Hz, 2.12 H), 4.52 (d, J = 7.0 Hz, 0.06 H), 4.40

(s, 0.06 H), 2.74 (dd, A of ABX system, J = 6.0, 16.0 Hz, 1 H), 2.58

(dd, B of ABX system, J = 7.0, 17.0 Hz, 1 H), 1.84 (m, 0.06 H), 1.68

(m, 0.06 H), 1.61 (dt, J = 5.0, 9.0 Hz, 1 H), 1.27 (m, 1 H), 1.19 (m,

0.06 H), 0.99 (m, 0.06 H), 0.93 (dt, J = 5.0, 8.5 Hz, 1 H), 0.72 (dt,

J = 5.5, 8.5 Hz, 1 H), 0.19 (s, 9 H), 0.12 (s, 0.55 H); ¹³C NMR

(126 MHz, CDCl₃) δ 247.3, 139.7, 135.0, 128.9 (2C), 125.9 (2C),

53.2, 22.4, 20.9, 16.5, 15.4, −3.2; IR (ﬁlm) 3060, 2958, 1643, 1248,

844 cm⁻¹; HRMS (EI) m/z 246.1442 [(M⁺), calcd for C₁₅H₂₂OSi,

246.1440]. Spectroscopic data for 4g: ¹H NMR (500 MHz, CDCl₃) δ

7.26 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 7.5 Hz, 2 H), 5.97 (m, 1 H), 5.75

(ddd, J = 1.5, 2.0, 6.0 Hz, 1 H), 3.39 (dd, J = 8.0, 10.5 Hz, 1 H), 2.70

(m, 1 H), 2.59 (m, 1 H), 2.32 (s, 3 H), −0.30 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 137.2, 136.2, 130.6, 128.8 (2 C), 128.3 (2 C),

84.4, 59.7, 35.5, 21.0, −3.4; IR (ﬁlm) 3443, 2957, 1491, 1247, 839 cm⁻¹;

HRMS (ESI) 229.1407 [(M − OH)⁺, calcd for C₁₅H₂₁Si, 229.1413].

2-(2-(4-Fluorophenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one

(3h) and 5-(4-Fluorophenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol

(4h). Applying general procedure H to 1h (60.3 mg, 0.24 mmol, 1

equiv) and n-butyllithium (1.6 M in hexanes, 0.18 mL, 1.2 equiv) in

THF (3 mL) at −78 °C for 10 min aﬀorded after workup and column

chromatography (5% EtOAc in hexanes) 39.5 mg (66%) of 3h (dr >

20:1) and 6.7 mg (11%) of 4h (dr > 20:1) as colorless oils. Spectro-

scopic data for 3h: ¹H NMR (500 MHz, CDCl₃) δ 7.03 (m, 2 H), 6.90

(m, 2 H), 2.67 (m, 2 H), 1.60 (dt, J = 4.5, 9.0 Hz, 1 H), 1.23 (m, 1 H),

0.90 (dt, J = 5.0, 8.5 Hz, 1 H), 0.72 (dt, J = 5.0, 8.5 Hz, 1 H), 0.18 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 247.1, 161.1 (d, J = 243.4 Hz),

138.3 (d, J = 3.2 Hz), 127.5 (d, J = 7.7 Hz, 2 C), 114.9 (d, J = 21.3 Hz,

2 C), 53.0, 22.1, 16.3, 15.2, −3.2; IR (ﬁlm) 3071, 2959, 1645, 1512,

1250, 844 cm⁻¹; HRMS (EI) m/z 250.1181 [(M⁺), calcd for

C₁₄H₁₉OSiF, 250.1189]. Spectroscopic data for 4h: ¹H NMR

(500 MHz, CDCl₃) δ 7.35 (m, 2 H), 6.98 (m, 2 H), 5.97 (ddd, J =

2.0, 3.0, 5.5 Hz, 1 H), 5.75 (ddd, J = 1.5, 2.5, 6.0 Hz, 1 H), 3.40 (t, J =

8.5 Hz, 1 H), 2.70−2.59 (m, 2 H), −0.30 (s, 9 H); ¹³C NMR (126

MHz, CDCl₃) δ 161.9 (d, J = 245.7 Hz), 137.4, 136.2, 130.5, 129.8 (d,

J = 7.8 Hz, 2 C), 114.8 (d, J = 20.8 Hz, 2 C), 84.2, 59.2, 35.6, −3.4; IR

(ﬁlm) 3431, 3059, 2922, 1510, 839 cm⁻¹; HRMS (EI) m/z 232.1085

[(M − H₂O)⁺, calcd for C₁₄H₁₇SiF, 232.1084].

2-(2-(3-Methylphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one

(3f) and 5-(3-Methylphenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol

(4f). Applying general procedure H to 1f (91.4 mg, 0.371 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.28 mL, 1.2 equiv) in

THF (4.6 mL) at −78 °C for 10 min aﬀorded after workup and

column chromatography (5% and 10% EtOAc in hexanes) 53.5 mg

(59%) of 3f (dr > 20:1) and 27.6 mg (30%) of 4f (dr > 20:1) as

colorless oils. Spectroscopic data for 3f: ¹H NMR (600 MHz, CDCl₃)

δ 7.12 (t, J = 7.2 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.88 (s, 1 H),

6.86 (d, J = 7.8 Hz, 1 H), 2.75 (dd, A of ABX system, J = 6.0, 16.8 Hz,

1 H), 2.58 (dd, B of ABX system, J = 7.2, 16.8 Hz, 1 H), 2.30 (s, 3 H),

1.61 (dt, J = 4.8, 9.0 Hz, 1 H), 1.30 (m, 1 H), 0.97 (dt, J = 5.4, 8.4 Hz,

1 H), 0.73 (dt, J = 5.4, 8.4 Hz, 1 H), 0.19 (s, 9 H); ¹³C NMR (151

MHz, CDCl₃) δ 247.2, 142.7, 137.8, 128.1, 126.6, 126.3, 122.9, 53.1,

22.6, 21.4, 16.6, 15.7, −3.2; IR (ﬁlm) 3066, 2958, 1643, 1249, 844

cm⁻¹; HRMS (EI) m/z 246.1434 [(M⁺), calcd for C₁₅H₂₂OSi,

trans-2-(2-(4-Chlorophenyl)cyclopropyl)-1-(trimethylsilyl)ethan-

1-one (3i) and cis-5-(4-Chlorophenyl)-1-(trimethylsilyl)cyclopent-2-

en-1-ol (4i). Applying general procedure H to 1i (93 mg, 0.349 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.24 mL, 1.1 equiv) in

THF (4.4 mL) at −78 °C for 5 min aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 26 mg (28%) of 3i

(dr = 15:1) and 60.4 mg (65%) of 4i (dr > 20:1) as colorless oils.

Spectroscopic data for 3i: ¹H NMR (500 MHz, CDCl₃) δ 7.18 (d, J =

8.5 Hz, 2 H), 6.99 (d, J = 9.0 Hz, 2 H), 2.66 (d, J = 7.0 Hz, 2 H), 1.59

(dt, J = 5.0, 9.0 Hz, 1 H), 1.25 (m, 1 H), 0.92 (dt, J = 5.0, 8.5 Hz, 1 H),

0.74 (dt, J = 5.5, 8.5 Hz, 1 H), 0.18 (s, 9 H); ¹³C NMR (126 MHz,

CDCl₃) δ 247.0, 141.4, 131.1, 128.3 (2 C), 127.4 (2 C), 53.0, 22.2,

16.7, 15.5, −3.2; IR (ﬁlm) 3072, 2960, 1645, 1496, 1250, 846 cm⁻¹;

HRMS (EI) m/z 266.0891 [(M⁺), calcd for C₁₄H₁₉SiOCl, 266.0894].

1

Spectroscopic data for 4i: H NMR (500 MHz, CDCl₃) δ 7.31 (m,

246.1440]. Spectroscopic data for 4f: H NMR (600 MHz, CDCl₃) δ

2 H), 7.24 (m, 2 H), 5.96 (ddd, J = 2.0, 2.5, 5.5 Hz, 1 H), 5.74 (ddd,

J = 1.0, 2.0, 5.5 Hz, 1 H), 3.38 (dd, J = 8.0, 10.0 Hz, 1 H), 2.66 (ddt, A

of ABX system, J = 2.0, 10.0, 16.0 Hz, 1 H), 2.60 (dddd, B of ABX

system, J = 1.5, 3.0, 8.0, 16.0 Hz, 1 H), 1.50 (s, 1 H), −0.30 (s, 9 H);

¹³C NMR (126 MHz, CDCl₃) δ 139.0, 137.4, 132.4, 130.4, 129.8

(2 C), 128.2 (2 C), 84.2, 59.3, 35.3, 3.4; IR (ﬁlm) 3443, 3054, 2957,

1491, 1247, 838 cm⁻¹; HRMS (ESI) m/z 249.0867 [(M − OH)⁺,

calcd for C₁₄H₁₈SiCl, 249.0866].

7.12 (m, 1 H), 7.17 (m, 2 H), 7.04 (m, 1 H), 5.98 (ddd, J = 1.8, 2.4,

5.4 Hz, 1 H), 5.75 (ddd, J = 1.8, 2.4, 6.0 Hz, 1 H), 3.40 (ddt, J = 7.8,

10.2 Hz, 1 H), 2.72 (ddt, A of ABX system, J = 2.4, 10.8, 16.2 Hz,

1 H), 2.62 (dddd, J = 1.8, 3.0, 8.4, 16.2 Hz, 1 H), 2.33 (s, 3 H), 1.48 (s,

1 H), −0.30 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) δ 140.3, 137.6,

137.2, 130.6, 129.4, 128.0, 127.4, 125.3, 84.4, 59.9, 35.4, 21.4, −3.5;

IR (ﬁlm) 3440, 2957, 1490, 1247, 838 cm⁻¹; HRMS (ESI) 229.1401

[(M − OH)⁺, calcd for C₁₅H₂₁Si, 229.1413].

cis-5-(4-(Triﬂuoromethyl)phenyl)-1-(trimethylsilyl)cyclopent-2-

en-1-ol (4j). Applying general procedure H to 1j (42 mg, 0.1378 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.13 mL, 1.5 equiv) in

THF 1.5 mL) at −78 °C for 30 min aﬀorded after workup and column

chromatography (10% and 15% EtOAc in hexanes) 38 mg (90%) of

2-(2-(4-Methylphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one

(3g) and 5-(4-Methylphenyl)-1-(trimethylsilyl)cyclopent-2-en-1-ol

(4g). Applying general procedure H to 1g (70.6 mg, 0.2865 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.21 mL, 1.2 equiv) in

THF (3.6 mL) at −78 °C for 10 min aﬀorded after workup and

column chromatography (5% and 10% EtOAc in hexanes) 60.3 mg

1

4j (dr > 20:1) as a colorless oil: H NMR (600 MHz, CDCl₃) δ 7.53

V

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(m, 4 H), 5.99 (ddd, J = 1.8, 3.0, 6.0 Hz, 1 H), 5.77 (ddd, J = 1.2, 2.4,

6.0 Hz, 1 H), 3.48 (dd, J = 7.8, 9.6 Hz, 1 H), 2.73 (ddt, A of ABX

system, J = 2.4, 10.8, 16.2 Hz, 1 H), 2.65 (dddd, B of ABX system, J =

1.2, 3.0, 7.8, 15.6 Hz, 1 H), 1.53 (s, 1 H), −0.31 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 144.7, 137.4, 130.3, 129.0 (q, J = 32.3 Hz), 128.8

(2 C), 124.9 (q, J = 3.8 Hz, 2 C), 124.3 (q, J = 272.6 Hz), 84.2, 59.7,

35.2, −3.5; IR (neat) 3441, 1327, 1248, 1165, 1126, 1070, 843 cm⁻¹;

HRMS (ESI) m/z 283.1138 [(M − OH)⁺, calcd for C₁₅H₁₈SiF₃,

283.1130].

16.5 Hz, 1 H), 1.54 (dt, J = 4.5, 9.0 Hz, 1 H), 1.23 (m, 1 H), 0.87 (dt,

J = 5.5, 9.0 Hz, 1 H), 0.64 (dt, J = 5.5, 9.0 Hz, 1 H), 0.49 (s, 3 H), 0.48

(s, 3 H); ¹³C NMR (126 MHz, CDCl₃) δ 245.2, 142.7, 134.3, 134.0

(2 C), 129.9, 128.17 (2 C), 128.16 (2 C), 125.8 (2 C), 125.4, 53.3, 22.6,

16.7, 15.6, −4.79, −4.82; IR (ﬁlm) 3089, 2987, 1642, 1423, 1113,

698 cm⁻¹; HRMS (EI) m/z 294.1440 [(M⁺), calcd for C₁₉H₂₂OSi,

294.1440]. Spectroscopic data for a mixture of 4m and desilylated 3m

1

(1:0.33): H NMR (500 MHz, CDCl₃) δ 9.82 (m, 0.33 H), 7.30 (m,

2.66 H), 7.26−7.20 (m, 8 H), 7.14 (m, 0.33 H), 7.07 (m, 0.66 H), 5.98

(m, 1 H), 5.70 (m, 1 H), 3.44 (t, J = 9.0 Hz, 1 H), 2.59−2.48 (m,

2.33 H), 2.43 (m, 0.33 H), 1.75 (m, 0.33 H), 1.55 (s, 1 H), 1.32 (m,

1 H), 1.06 (m, 0.33 H), 0.87 (m, 0.33 H), 0.00 (s, 3 H), −0.11 (s, 3 H);

¹³C NMR (126 MHz, CDCl₃) δ 140.0, 137.3, 134.5 (3 C), 131.0, 128.9,

128.7 (2 C), 128.0 (2 C), 127.3 (2 C), 126.8, 125.9, 84.2, 59.8,

35.4, −4.9, −5.4; HRMS (ESI) m/z 277.1402 [(M − OH)⁺, calcd for

C₁₉H₂₁Si, 277.1413].

trans-1-(Methyldiphenylsilyl)-2-(2-phenylcyclopropyl)ethan-1-

one (3n). Applying general procedure H to 1n (70 mg, 0.196 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.15 mL, 1.2 equiv)

in THF (2.5 mL) at −78 °C for 10 min aﬀorded after workup and

column chromatography (5% EtOAc in hexanes) 48.6 mg (70%) of 3n

(dr = 20:1) as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.57 (m,

4 H), 7.43 (m, 2 H), 7.37 (m, 4 H), 7.20 (t, J = 7.5 Hz, 2 H), 7.11 (tt,

J = 1.5, 7.5 Hz, 1 H), 6.98 (m, 2 H), 2.77 (dd, A of ABX system, J =

6.0, 17.5 Hz, 1 H), 2.66 (dd, B of ABX system, J = 7.0, 17.0 Hz, 1 H),

1.52 (m, 1 H), 1.26 (m, 1 H), 0.88 (m, 1 H), 0.74 (s, 3 H), 0.63 (dt,

J = 5.5, 9.0 Hz, 1 H); ¹³C NMR (126 MHz, CDCl₃) δ 243.6, 142.8,

135.0 (4 C), 132.61, 132.59, 130.1 (2 C), 128.22 (4 C), 128.18 (2 C),

125.9 (2 C), 125.4, 54.1, 22.6, 16.7, 15.6, −5.3; IR (ﬁlm) 3089, 2990,

1643, 1429, 1113, 698 cm⁻¹; HRMS (EI) m/z 356.1605 [(M⁺), calcd

for C₂₄H₂₄OSi, 356.1596].

trans-2-(2-([1,1′-Biphenyl]-4-yl)cyclopropyl)-1-(trimethylsilyl)-

ethan-1-one (3k) and cis-5-([1,1′-Biphenyl]-4-yl)-1-(trimethylsilyl)-

cyclopent-2-en-1-ol (4k). Applying general procedure H to 2k (66.8 mg,

0.2165 mmol, 1 equiv) and sec-butyllithium (1.4 M in cyclohexane,

0.46 mL, 3 equiv) in THF (2.4 mL) at −78 °C for 3 h aﬀorded after

workup and column chromatography (5% and 10% EtOAc in hexanes)

3.5 mg (5%) of 3k (dr = 7:1) as colorless oil and 50.4 mg (75%) of 4k

1

(dr > 20:1) as a white solid. Spectroscopic data for 3k: H NMR

(500 MHz, CDCl₃) δ 7.54 (m, 2 H), 7.46 (m, 2 H), 7.40 (m, 2 H),

7.30 (m, 1 H), 7.13 (m, 2 H), 2.76 (dd, A of ABX system, J = 6.0,

16.5 Hz, 1 H), 2.62 (dd, B of ABX system, J = 7.0, 17.0 Hz, 1 H), 1.68

(dt, J = 5.0, 9.0 Hz, 1 H), 1.35 (m, 1 H), 1.01 (dt, J = 5.5, 8.5 Hz, 1 H),

0.78 (dt, J = 5.5, 8.5 Hz, 1 H), 0.20 (s, 9 H). Spectroscopic and

melting point data for 4k: mp 75−76 °C; ¹H NMR (500 MHz,

CDCl₃) δ 7.62 (m, 2 H), 7.56 (m, 2 H), 7.48 (m, 2 H), 7.43 (m, 2 H),

7.33 (m, 1 H), 6.01 (ddd, J = 1.5, 2.5, 5.5 Hz, 1 H), 5.80 (ddd, J = 1.5,

2.5, 6.0 Hz, 1 H), 3.49 (dd, J = 8.0, 10.0 Hz, 1 H), 2.78 (ddt, A of ABX

system, J = 2.0, 10.0, 16.0 Hz, 1 H), 2.68 (dddd, B of ABX system, J =

1.0, 3.0, 8.0, 16.0 Hz, 1 H), 1.56 (s, 1 H), −0.25 (s, 9 H); ¹³C NMR

(126 MHz, CDCl₃) δ 140.9, 139.6, 137.3, 130.5, 128.9 (2 C), 128.7

(2 C), 127.1, 126.9 (2 C), 126.7 (2 C), 84.5, 59.7, 35.4, −3.4 (one

aromatic carbon could not be located); IR (ﬁlm) 3442, 3060, 2955,

1246, 839 cm⁻¹; HRMS (EI) m/z 290.1481 [(M − H₂O)⁺, calcd for

C₂₀H₂₂Si, 290.1491].

trans-2-(2-Phenylcyclopropyl)-1-(triethylsilyl)ethan-1-one (3o)

and cis-5-Phenyl-1-(triethylsilyl)cyclopent-2-en-1-ol (4o). Applying

general procedure H to 1o (91.4 mg, 0.333 mmol, 1 equiv) and n-

butyllithium (1.6 M in hexanes, 0.25 mL, 1.5 equiv) in THF (4.2 mL)

at −78 °C for 10 min aﬀorded after workup and column chromato-

graphy (5% and 10% EtOAc in hexanes) 85.2 mg (93%) of 3o (dr >

20:1) and 4 mg (∼5%) of 4o (dr > 20:1) as colorless oils. Spectro-

scopic data for 3o: ¹H NMR (600 MHz, CDCl₃) δ 7.22 (m, 2 H), 7.12

(m, 1 H), 7.06 (m, 2 H), 2.73 (dd, A of ABX system, J = 6.6, 17.4 Hz,

1 H), 2.56 (dd, B of ABX system, J = 7.2, 16.8 Hz, 1 H), 1.62 (dt, J =

4.8, 9.0 Hz, 1 H), 1.33 (m, 1 H), 0.96 (m, heavily overlapped, 1 H),

0.96 (t, J = 7.8 Hz, 9 H), 0.73 (m, heavily overlapped, 1 H), 0.73 (q,

J = 7.8 Hz, 6 H); ¹³C NMR (151 MHz, CDCl₃) δ 247.0, 142.9, 128.2

(2 C), 125.9 (2 C), 125.4, 54.8, 22.6, 16.5, 15.7, −7.2, −2.1; IR (ﬁlm)

3033, 2952, 1644, 1011, 730 cm⁻¹; HRMS (EI) m/z 274.1753 [(M)⁺,

trans-2-(2-(Naphthalen-2-yl)cyclopropyl)-1-(trimethylsilyl)ethan-

1-one (3l) and cis-5-(Naphthalen-2-yl)-1-(trimethylsilyl)cyclopent-

2-en-1-ol (4l). Applying general procedure H to 1l (83.4 mg,

0.295 mmol, 1 equiv) and n-butyllithium (1.6 M in hexanes, 0.22 mL,

1.2 equiv) in THF (3.7 mL) at −78 °C for 10 min aﬀorded after workup

and column chromatography (5% and 10% EtOAc in hexanes) 2.6 mg

(3%) of 3l (dr > 20:1) as a colorless oil and 79.9 mg (96%) of 4l (dr >

1

20:1) as a white solid. Spectroscopic data for 3l: H NMR (600 MHz,

CDCl₃) δ 7.73 (m, 3 H), 7.51 (s, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 7.36 (t,

J = 7.8 Hz, 1 H), 7.20 (d, J = 8.4 Hz, 1 H), 2.77 (dd, A of ABX system,

J = 6.0, 17.0 Hz, 1 H), 2.67 (dd, B of ABX system, J = 6.6, 16.8 Hz,

1 H), 1.80 (m, 1 H), 1.42 (m, 1 H), 1.09 (dt, J = 4.8, 8.4 Hz, 1 H), 0.82

(m, 1 H); ¹³C NMR (151 MHz, CDCl₃) δ 247.2, 140.3, 133.5, 131.9,

127.9, 127.6, 127.3, 125.9, 125.0, 124.9, 124.0, 53.2, 23.0, 16.8, 15.7,

−3.1, −3.5; IR (ﬁlm) 3053, 2957, 1645, 1250, 844 cm⁻¹; HRMS (EI)

m/z 282.1429 [(M⁺), calcd for C₁₈H₂₂OSi, 282.1440]. Spectroscopic

1

calcd for C₁₇H₂₆OSi, 274.1753]. Spectroscopic data for 4o: H NMR

(600 MHz, CDCl₃) δ 7.40 (d, J = 7.8 Hz, 2 H), 7.28 (t, J = 7.8 Hz,

2 H), 7.23 (m, 1 H), 5.95 (m, 1 H), 5.83 (m, 1 H), 3.40 (t, J = 8.4 Hz,

1 H), 2.74 (m, 1 H), 2.64 (m, 1 H), 1.41 (s, 1 H), 0.81 (t, J = 7.8 Hz,

9 H), 0.27 (dq, J = 4.8, 7.8 Hz, 6 H); ¹³C NMR (126 MHz, CDCl₃) δ

140.1, 138.1, 130.5, 128.5 (2 C), 128.1 (2 C), 126.8, 85.9, 60.6, 35.6,

7.8, 2.2; IR (ﬁlm) 3465, 2951, 2878, 1012, 729 cm−¹; HRMS (EI)

m/z 256.1641 [(M − H₂O)⁺, calcd for C₁₇H₂₄Si, 256.1647].

t r a n s - 2 - ( 2 - ( 3 - M e t h o x y p h e n y l ) c y c l o p r o p y l ) - 1 -

(methyldiphenylsilyl)ethan-1-one (3p) and cis-1-(Dimethyl(phenyl)-

silyl)-5-(3-methoxyphenyl)cyclopent-2-en-1-ol (4p). Applying general

procedure H to 1p (75.4 mg, 0.232 mmol, 1 equiv) and n-butyllithium

(1.6 M in hexanes, 0.17 mL, 1.2 equiv) at −78 °C for 10 min aﬀorded

after workup and column chromatography (5% and 10% EtOAc in

hexanes) 41.3 mg (44%) of 3p (dr = 17:1) and 14.3 mg (20%) of 4p

(dr > 20:1). Spectroscopic data for 3p: ¹H NMR (600 MHz, CDCl₃) δ

7.51 (m, 2 H), 7.42−7.34 (m, 3 H), 7.12 (t, J = 7.8 Hz, 1 H), 6.66 (dd,

J = 3.0, 7.8 Hz, 1 H), 6.58 (d, J = 7.2 Hz, 1 H), 6.52 (t, J = 2.4 Hz, 1 H),

3.75 (s, 3 H), 2.69 (dd, A of ABX system, J = 6.0, 16.8 Hz, 1 H), 2.53

(dd, B of ABX system, J = 7.2, 17.4 Hz, 1 H), 1.51 (dt, J = 4.8, 9.0 Hz,

1 H), 1.22 (m, 1 H), 0.86 (dt, J = 5.4, 8.4 Hz, 1 H), 0.62 (dt, J = 5.4, 8.4

Hz, 1 H), 0.48 (s, 3 H), 0.47 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ

245.2, 159.6, 144.5, 134.3, 134.0 (2 C), 129.9, 129.2, 128.2 (2 C), 118.3,

111.5, 110.9, 55.1, 53.2, 22.7, 16.8, 15.8, −4.80, −4.83; IR (ﬁlm) 2957,

1

and melting point data for 4l: mp 58−60 °C; H NMR (600 MHz,

CDCl₃) δ 7.81 (m, 3 H), 7.77 (d, J = 9.0 Hz, 1 H), 7.60 (dd, J = 1.8, 8.4

Hz, 1 H), 7.44 (m, 2 H), 6.04 (ddd, J = 2.4, 3.0, 6.0 Hz, 1 H), 5.82 (dq,

J = 1.2, 6.0 Hz, 1 H), 3.61 (dd, J = 8.4, 10.8 Hz, 1 H), 2.89 (ddt, A of

ABX system, J = 1.8, 10.8, 16.2 Hz, 1 H), 2.73 (dddd, B of ABX system,

J = 1.2, 2.4, 7.8, 15.6 Hz, 1 H), 1.60 (s, 1 H), −0.31 (s, 9 H); ¹³C NMR

(151 MHz, CDCl₃) δ 138.2, 137.5, 133.3, 132.5, 130.5, 128.0, 127.7,

127.6, 127.5, 126.1, 125.9, 125.4, 84.4, 60.1, 35.5, −3.3; IR (ﬁlm) 3437,

3055, 2957, 2855, 1246, 839 cm⁻¹; HRMS (EI) m/z 264.1326

[(M − H₂O)⁺, calcd for C₁₈H₂₀Si, 264.1334].

trans-1-(Dimethylphenylsilyl)-2-(2-phenylcyclopropyl)ethan-1-

one (3m) and cis-1-(Dimethylphenylsilyl)-5-phenylcyclopent-2-en-

1-ol (4m). Applying general procedure H to 1m (80.4 mg, 0.273 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.26 mL, 1.5 equiv) in

THF (2.9 mL) at −78 °C for 10 min aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 55 mg (69%) of 3m

(dr > 20:1) as a colorless oil and 6 mg (∼6%) of 4m (dr > 20:1)

contaminated with desilylated 3m as a colorless oil. Spectroscopic data

for 3m: ¹H NMR (500 MHz, CDCl₃) δ 7.53 (m, 2 H), 7.42−7.36 (m,

3 H), 7.21 (m, 2 H), 7.11 (m, 1 H), 7.00 (m, 2 H), 2.70 (dd, A of ABX

system, J = 6.5, 17.0 Hz, 1 H), 2.57 (dd, B of ABX system, J = 7.0,

W

DOI: 10.1021/jo5026942

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

1645, 844 cm⁻¹; HRMS (EI) m/z 324.1546 [(M⁺), calcd for C₂₀H₂₄O₂Si,

324.1546]. Spectroscopic data for 4p: H NMR (600 MHz, CDCl₃) δ

127.3, 125.9, 125.0, 124.9, 124.0, 54.8, 22.9, 16.5, 15.7, 7.3, 2.1; IR

(ﬁlm) 3055, 2955, 2876, 1639, 1018, 910, 740 cm⁻¹; HRMS (EI) m/z

324.1901 [(M)⁺, calcd for C₂₁H₂₈OSi, 324.1909]. Spectroscopic data

1

7.30 (m, 3 H), 7.23 (m, 2 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.87 (m, 1 H),

6.79 (s, 1 H), 6.75 (dd, J = 2.4, 8.4 Hz, 1 H), 5.97 (m, 1 H), 5.71 (m,

1 H), 3.70 (s, 3 H), 3.42 (dd, J = 8.4, 10.2 Hz, 1 H), 2.58−2.48 (m, 2 H),

1.59 (s, 1 H), 0.05 (s, 3 H), −0.05 (s, 3 H); ¹³C NMR (151 MHz,

CDCl₃) δ 159.3, 141.6, 137.3, 137.0, 134.5 (2 C), 131.0, 128.92, 128.89,

127.3 (2 C), 121.0, 114.5, 112.3, 84.1, 59.7, 55.1, 35.4, −4.9, −5.2; IR

(ﬁlm) 3440, 3030, 2957, 1250, 819 cm⁻¹; HRMS (EI) m/z 306.1436

[(M − H₂O)⁺, calcd for C₂₀H₂₂OSi, 306.1440].

1

for 4s: H NMR (500 MHz, CDCl₃) δ 7.80 (m, 3 H), 7.76 (d, J =

8.5 Hz, 1 H), 7.61 (dd, J = 1.0, 8.5 Hz, 1 H), 7.44 (m, 2 H), 6.00 (m,

1 H), 5.88 (m, 1 H), 3.57 (m, 1 H), 2.87 (m, 1 H), 2.73 (m, 1 H), 0.77

(t, J = 8.0 Hz, 9 H), 0.26 (dq, J = 1.5, 8.0 Hz, 6 H); ¹³C NMR

(126 MHz, CDCl₃) δ 138.5, 138.3, 133.3, 132.5, 130.5, 127.9, 127.7,

127.6, 127.4, 126.2, 125.8, 125.3, 85.9, 60.7, 35.8, 7.8, 2.3; IR (ﬁlm)

3053, 2951, 2876, 1458, 1012, 819, 727 cm⁻¹; HRMS (ESI) m/z

307.1869 [(M − OH)⁺, calcd for C₂₁H₂₇Si, 307.1882].

trans-2-(2-(4-Chlorophenyl)cyclopropyl)-1-(methyldiphenylsilyl)-

ethan-1-one (3q) and cis-5-(4-Chlorophenyl)-1-(dimethyl(phenyl)-

silyl)cyclopent-2-en-1-ol (4q). Applying general procedure H to 1q

(83 mg, 0.2524 mmol, 1 equiv) and n-butyllithium (1.6 M in hexanes,

0.17 mL, 1.1 equiv) at −78 °C for 5 min aﬀorded after workup and

column chromatography (5% and 10% EtOAc in hexanes) 38.4 mg

(47%) of 3q (dr > 20:1) and 36.1 mg (44%) of 4q (dr > 20:1).

trans-2-(2-(2-Propylphenyl)cyclopropyl)-1-(trimethylsilyl)ethan-

1-one (3t) and cis-5-(2-Propylphenyl)-1-(trimethylsilyl)cyclopent-2-

en-1-ol (4t). Applying general procedure H to 1t (26.6 mg, 0.097 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 73 μL, 1.2 equiv) in THF

(1.2 mL) at −78 °C for 10 min aﬀorded after workup and column chro-

matography (5% EtOAc in hexanes) 15.4 mg (64%) of 3t (dr > 20:1)

and 3 mg (6%) of 4t (dr > 20:1) as colorless oils. Spectroscopic data for

3t: ¹H NMR (500 MHz, CDCl₃) δ 7.09 (m, 3 H), 7.01 (m, 1 H), 2.86

(dd, A of ABX system, J = 5.5, 16.5 Hz, 1 H), 2.69 (m, 2 H), 2.57 (dd, B

of ABX system, J = 7.5, 17.0 Hz, 1 H), 1.68 (dt, J = 5.0, 9.0 Hz, 1 H),

1.62 (m, 2 H), 1.34 (m, 1 H), 0.98 (t, J = 7.0 Hz, 3 H), 0.92 (dt, J = 5.0,

8.5 Hz, 1 H), 0.74 (dt, J = 5.5, 8.5 Hz, 1 H), 0.20 (s, 9 H); ¹³C NMR

(126 MHz, CDCl₃) δ 247.3, 141.7, 139.8, 128.7, 125.9, 125.7, 125.6,

53.3, 35.2, 23.8, 20.3, 14.9, 14.3, 14.2, −3.2; IR (ﬁlm) 3064, 2959, 2872,

1645, 1250, 844 cm⁻¹; HRMS (EI) m/z 274.1739 [(M⁺), calcd for

1

Spectroscopic data for 3q: H NMR (600 MHz, CDCl₃) δ 7.51 (m,

2 H), 7.41 (m, 1 H), 7.36 (m, 2 H), 7.15 (m, 2 H), 6.90 (m, 2 H), 2.61

(m, 2 H), 1.48 (dt, J = 4.8, 9.0 Hz, 1 H), 1.16 (m, 1 H), 0.82 (dt, J =

5.4, 9.0 Hz, 1 H), 0.63 (dt, J = 5.4, 9.0 Hz, 1 H), 0.48 (s, 3 H), 0.47 (s,

3 H); ¹³C NMR (151 MHz, CDCl₃) δ 245.1, 141.3, 134.3, 134.0 (2C),

131.0, 129.9, 128.23 (2C), 128.20 (2 C), 127.3 (2 C), 53.1, 22.1, 16.8,

15.5, −4.8, −4.9; IR (ﬁlm) 3030, 2958, 1641, 1490, 1012, 823, 734 cm⁻¹;

HRMS (EI) m/z 328.1049 [(M⁺), calcd for C₁₉H₂₁OSiCl, 328.1050].

1

Spectroscopic data for 4q: H NMR (600 MHz, CDCl₃) δ 7.31 (m,

1

C₁₇H₂₆OSi, 274.1753]. Spectroscopic data for 4t: H NMR (500 MHz,

1 H), 7.27 (m, 2 H), 7.23 (m, 2 H), 7.15 (m, 4 H), 5.98 (ddd, J = 1.8,

3.0, 6.0 Hz, 1 H), 5.73 (ddd, J = 1.2, 2.4, 6.0 Hz, 1 H), 3.39 (dd, J = 7.2,

10.2 Hz, 1 H), 2.55 (dddd, A of ABX system, J = 1.2, 3.0, 7.8, 15.6 Hz,

1 H), 2.45 (ddt, B of ABX system, J = 2.4, 10.2, 18.0 Hz, 1 H), 1.56 (s,

1 H), 0.04 (s, 3 H), −0.03 (s, 3 H); ¹³C NMR (151 MHz, CDCl₃) δ

138.5, 137.4, 136.5, 134.3 (2 C), 132.4, 131.0, 129.9 (2 C), 129.0, 128.0

(2 C), 127.4 (2 C), 84.2, 59.0, 35.3, −4.8, −5.2; IR (ﬁlm) 3440, 2950,

1246, 820 cm⁻¹; HRMS (EI) m/z 310.0946 [(M − H₂O)⁺, calcd for

C₁₉H₁₉SiCl, 310.0945].

CDCl₃) δ 7.34 (m, 1 H), 7.16−7.10 (m, 3 H), 6.02 (dt, J = 2.5, 5.5 Hz,

1 H), 5.74 (dt, J = 2.0, 6.0 Hz, 1 H), 3.81 (t, J = 8.5 Hz, 1 H), 3.11 (ddd,

J = 6.5, 8.5, 14.0 Hz, 1 H), 2.80−2.69 (m, 2 H), 2.54 (ddd, J = 7.0, 9.5,

14.0 Hz, 1 H), 1.58 (m, 2 H), 0.96 (t, J = 7.0 Hz, 3 H), −0.28 (s, 9 H);

IR (ﬁlm) 3444, 3058, 2957, 1490, 1246, 838 cm⁻¹; HRMS (EI) m/z

274.1739 [(M⁺), calcd for C₁₇H₂₆OSi, 274.1753].

cis-2-Methyl-5-phenyl-1-(trimethylsilyl)cyclopent-2-en-1-ol (4u).

Applying general procedure H to 2u (200 mg, 0.81 mmol, 1 equiv)

and sec-butyllithium (1.4 M in cyclohexane, 1.8 mL, 3 equiv) at −78 °C

for 7 h aﬀorded after workup and column chromatography (10% EtOAc

trans-2-(2-(4-Chlorophenyl)cyclopropyl)-1-(triethylsilyl)ethan-1-

one (3r) and cis-5-(4-Chlorophenyl)-1-(triethylsilyl)cyclopent-2-en-

1-ol (4r). Applying general procedure H to 1r (69.5 mg, 0.225 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.15 mL, 1.1 equiv) in

THF (2.8 mL) at −78 °C for 5 min aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 43.7 mg (63%) of

3r (dr > 20:1) and 15.7 mg (23%) of 4r (dr > 20:1). Spectroscopic

1

in hexanes) 157.7 mg (79%) of 4u (dr = 20:1) as a colorless oil: H

NMR (500 MHz, CDCl₃) δ 7.38 (m, 2 H), 7.27 (m, 2 H), 7.22 (m,

1 H), 5.64 (m, 1 H), 3.41 (m, 1 H), 2.63 (m, 1 H), 2.43 (m, 1 H), 1.76

(m, 3 H), 1.40 (s, 1 H), −0.30 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃)

δ 145.7, 140.9, 128.7 (2 C), 128.1 (2 C), 126.8, 124.8, 84.8, 61.8, 32.9,

14.6, −2.2; IR (ﬁlm) 3440, 2957, 1243, 838 cm⁻¹; HRMS (ESI) m/z

229.1401 [(M − OH)⁺, calcd for C₁₅H₂₁Si, 229.1413].

1

data for 3r: H NMR (600 MHz, CDCl₃) δ 7.18 (m, 2 H), 7.00 (m,

2 H), 2.68−2.60 (m, 2 H), 1.57(dt, J = 5.6, 9.0 Hz, 1 H), 1.27 (m,

1 H), 0.95 (t, J = 7.8 Hz, 9 H), 0.92 (m, 1 H, overlapped), 0.73 (m,

1 H, heavily overlapped), 0.72 (q, J = 7.8 Hz, 6 H); ¹³C NMR

(151 MHz, CDCl₃) δ 246.9, 141.4, 131.0, 128.3 (2 C), 127.4 (2 C),

54.7, 22.2, 16.5, 15.5, 7.2, 2.1; IR (ﬁlm) 2955, 2878, 1641, 1495, 1012,

823, 734 cm⁻¹; HRMS (EI) m/z 308.1357 [(M⁺), calcd for C₁₇H₂₅OSiCl,

5-(4-Methoxyphenyl)-2-methyl-1-(trimethylsilyl)cyclopent-2-en-

1-ol (4v). Applying general procedure H to 1v (61.5 mg, 0.2225 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.17 mL, 1.2 equiv) at

−78 °C for 35 min aﬀorded after workup and column chromatography

(10% EtOAc in hexanes) 44 mg (72%) of 4v (dr = 20:1) as a white

1

308.1363]. Spectroscopic data for 4r: H NMR (600 MHz, CDCl₃) δ

solid: mp 96−97 °C; H NMR (500 MHz, CDCl₃) δ 7.29 (m, 2 H),

7.34 (m, 2 H), 7.24 (m, 2 H), 5.94 (m, 1 H), 5.82 (ddd, J = 1.2, 2.4, 6.0

Hz, 1 H), 3.35 (t, J = 8.4 Hz, 1 H), 2.69−2.60 (m, 2 H), 0.82 (t, J = 7.8

Hz, 9 H), 0.28 (m, 6 H); ¹³C NMR (151 MHz, CDCl₃) δ 139.3, 138.2,

132.3, 130.4, 129.8 (2 C), 128.1 (2 C), 85.7, 59.9, 35.6, 7.8, 2.3; IR (ﬁlm)

3439, 3053, 2953, 2878, 1493, 1093, 1014, 825, 717 cm⁻¹; HRMS (EI)

m/z 290.1249 [(M − H₂O)⁺, calcd for C₁₇H₂₃SiCl, 290.1258].

trans-2-(2-(Naphthalen-2-yl)cyclopropyl)-1-(triethylsilyl)ethan-1-

one (3s) and cis-5-(Naphthalen-2-yl)-1-(triethylsilyl)cyclopent-2-en-

1-ol (4s). Applying general procedure H to 2s (133.5 mg, 0.411 mmol,

1 equiv) and sec-butyllithium (1.4 M in cyclohexane, 1.5 mL, 5 equiv)

at −78 °C, and then at 0 °C for 6 h, aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 58.8 mg (45%) of

3s (dr = 3.2:1) and 11.8 mg (9%) of 4s (dr > 20:1) as colorless oils.

Spectroscopic data for 3s (major diastereomer (trans)): ¹H NMR

(500 MHz, CDCl₃) δ 7.76−7.70 (m, 3 H), 7.51 (s, 1 H), 7.43−7.34

(m, 2 H), 7.20 (dd, J = 2.0, 8.5 Hz, 1 H), 2.77 (dd, A of ABX system,

J = 6.0, 17.0 Hz, 1 H), 2.62 (dd, B of ABX system, J = 7.0, 17.4 Hz,

1 H), 1.79 (quintet, J = 4.5 Hz, 1 H), 1.44 (m, 1 H), 1.10 (m, 1 H,

0.96 (t, J = 7.5 Hz, 9 H), 0.81 (m, 1 H), 0.74 (q, J = 7.5 Hz, 6 H); ¹³C

NMR (126 MHz, CDCl₃) δ 247.1, 140.4, 135.5, 131.9, 127.8, 127.5,

6.82 (m, 2 H), 5.62 (m, 1 H), 3.78 (s, 3 H), 3.34 (dd, J = 7.5, 10.5 Hz,

1 H), 2.58 (m, 1 H), 2.41 (m, 1 H), 1.75 (dt, J = 1.5, 3.0 Hz, 3 H),

1.37 (s, 1 H), −0.29 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 158.5,

145.6, 132.9, 129.5 (2 C), 124.8, 113.5 (2 C), 84.8, 61.0, 55.2, 33.1,

14.6, −2.1; IR (ﬁlm) 3435, 2952, 1240, 838 cm⁻¹; HRMS (ESI) m/z

259.1507 [(M − OH)⁺, calcd for C₁₆H₂₃OSi, 259.1518].

cis-2-Methyl-5-(4-methylphenyl)-1-(trimethylsilyl)cyclopent-2-en-

1-ol (4w). Applying general procedure H to 1w (66.6 mg, 0.2557 mmol,

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.19 mL, 1.2 equiv) at

−78 °C for 15 min aﬀorded after workup and column chromatography

(10% EtOAc in hexanes) 60.2 mg (91%) of 4w (dr = 20:1) as a

colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 7.26 (d, J = 8.0 Hz, 2 H),

7.08 (d, J = 8.0 Hz, 2 H), 5.63 (quintet, J = 1.5 Hz, 1 H), 3.36 (dd, J =

8.0, 11.0 Hz, 1 H), 2.61 (m, 1 H), 2.41 (m, 1 H), 2.32 (s, 3 H), 1.76 (m,

3 H), 1.37 (s, 1 H), −0.30 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

145.6, 137.7, 136.2, 128.8 (2 C), 128.5 (2 C), 124.8, 84.8, 61.4, 33.0,

21.0, 14.6, −2.2; IR (ﬁlm) 3434, 2953, 1246, 830 cm⁻¹; HRMS (ESI)

m/z 243.1568 [(M − OH)⁺, calcd for C₁₆H₂₃Si, 243.1569].

cis-5-Phenyl-2-(prop-1-en-2-yl)-1-(trimethylsilyl)cyclopent-2-en-

1-ol (4x). Applying general procedure H to 1x (120 mg, 0.445 mmol,

X

DOI: 10.1021/jo5026942

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The Journal of Organic Chemistry

Article

1 equiv) and n-butyllithium (1.6 M in hexanes, 0.56 mL, 2 equiv) at

−78 °C for 1.5 h aﬀorded after workup and column chromatography

(4% EtOAc in hexanes) 16.3 mg (13%) of unreacted 1x and 90 mg

2.23 (m, 0.6 H), 1.81 (m, 1 H), 1.48 (m, 0.6 H), 1.33 (m, 1 H), 1.17

(dt, J = 5.5, 8.5 Hz, 0.6 H), 0.99 (dt, J = 5.0, 8.5 Hz, 1 H), 0.77 (dt, J =

5.0, 8.5 Hz, 1 H), 0.63 (q, J = 5.5 Hz, 0.6 H), 0.19 (s, 9 H), 0.04 (s,

5.4 H); ¹³C NMR (126 MHz, CDCl₃) (major diastereomer) δ 246.9,

147.2, 126.7, 122.8, 122.1, 52.7, 17.9, 17.5, 16.4, −3.2; (minor diaste-

reomer) δ 247.5, 143.5, 126.6, 125.5, 123.4, 47.6, 14.9, 13.2, 11.9,

−3.4; IR (ﬁlm) 3071, 2959, 1645, 1250, 846 cm⁻¹; HRMS (ESI) m/z

239.0922 [(M + H)⁺, calcd for C₁₂H₁₉OSiS, 239.0926]. Spectroscopic

data for 4aa: ¹H NMR (500 MHz, CDCl₃) δ 6.35 (dd, J = 2.0, 6.5 Hz,

1 H), 6.07 (m, 1 H), 5.83 (ddd, J = 3.5, 8.5, 12.0 Hz, 1 H), 5.66 (ddd,

J = 1.0, 3.0, 6.5 Hz, 1 H), 5.42 (dd, J = 3.0, 7.0 Hz, 1 H), 4.40 (m, 1

H), 2.81 (m, 1 H), 2.46 (quintet, J = 3.5 Hz, 1 H), 1.59 (s, 1 H), 0.15

(s, 9 H); ¹³C NMR (600 MHz, CDCl₃) δ 140.8, 131.8, 129.1, 126.3,

123.1, 122.7, 67.8, 57.2, 26.4, −2.3; IR (ﬁlm) 3418, 3017, 2955, 1246,

839 cm⁻¹; HRMS (ESI) m/z 221.0821 [(M − OH)⁺, calcd for

C₁₂H₁₇SiS, 221.0820].

cis-5-(Furan-2-yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4bb). Ap-

plying general procedure H to 1bb (93.8 mg, 0.422 mmol, 1 equiv)

and n-butyllithium (1.6 M in hexanes, 0.29 mL, 1.2 equiv) at −78 °C

for 10 min aﬀorded after workup and column chromatography (10%

EtOAc in hexanes) 76 mg (81%) of 4bb (dr = 20:1) as a colorless oil:

¹H NMR (500 MHz, CDCl₃) δ 6.50 (dd, J = 2.0, 3.0 Hz, 1 H), 5.84

(dddd, J = 0.5, 3.5, 7.5, 12.0 Hz, 1 H), 5.63 (ddd, J = 0.5, 3.0, 12.0 Hz,

1 H), 5.46 (m, 1 H), 5.15 (m, 1 H), 4.11 (m, 1 H), 2.82 (d of quintets,

A of ABX system, J = 3.5, 20.0 Hz, 1 H), 2.50 (dt, B of ABX system,

J = 7.5, 20.0 Hz, 1 H), 0.13 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ

157.4, 145.3, 132.1, 131.1, 103.8. 100.4, 64.9, 50.3, 24.5, −2.6; IR

(ﬁlm) 3499, 3013, 2955, 1246, 1151, 839 cm⁻¹; HRMS (EI) m/z

222.1068 [(M⁺), calcd for C₁₂H₁₈O₂Si, 222.1076].

2-(2-(Furan-2-yl)cyclopropyl)-1-(trimethylsilyl)ethan-1-one (3bb).

Applying general procedure H to 2bb (56.6 mg, 0.255 mmol, 1 equiv)

and sec-butyllithium (1.6 M in cyclohexane, 0.55 mL, 3 equiv) at

−78 °C for 3.5 h aﬀorded after workup and column chromatography

(5% EtOAc in hexanes) 21.2 mg (37%) of 3bb (dr = 1:0.7) as a

colorless oil and 12.9 (23%) of unreacted 2bb (single diastereomer):

mixture of diastereomers (1:0.7); ¹H NMR (600 MHz, CDCl₃) δ 7.23

(m, 1 H), 7.20 (m, 0.7 H), 6.24 (m, 1 H), 6.22 (m, 0.7 H), 5.94 (m,

1 H), 5.92 (m, 1 0.7 H), 2.70 (dd, A of ABX system, J = 6.6, 17.4 Hz,

0.7 H), 2.54 (dd, B of ABX system, J = 7.2, 16.8 Hz, 0.7 H), 2.50 (dd,

C of CDX system, J = 7.2, 18.0 Hz, 1 H), 2.39 (dd, D of CDX system,

J = 6.0, 18.0 Hz, 1 H), 2.05 (dt, J = 6.0, 9.0 Hz, 1 H), 1.64 (dt, J = 4.8,

8.0 Hz, 0.7 H), 1.43 (m, 1 H), 1.38 (m, 0.7 H), 1.10 (dt, J = 4.8,

8.4 Hz, 1 H), 1.03 (dt, J = 4.8, 9.0 Hz, 0.7 H), 0.66 (m, 1.7 H), 0.18 (s,

6.3 H), 0.08 (s, 9 H); ¹³C NMR (151 MHz, CDCl₃) (major

diastereomer) δ 247.3, 154.4, 141.0, 110.1, 106.5, 47.7, 13.3, 12.6, 10.1,

−3.2; (minor diastereomer) δ 246.9, 156.2, 140.4, 110.2, 103.6, 52.5,

15.8, 14.5, 13.3, −3.1; IR (ﬁlm) 2961, 1645, 1250, 844 cm⁻¹; HRMS

(EI) m/z 222.1086 [(M⁺), calcd for C₁₂H₁₈O₂Si, 222.1076].

Preparation of Optically Active Substrates (−)-1a and (+)-2a.

Enzymatic Kinetic Resolution of ( )-α-(Trimethylsilyl)allyl Alcohol

S2-a.⁸²A high-pressure glass tube was charged with racemic α-(tri-

methylsilyl)allyl alcohol S2-a (2.4 g, 18.43 mmol, 1 equiv), vinyl acetate

(2.4 g, 27.65 mmol, 1.5 equiv), and pentane (10 mL). Powdered 4 Å

molecular sieves (1.4 g) and lipase Candida antarctica (15 mg/mmol of

alcohol) were added. The tube was sealed and heated in an oil bath at

40 °C. After 34 h the reaction was cooled at room temperature, ﬁltered

through a plug of Celite, and rinsed with pentane, and the ﬁltrate was

carefully concentrated. Column chromatography (5%, 10% and 15%

Et₂O in pentane) aﬀorded 1.06 g (34%) of (S)-1-(trimethylsilyl)allyl

1

(75%) of 4x (dr = 20:1) as a colorless oil: H NMR (500 MHz,

CDCl₃) δ 7.45 (m, 2 H), 7.30 (m, 2 H), 7.24 (tt, J = 1.5, 7.0 Hz, 1 H),

5.96 (dd, J = 2.5, 3.5 Hz, 1 H), 5.63 (d, J = 1.0 Hz, 1 H), 4.98 (s, 1 H),

3.53 (dd, J = 8.0, 12.0 Hz, 1 H), 2.71 (dd, J = 11.5, 16.5 Hz, 1 H), 2.49

(ddd, J = 3.5, 7.5, 16.5 Hz, 1 H), 1.94 (s, 3 H), 1.67 (s, 1 H), 0.32 (s,

9 H); ¹³C NMR (126 MHz, CDCl₃) δ 148.5, 140.1, 139.0, 128.7

(2 C), 128.1 (2 C), 126.9, 115.1, 85.2, 62.2, 31.7, 23.1, −1.7; IR (ﬁlm)

3443, 3029, 2956, 1242, 833 cm⁻¹; HRMS (ESI) m/z 255.1562

[(M − OH)⁺, calcd for C₁₇H₂₃Si, 255.1569].

trans-2-(1-Methyl-2-phenylcyclopropyl)-1-(trimethylsilyl)ethan-

1-one (3y) and cis-3-Methyl-5-phenyl-1-(trimethylsilyl)cyclopent-2-

en-1-ol (4y). Applying general procedure H to 1y (51.3 mg,

0.208 mmol, 1 equiv) and n-butyllithium (1.6 M in hexanes,

0.16 mL, 1.2 equiv) at −78 °C for 30 min aﬀorded after workup and

column chromatography (5% and 10% EtOAc in hexanes) 22.5 mg

(44%) of 3y (dr = 7:1) and 19.6 mg (38%) of 4y (dr = 20:1) as

colorless oils. Spectroscopic data for 3y: ¹H NMR (500 MHz, CDCl₃) δ

7.27 (m, 4 H), 7.16 (m, 1 H), 2.91 (d, J = 17.5 Hz, 1 H), 2.52 (d, J =

17.5 Hz, 1 H), 1.89 (dd, J = 6.5, 8.5 Hz, 1 H), 0.81 (m, 2 H), 0.73 (s,

3 H), 0.20 (s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 247.9, 139.5,

129.4, 128.9, 127.9, 125.8, 58.6, 28.2, 18.8, 18.5, 17.1, −3.3; IR (ﬁlm)

3061, 2959, 1647, 1250, 844 cm⁻¹; HRMS (EI) m/z 246.1436 [(M⁺),

1

calcd for C₁₅H₂₂OSi, 246.1440]. Spectroscopic data for 4y: H NMR

(500 MHz, CDCl₃) δ 7.37 (m, 2 H), 7.28 (m, 2 H), 7.21 (m, 1 H), 5.38

(m, 1 H), 3.47 (dd, J = 8.0, 10.0 Hz, 1 H), 2.68 (m, 1 H), 2.51 (dd, J =

8.0, 15.5 Hz, 1 H), 1.84 (m, 3 H), 1.42 (s, 1 H), −0.33 (s, 9 H); ¹³C

NMR (126 MHz, CDCl₃) δ 141.2, 140.8, 130.7, 128.4 (2C), 128.1

(2C), 126.7, 84.4, 60.4, 39.6, 17.2, −3.3; IR (ﬁlm) 3437, 3034, 2912,

1244, 837, 758 cm⁻¹; HRMS (ESI) m/z 229.1413 [(M − OH)⁺, calcd

for C₁₅H₂₁Si, 229.1412].

trans-2-(1-Methyl-2-(4-methylphenyl)cyclopropyl)-1-

(trimethylsilyl)ethan-1-one (3z) and cis-3-Methyl-5-(4-methylphen-

yl)-1-(trimethylsilyl)cyclopent-2-en-1-ol (4z). Applying general pro-

cedure H to 1z (50.3 mg, 0.193 mmol, 1 equiv) and n-butyllithium

(1.6 M in hexanes, 0.145 mL, 1.2 equiv) at −78 °C for 15 min aﬀorded

after workup and column chromatography (5% and 10% EtOAc in

hexanes) 21.8 mg (44%) of 3z (dr = 9:1) and 21.5 mg (43%) of 4z

1

(dr = 20:1) as colorless oils. Spectroscopic data for 3z: H NMR

(600 MHz, CDCl₃) δ 7.16 (d, J = 7.8 Hz, 2 H), 7.07 (d, J = 7.8 Hz,

2 H), 2.88 (d, J = 17.4 Hz, 1 H), 2.52 (d, J = 16.8 Hz, 1 H), 2.30 (s,

3 H), 1.85 (t, J = 7.2 Hz, 1 H), 0.76 (m, 2 H), 0.72 (s, 3 H), 0.20 (s,

9 H); ¹³C NMR (151 MHz, CDCl₃) δ 248.0, 136.3, 135.2, 129.3 (2C),

128.6 (2C), 58.7, 27.8, 21.0, 18.8, 18.3, 17.0, −3.2; IR (ﬁlm) 3051,

2957, 2868, 1647, 1250, 844 cm⁻¹; HRMS (EI) m/z 260.1599 [(M⁺),

1

calcd for C₁₆H₂₄OSi, 260.1596]. Spectroscopic data for 4z: H NMR

(600 MHz, CDCl₃) δ 7.25 (d, J = 7.8 Hz, 2 H), 7.08 (d, J = 7.8 Hz,

2 H), 5.37 (s, 1 H), 3.42 (t, J = 8.4 Hz, 1 H), 2.65 (dd, A of ABX

system, J = 9.8, 15.0 Hz, 1 H), 2.49 (dd, B of ABX system, J = 7.2, 15.6

Hz, 1 H), 2.31 (s, 3 H), 1.83 (s, 3 H), 1.40 (s, 1 H), −0.32 (s, 9 H);

¹³C NMR (151 MHz, CDCl₃) δ 141.2, 137.7, 136.1, 130.6, 128.8

(2C), 128.3 (2C), 84.5, 60.0, 39.7, 21.0, 17.2, −3.3; IR (ﬁlm) 3434,

3020, 2961, 2853, 1244, 837 cm⁻¹; HRMS (EI) m/z 242.1502

[(M − H₂O)⁺, calcd for C₁₆H₂₂Si, 242.1491].

trans-2-(2-(Thiophene-2-yl)cyclopropyl)-1-(trimethylsilyl)ethan-

1-one (3aa) and cis-5-(Thiophene-2-yl)-1-(trimethylsilyl)cyclopent-

2-en-1-ol (4aa). Applying general procedure H to 1aa (108 mg,

0.453 mmol, 1 equiv) and n-butyllithium (1.6 M in hexanes, 0.34 mL,

1.2 equiv) at −78 °C for 10 min aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 78.8 mg (73%) of

3aa (dr = 2.1:1) and 25.9 mg (24%) of 4aa (dr = 3.2:1) as colorless

oils. Spectroscopic data for 3aa: mixture of diastereomers (1.0:0.6); ¹H

NMR (500 MHz, CDCl₃) δ 7.05 (dd, J = 1.0, 5.0 Hz, 0.6 H), 7.01 (dd,

J = 1.0, 5.5 Hz, 1 H), 6.87 (dd, J = 3.0, 5.0 Hz, 0.6 H), 6.85 (dd, J =

3.5, 5.0 Hz, 1 H), 6.75 (m, 1 H), 6.67 (dt, J = 1.0, 3.5 Hz, 0.6 H), 2.71

(dd, A of ABX system, J = 6.0, 16.5 Hz, 1 H), 2.60 (dd, B of ABX

system, J = 7.0, 17.5 Hz, 1 H), 2.45 (dd, C of CDX system, J = 8.0,

18.5 Hz, 0.6 H), 2.39 (dd, D of CDX system, J = 6.0, 18.5 Hz, 0.6 H),

acetate (ee not determined) and 786 mg (31%) of (R)-S2-a ([α]_D

=

−6.1 (c = 1, CHCl₃, 76% ee)). The enantiomeric excess (ee) was

determined by HPLC (OJ column, hexanes, 0.6 mL/min, 10 °C).

Preparation of (+)-syn-S3-a and (+)-anti-S3-a by Etheriﬁcation

of (R)-1-(Trimethylsilyl)prop-2-en-1-ol (S2-a). Applying general pro-

cedure D to S2-a (76% ee, 180 mg, 1.382 mmol, 1 equiv), the trichlo-

roacetimidate of 1-phenylbut-3-en-1-ol (606 mg, 2.07 mmol, 1.5 equiv),

and (TMS)OTf (25 μL, 0.138 mmol, 0.1 equiv) in hexane (8 mL)

aﬀorded after column chromatography (7% CH₂Cl₂in hexanes) a total

of 222.5 (62%) of (+)-syn-S3a/(+)-anti-S3-a distributed in three

fractions: 79.2 mg of (+)-anti S3-a ([α]_D= +112 (c = 0.96, CHCl₃)),

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The Journal of Organic Chemistry

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87.3 mg of (+)-syn-S3-a ([α]_D= +2 (c = 0.92, CHCl₃)), and 56 mg

of a mixture of (+)-syn-S3a/(+)-anti-S3-a as a colorless oil. The

enantiomeric excess of both diastereomers could not be determined by

chiral HPLC or GC.

0.222 mmol, 1 equiv) in THF (2 mL) was added via syringe quickly to

give a yellow solution. After 1 h benzoyl chloride (52 μL, 0.444 mmol,

2 equiv) was added, and the temperature kept at −78 °C for 30 min

and then raised to room temperature. The reaction was quenched by

adding NaHCO₃(satd) and diluted with diethyl ether. The aqueous

phase was extracted with diethyl ether (3 × 5 mL). Combined organic

extracts were washed with brine, dried over MgSO₄, and concentrated.

Column chromatography (5% EtOAc in hexanes) aﬀorded 40 mg

(54%) of enol benzoate as an oil. Ozonolysis: A solution of the benzo-

ate (19 mg, 0.056 mmol, 1 equiv) in CH₂Cl₂was cooled at −78 °C.

Bubbling of ozone was applied for 15 min (a slightly blue color

persisted), and then dimethyl sulﬁde (0.1 mL, excess) was added. After

an additional 15 min, the cold bath was removed and the solvent was

removed by rotary evaporation. Column chromatography (15% EtOAc

in hexanes) aﬀorded 4.2 mg (56%) of the known compound

Preparation of (−)-1a and (+)-2a by Ring-Closing Metathesis of

(+)-syn-S3-a and (+)-anti-S3-a. Applying general procedure F to

(+)-syn-S3a/(+)-anti-S3-a (∼1.7:1 ratio, 90 mg, 0.346 mmol, 1 equiv)

and second-generation Grubbs catalyst (11.7 mg, 0.0138 mmol,

0.04 equiv) in CH₂Cl₂(4 mL) for 3 h aﬀorded after column chro-

matography (10% and 30% CH₂Cl₂in hexanes) 42.9 mg (53%) of

(−)-1a ([α]_D= −93.3 (c = 1.28, CHCl₃, ee not determined)) and

25 mg (31%) of (+)-2a ([α]_D= +66.2 (c = 0.72, CHCl₃, 76% ee)) as

colorless oils. The enantiomeric excess of (+)-2a was determined by

HPLC (OJ column, hexanes, 0.4 mL/min, 10 °C, t_R(minor) = 14.9 min,

t_R(major) = 17.6 min). The enantiomeric excess of (−)-1a could not be

obtained by HPLC but was inferred to be 76% ee on the basis of that of

(+)-2a.

Wittig Rearrangements of (−)-1a and (+)-2a. Preparation of

(−)-3a and (+)-4a from (−)-1a. Applying general procedure H to

(−)-1a (ca. 76% ee, 42.9 mg, 0.1846 mmol, 1 equiv) and n-butyllithium

(1.6 M in hexanes, 0.17 mL, 1.5 equiv) in THF (2.3 mL) at −78 °C for

5 min aﬀorded after workup and column chromatography (5% and 10%

EtOAc in hexanes) 24.1 mg (56%) of (−)-3a (dr = 20:1) in 62% ee

([α]_D= −25.6 (c = 0.83, CHCl₃)) and 9.6 mg (22%) of (+)-4a (dr >

20:1) in 73% ee ([α]_D= +73.4 (c = 0.96, CHCl₃)). Chiral HPLC

conditions for (−)-3a: OJ column, hexanes, 0.7 mL/min, 20 °C,

t_R(major) = 12.7 min, t_R(minor) = 25.8 min. Chiral HPLC conditions

for (+)-4a: OJ column, 0.5% i-PrOH/hexanes, 0.4 mL/min, 20 °C,

t_R(minor) = 22.8 min, t_R(major) = 25.0 min.

(−)-(1R,2R)-5⁸³⁻⁸⁶as a colorless oil: H NMR (500 MHz, CDCl₃)

1

δ 9.30 (d, J = 5.0 Hz, 1 H), 7.28 (m, 2 H), 7.21 (m, 1 H), 7.08 (m,

2 H), 2.61 (m, 1 H), 2.16 (m, 1 H), 1.17 (dt, J = 5.5, 10.0 Hz, 1 H),

1.52 (ddd, J = 5.0, 7.0, 8.5 Hz, 1 H); [α]_D= −183.4 (c = 0.46, CHCl₃)

(lit.^83,84[α]_D= −378 (c = 0.374, CHCl₃)).

Preparation of Compound (−)-6. To a solution of (+)-4a (72% ee,

15 mg, 0.065 mmol) in EtOAc (1 mL) was added 10% Pd/C (∼3 mg)

(Scheme 15). The system was closed with a septum, evacuated, and

Scheme 15. Determination of the Absolute Stereochemistry

of Compound (+)-4a

Preparation of (+)-3a and (−)-4a from (+)-2a. Applying general

procedure H to (+)-2a (76% ee, 25 mg, 0.1076 mmol, 1 equiv) and

sec-butyllithium (1.4 M in cyclohexane, 0.23 mL, 3 equiv) in THF

(1.4 mL) at −78 °C for 3 h aﬀorded after workup and column

chromatography (5% and 10% EtOAc in hexanes) 15 mg (56%) of

(+)-3a (dr = 20:1) in 56% ee ([α]_D= +27 (c = 0.79, CHCl₃)) and

5.2 mg (21%) of (−)-4a (dr > 20:1) in 74% ee ([α]_D= −52.7 (c =

0.48, CHCl₃)).

ﬁlled with H₂. A H₂balloon was attached and the mixture vigorously

stirred for 30 min. Then the reaction mixture was ﬁltered though a

short plug of silica and concentrated. Column chromatography

(HPLC conditions: OJ column, 0.5% i-PrOH/hexanes, 0.4 mL/min,

Assignment of Relative and Absolutive Stereochemistries of

Precursors S3, Cyclic Ethers, and Wittig Rearrangement

Products. The relative stereochemistries of cyclic ethers 1 (trans)

and 2 (cis) were assigned by comparison with the ¹H NMR spectra of

compounds 1a and 2a, whose relative stereochemistries have been

determined by NOE studies. The relative stereochemistries of pre-

cursors S3 (syn/anti) were assigned on the basis of the assignment of

the corresponding cyclic ethers 1 and 2. The relative and absolute

stereochemistries of [1,4]-Wittig product (−)-3a were assigned by

derivatization to the known aldehyde (−)-5a. The relative and

absolute stereochemistries of [1,2]-Wittig product (+)-4a were

determined by X-ray crystallographic analysis of its 3,5-dinitrobenzoate

derivative (−)-7. The relative stereochemistries of all other [1,4]- and

20 °C) aﬀorded 15 mg (100%) of (−)-6 as a colorless oil: [α]_D

=

1

−13.5° (c = 1, CHCl₃, 72% ee); H NMR (500 MHz, CDCl₃) δ 7.24

(m, 2 H), 7.17 (m, 3 H), 3.20 (dd, J = 5.0, 8.0 Hz, 1 H), 2.36 (m, 1

H), 2.05 (m, 2 H), 1.92 (m, 2 H), 1.72 (m, 1 H), −0.31 (s, 9 H); ¹³C

NMR (151 MHz, CDCl₃) δ 143.7, 128.4 (2 C), 128.2 (2 C), 126.4,

80.1, 57.9, 36.1, 31.1, 22.5, −3.2; IR (ﬁlm) 3430, 2951 cm⁻¹; HRMS

(ESI) m/z 217.1413 [(M − OH)⁺, calcd for C₁₄H₂₁Si, 217.1404].

Preparation of Compound (−)-(1S,2S)-7. To a solution of (−)-6

(15 mg, 0.064 mmol, 1 equiv) in pyridine (2 mL) was added 3,5-

dinitrobenzoyl chloride (74.5 mg, 0.323 mmol, 5 equiv), and the

mixture was vigorously stirred for ∼36 h. The reaction was quenched

with water (2 mL) and diluted with diethyl ether. The aqueous phase

was extracted with diethyl ether (3 × 3 mL). Combined organic

extracts were washed with 0.1 M HCl (2 mL) and brine, dried over

MgSO₄, and concentrated. Column chromatography (4% EtOAc in

hexanes) followed by recrystallization from hexanes/CH₂Cl₂aﬀorded

10.6 mg (39%) of (−)-7 as white crystals suitable for X-ray analysis

and 4.4 mg (29%) of unreacted alcohol. The absolute stereochemistry

was determined as 1S,2S. Characterization data for (−)-(1S,2S)-7:

[α]_D= −87 (c = 1.06, CHCl₃); mp 137 °C dec; ¹H NMR (500 MHz,

CDCl₃) δ 9.21 (t, J = 2.0 Hz, 1 H), 9.10 (d, J = 2.0 Hz, 1 H), 7.32−

7.22 (m, 5 H), 4.05 (dd, J = 5.5, 7.0 Hz, 1 H), 2.35 (m, 1 H), 2.29−

2.19 (m, 2 H), 2.18−2.09 (m, 2 H), 1.93 (m, 1 H), −0.19. ¹³C NMR

(126 MHz, CDCl₃) δ 162.2, 148.7, 142.2, 135.2, 129.2, 129.1, 128.3,

127.1, 122.1, 96.2, 53.4, 35.5, 32.1, 23.7, −0.8; IR (ﬁlm) 3029, 2955,

1720, 1625, 910 cm⁻¹; HRMS (EI) m/z 428.1404 [(M)⁺, calcd for

C₂₁H₂₄N₂O₆Si, 428.1404].

1

[1,2]-Wittig products were assigned by comparison of their H NMR

spectra with those of compounds 3a and 4a, respectively. Further

support for the relative stereochemistries of [1,2]-Wittig products was

obtained by X-ray crystallographic analysis of compound 4s.

Preparation of Compound (−)-5. Compound (−)-3a was

derivatized to the known aldehyde (−)-5 (Scheme 14).⁸³⁻⁸⁶Enolate

Scheme 14. Determination of the Absolute Stereochemistry

of Compound (−)-3a

formation/benzoylation: To a solution of freshly distilled diisopropyl-

amine (41 μL, 0.29 mmol, 1.3 equiv) in THF (1 mL) at −78 °C was

added n-butyllithium (1.6 M in hexanes, 0.17 mL, 0.266 mmol,

1.2 equiv) slowly. After 10 min the reaction was warmed to 0 °C for

15 min and cooled to −78 °C. Compound (−)-3a (62% ee, 51.5 mg,

Deuterium-Trapping Experiments. Preparation of Com-

pounds d-2d, d₂-1d, d-3d, d₂-8, and d-9. Applying general procedure

H to 2d (96 mg, 0.366 mmol, 1 equiv) and sec-butyllithium (1.4 M in

Z

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Scheme 16. Competitive ortho Metalation vs Allylic Deprotonation of Compound 2d

hexanes, 0.78 mL, 3 equiv) in THF (4 mL) at −78 °C for 6 h aﬀorded

after quenching with D₂O (1 mL), regular workup, and column

chromatography (30% CH₂Cl₂in hexanes, then 5% and 10% EtOAc in

hexanes) 25.2 mg (26%) of d-2d, 2.2 mg (2%) of d₂-1d, 28 mg (30%)

of d-3d, 6.9 mg (7%) of d₂-8, and 13.2 mg (19%) of d-9 (dr > 20:1) as

colorless oils (Scheme 16). Spectroscopic data for d₂-8: ¹H NMR (500

MHz, CDCl₃) δ 7.25 (m, 2 H), 6.87 (m, 1 H), 5.02 (m, 1 H), 4.70

(dd, J = 2.5, 10.0 Hz, 1 H), 3.79 (s, 3 H), 2.18 (m, 1 H), 2.00 (dddd, J

= 1.0, 2.5, 6.5, 13.5, Hz, 1 H), 1.80 (dt, J = 10.0, 13.0 Hz, 1 H), −0.10

(s, 9 H); ¹³C NMR (126 MHz, CDCl₃) δ 160.4, 135.5, 126.9 (2 C),

126.8 (2 C), 113.6, 109.7, 75.8, 55.3, 30.2, 20.9 (t, J = 20.2 Hz), −2.4.

Spectroscopic data for d-9: ¹H NMR (500 MHz, CDCl₃) δ 9.82 (t, J =

2.0 Hz, 1 H), 7.01 (m, 2 H), 6.79 (d, J = 9.0 Hz, ∼1 H), 3.76 (s, 3 H),

2.50 (ddd, A of ABX system, J = 2.0, 7.0, 17.5 Hz, 1 H), 2.43 (ddd, B

of ABX system, J = 2.0, 7.5, 17.5 Hz, 1 H), 1.71 (dt, J = 5.0, 9.0 Hz, 1

H), 1.23 (m, 1 H), 0.98 (dt, J = 5.5, 8.5 Hz, 1 H), 0.80 (dt, J = 5.0, 8.5

Hz, 1 H); ¹³C NMR (126 MHz, CDCl₃) δ 201.7, 157.8, 127.1, 127.0,

113.9, 55.3, 48.2, 21.9, 15.5, 14.6.

Observation of Compounds d-2aa, d-3aa, and Enolic 3aa.

Applying general procedure H to 2aa (16.8 mg, 0.07 mmol, 1 equiv)

and sec-butyllithium (1.4 M in hexanes, 0.15 mL, 3 equiv) in THF

(0.9 mL) at −78 °C for 3 h and quenching with D₂O aﬀorded

following regular workup a mixture of d-2aa (dr > 20:1), d-3aa (dr ≈

1.7:1), and enolic 3aa (dr not determined) in a 0.36:2.7:2.3 ratio, as

1

determined from the crude mixture by H NMR (Scheme 18).

Scheme 18. Competitive Thiophene Metalation vs Allylic

Deprotonation of 2aa

Preparation of Compounds d-2h, d₂-1h, and d₂-10. Applying

general procedure H to 2h (52.9 mg, 0.211 mmol, 1 equiv) and sec-

butyllithium (1.4 M in hexanes, 0.45 mL, 3 equiv) in THF (2.6 mL) at

−78 °C for 0.5 h aﬀorded after quenching with D₂O (1 mL), regular

workup, and column chromatography (3% EtOAc in hexanes) 22.7 mg

(43%) of d-2h, 10 mg (19%) of d₂-1h, and 7.9 mg (15%) of d₂-10 as

Observation of Compounds d-2bb and d-3bb. Applying general

procedure H to 2bb (9.8 mg, 0.044 mmol, 1 equiv) and sec-butyllithium

(1.4 M in hexanes, 94 μL, 3 equiv) in THF (0.6 mL) at −78 °C for 1 h

and quenching with D₂O aﬀorded following regular workup mostly

d-2bb (dr > 20:1) and traces of d-3aa (dr not determined), as deter-

1

colorless oils (Scheme 17). Spectroscopic data for d₂-10: H NMR

Scheme 17. Competitive ortho Metalation vs Allylic

Deprotonation of 2h

1

mined from the crude mixture by H NMR (Scheme 19). Complete

Scheme 19. Competitive Furan Metallation vs Allylic

Deprotonation of 2bb

deuterium incorporation at the 5-position of the furyl group in d-2bb is

observed. Deuterium incorporation into d-3aa was not determined due

to overlap with other signals.

Trapping of Intermediate Allylic Anion (Species A in Scheme 10).

Following general procedure H, to 1a (73 mg, 0.314 mmol, 1 equiv) in

THF (4 mL) was added n-butyllithium (1.4 M in hexanes, 0.78 mL,

3 equiv) quickly at −78 °C, and immediately (<1 s) D₂O was added

quickly via syringe. After regular workup the crude reaction was

(500 MHz, CDCl₃) δ 7.31 (m, 2 H), 7.03 (m, 1 H), 5.06 (m, 1 H),

4.75 (dd, J = 2.5, 10.0 Hz, 1 H), 2.20 (m, 1 H), 2.03 (m, 1 H), 1.81

(dt, J = 10.0, 13.5 Hz, 1 H), 0.13 (s, 9 H).

AA

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The Journal of Organic Chemistry

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1

analyzed by H NMR. Compounds d-1a, enolic 3aa, 4a, and 11 were

was supported by the Harold Hart Endowed Fellowship. We

thank Dr. Richard Staples for crystallographic analysis.

present in a 1.0:0.33:0.17:0.11 ratio.

Control Experiments To Discard [1,2]/[1,4]-Interconversion.

Evidence for Keto−Enol Equilibration of (Cyclopropyl)acyl-

silanes. In the early stage of this study involving the rearrangement

of diastereomers 1a and 2a, we were unable to obtain reproducible

isolated yields of both [1,4] (3a) and [1,2] (4a) products. The ratios

of 3a and 4a in the crude ¹H NMR varied in each experiment, and the

determination of the diastereomeric ratio of 3a was complicated by the

presence of additional signals in the cyclopropyl region (1.8−0.6 ppm).

In addition, the integration of these signals correlated well with a

doublet around 4.52 ppm (J = 7.5 Hz) and a singlet around 4.35 ppm.

We later found that subjecting the reaction mixture to column chro-

matography immediately after workup (avoiding additional manipu-

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* Supporting Information

Optimization results, X-ray crystallographic data, ¹H NMR and

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*E-mail: maleczka@chemistry.msu.edu.

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We thank the National Institutes of Health (Grant HL-58114),

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AC

DOI: 10.1021/jo5026942

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Stereoconvergent [1,2]- and [1,4]-wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans: A tale of steric Vs electronic regiocontrol of divergent pathways

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