Asymmetric synthesis of cyclic β-hydroxyallylsilanes via sequential allyltitanation-ring closing metathesis

Tetrahedron 60 (2004) 7325–7344

Asymmetric synthesis of cyclic b-hydroxyallylsilanes via

sequential allyltitanation-ring closing metathesis

a

Jean-Michel Adam, Laurence de Fays, Michel Laguerre and Leon Ghosez

b

,

*

´

a

´ ´

Departement de Chimie, Universite catholique de Louvain, place L. Pasteur, B-1348 Louvain-la-Neuve, Belgium

´

Institut Europeen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France

b

Received 6 April 2004; revised 19 May 2004; accepted 21 May 2004

Available online 26 June 2004

Dedicated to Professor Robert H. Grubbs for his seminal contributions to organic and polymer synthesis

Abstract—Highly enantioenriched cyclic b-hydroxyallylsilanes have been prepared via enantioselective allylation of unsaturated aldehydes

using a chiral allyltitanium reagent, followed by a ring-closing metathesis. Functionalized rings of various sizes have been synthesized and

the electronic effect of the silicon group in the RCM reaction has been studied. The resulting cyclic b-hydroxyallylsilanes reacted

stereoselectively with a variety of electrophilic reagents. A ﬁrst application of this method to the synthesis of a highly functionalized

dihydropyrane is reported.

1. Introduction

intramolecular cycloaddition reaction of the allylsilane to

an in situ generated keteniminium reagent. This led to

bicyclo[3.2.0]heptan-6-one 1 in good yield and high

enantiomeric excess.

A convergent strategy for the enantioselective synthesis of

(poly)cyclic molecules consists of a two-step sequence of

reactions starting with an asymmetric allylation of an

aldehyde with an organometallic reagent followed by

an intramolecular diastereoselective silicon-directed

(cyclo)addition reaction (Scheme 1).

Scheme 1.

A ﬁrst example of this strategy has been reported in 1999 by

our group.¹It involved the reaction of a silyl-substituted

allyltitanate reagent with an aldehyde carrying a tertiary

amide group at the b-carbon followed by a silicon-directed

Scheme 2.

The combination of step 1 with a ring-closing metathesis

(RCM)²was considered as an attractive sequence for the

synthesis of b-hydroxyallylsilanes 2 which can be looked

upon as chiral equivalents of cyclic conjugated dienes

(Scheme 2). The dense functionality of these intermediates

should allow to take full beneﬁt of the presence of a silyl

Keywords: Ring closing metathesis; Allyltitanation; b-Hydroxy-allylsilane;

Asymmetric synthesis; Dihydropyran.

*

Corresponding author. Tel.: þ33-5-4000-2217; fax: þ33-5-4000-2222;

e-mail address: l.ghosez@iecb.u-bordeaux.fr

doi:10.1016/j.tet.2004.05.058

7326

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

substituent as control element for further transformations

into a variety of enantiopure mono- and polycyclic

compounds. In earlier examples of sequential asymmetric

allylation-RCM, the oleﬁnic partners for the RCM were

always linked by a heteroatom which became part of the

newly formed ring.³A preliminary report on the sequence of

Scheme 2 has been recently published by Roush et al. who

elegantly applied it to the synthesis of conduritols and

inositols of high enantiomeric purities.⁴We now wish to

report our studies of the scope and limitation of the

allylation-RCM sequence and illustrate the synthetic

potential of the resulting products 2.⁵

methylidene carbene was formed. We selected hexene as a

reference, 4-methylpentene to evaluate the impact of steric

hindrance, and allyldimethylphenylsilane to measure the

inﬂuence of the silyl substituent.

Examination of k₁rel showed that electronic effects

mediated by s-bonds did not strongly inﬂuence the

reactivity of the oleﬁns. The lower rate observed for the

allylsilane was mainly attributed to steric effects since

the silicon b-effect should have increased the rate of

reaction with the electrophilic carbene complex. The trend

in reactivity (k₂rel) seems to roughly follow the steric

demand of the substituents. The more reactive complex was

the allyldimethylphenylsilane-substituted carbene. This

could be explained by an increase of phosphine lability as

a result of the presence of the bulky silyl group (Scheme 3).⁹

2. Substrate design

2.1. Carbene-exchange reaction

The inﬂuence of the silyl group on other parameters such as

oleﬁn complexation (step 1) or the rate of the metathesis

(step 2) was believed to be limited. First, the geometric

requirement for a strong hyperconjugating interaction

would be difﬁcult to fulﬁll and secondly, electronic effects

are only slightly inﬂuencing step 2 as seen by the small r

value determined in the gas phase (0.69).⁸Moreover, if

operating, the b-effect is expected to disfavour oleﬁn

complexation which should result in a decrease of

reactivity. We thus propose that, in carbene exchange

reactions, the silicon b-effect is not an important parameter

and that steric effects are probably the true reactivity

modulators.

In the sequence described in Scheme 2, one of the oleﬁnic

partners for the RCM is an allysilane. In order to optimize

the reaction in terms of yields and turnover of the catalyst,

we decided to perform some model experiments.

Several examples of RCM of allylsilanes have been

reported. Crowe and coworkers assigned the preference of

allylsilanes for cross-metathesis to the silicon b-effect.⁶

Doubts about the role of this b-effect arose from a report of

Blechert et al.⁷Based on a competition experiment between

TMS–CH₂CHvCH₂and t-Bu–CH₂CHvCH₂, they

deduced that the b-effect of silicon did not signiﬁcantly

affect the rate of metathesis. However, since the kinetics of

the reaction were not known, the identiﬁcation of the

carbene from which the cross-metathesis mainly occurred

was not possible.

We ﬁrst evaluated the carbene exchange reaction between

several oleﬁns and Grubbs’ catalyst 3 (Table 1). It was

possible to determine K and hence k₂by taking advantage of

the higher rate of the carbene exchange reaction as

compared to the productive metathesis.⁸Indeed, equi-

librium was reached before a signiﬁcant amount of

Scheme 3.

2.2. RCM model experiments

Table 1. Relative second-order rate constants (krel) for metathesis reactions

using 10 equiv. of oleﬁn

2.2.1. Synthesis of the model substrates. Two types of

model substrates were prepared to study the reactivity of the

allylsilane. Racemic substrates 4rac and 5rac were prepared

by allylmetallations of hept-4-enal. Acetylation of 5rac

gave 6rac (Scheme 4).

Oleﬁn

k₁rel^a

0.5

K^b

k₂rel^a

4.8

3.1^0.2£10²³

19^3£10^22c

0.9

1.6

Scheme 4. Reagents and conditions: (a) allylmagnesium bromide

(1.1 equiv.), Et₂O, 95%; (b) allyldimethylphenylsilane (1.15 equiv.),

THF, n-BuLi (1.15 equiv.), 3 h, 278 8C then 40% aqueous NH₄F, 15 h,

rt, 87%; (c) pyridine (4 equiv.), CH₃COCl (3 equiv.), CH₂Cl₂, 1.5 h, rt,

95%.

1

32^4£10²²

1

a

k₁rel¼k₁(oleﬁn)/k₁(hexene), k₂rel¼k₂(oleﬁn)/k₂(hexene).

k(K)^standard deviation.

b

c

Racemic dienes 7rac-9rac were prepared by allyltitanation

of 4-pentenal followed by protection of the alcohol by either

an acetyl or a t-butyldimethylsilyl group (Scheme 5).

The equilibrium constant (K¼0.32, rt) for hexene is slightly higher than

the previously reported value of 0.2 determined by Grubbs and coworkers

for the same reaction at 7 8C.⁸

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7327

active and decompose more slowly than the corresponding

methylidene.¹²

We checked that the initiation was taking place at the

terminal oleﬁn. Diene 5rac was reacted with 0.8 equiv. of 3

in reﬂuxing CH₂Cl₂and the crude mixture was analysed by

GC-MS (EI and CI). In addition to the starting material and

the cyclized product, analyses revealed the presence of

tricyclohexylphosphine, styrene, stilbene as well as only

trace amounts of 2-ethylstyrene (Scheme 8).

Scheme 5. Reagents and conditions: (a) allyldimethylphenylsilane

(1.15 equiv.), nBuLi 2.1 M (1.15 equiv.), ClTi(OiPr)₃(1.25 equiv.) to

give g-silylallyltitanate, then 4-pentenal, THF, 278 8C, 2 h, 75%;

(b) TBSCl (1.2 equiv.), imidazole (1.3 equiv.), 36 h, 50 8C, DMF, 83%;

(c) pyridine (4 equiv.), CH₃COCl (3 equiv.), CH₂Cl₂, 30 min, rt, 95%.

Diene 10rac, bearing a cyclohexyl group at the allylic

position was prepared by a simple sequence starting from

cyclohexylcarboxaldehyde (Scheme 6). This diene gave us

the opportunity to evaluate the accelerating effect due to

steric hindrance. The cyclohexyl group was selected since it

has an A value comparable to that of a TMS group and will

induce no electronic effect.¹⁰Wittig oleﬁnation, reduction

of the ester, Corey bromination of the allylic alcohol and

chromium-mediated allylation¹¹of pentenal gave the

desired homoallylic alcohol 11rac. Protection of the alcohol

by a TBS group yielded 10rac.

Scheme 8.

The homoallylic alkoxy derivatives 4rac-6rac were reacted

1

with a catalytic amount of 3. H NMR and GC analysis of

the crude mixtures indicated clean conversions. Table 2

shows that the main inﬂuence of the silicon group is to

decrease the rate of the RCM due to its steric hindrance.

Table 2.

Diene R¼

R⁰¼

3

(mol%)

Temperature Time Product Yield

(%)

Scheme 6. Reagents and conditions: (a) CHCl₃, reﬂux, 87%, 97% of E

(GC/NMR); (b) DIBAL, .99%.; (c) DMS/NBS, 78%; (d) CrCl₂(2 equiv.),

THF, rt, 15 h, 61–71%; (e) TBSCl (1.1 equiv), imidazole (2 equiv), 16 h,

50 8C, DMF, 73%.

4rac

5rac

H

1.6

rt

1 h 12rac

,5 min 12rac

.95

86

Reﬂux

PhMe₂Si 3.2

42 h

24 h

13rac

14rac

6rac Ac PhMe₂Si 1.6

91

2.2.2. Ring closing metathesis. We ﬁrst examined dienes

4rac-6rac. In this case, we expected the initiation to take

place mainly at the allylsilane double bond since the other

oleﬁn is sterically protected (Scheme 7).

The modiﬁcation of the initiation site should lead to an

increase of reactivity: when the two double bonds are

terminal, the carbene complex will react faster at the less

hindered double bond, the one without any substituent at the

allylic position (Scheme 9).

Scheme 7.

Scheme 9.

On the basis of the results of Section 2.1, we hoped that

these carbenes would also be more reactive in the

productive metathesis step as a result of increased

phosphine lability of the silyl-substituted carbene. In the

case described in Scheme 7 the propagating species would

be an alkylidene carbene which has been shown to be more

The three dienes 7rac-9rac were reacted with catalyst 3

with varying efﬁciency depending on the protecting group

(Table 3). With 1.6 mol% of catalyst at room temperature,

the homoallylic alcohol 7rac reacted rapidly up to 40%

conversion at which point the reaction nearly stopped (entry

7328

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

Table 3.

GC analysis of the mixture after 20 s, 40 s and 9 min

showed no signiﬁcant difference in reactivity between the

two dienes. This was also conﬁrmed in separate experi-

ments. Thus the enhanced reactivity of these dienes is

primarily a consequence of the bulk of the substituents

which could accelerate the loss of a phosphine ligand but

probably also increase the population of the conformation

necessary for RCM.

Entry Diene R¼

3

(mol%)

Temperature Time Product Conv.

(%)

1

2

3

4

5

6

7rac

8rac

9rac

H

1.6

4.8

1.6

rt

3 h^a

1.5 h

2 h

13rac

49

64

98

. 99

98

3. Asymmetric allylation-RCM: application to the

synthesis of b-hydroxyallylsilanes

Reﬂux

rt

Reﬂux

H

Ac

TBS 1.6

TBS 0.05

20 min 14rac

15rac

2 min

1 h

3.1. Preparation of chiral diene equivalents via

asymmetric allyltitanation

a

40% conversion after 5 min then, the reaction nearly stopped.

Unlike Roush et al., we performed the asymmetric

allylmetallation of the unsaturated aldehydes 17a-e¹⁴with

(E)-g-dimethylphenylsilyl substituted titanium reagent 18

generated from allyldimethylphenylsilane, n-BuLi and

(R,R)-Cl–TiCpTADDOL at 278 8C (Table 4). These

allylmetal reagents were known to give the anti-b-

hydroxyallylsilanes in good yields and high enantiomeric

purities.¹⁵This was also the case here. The absolute

conﬁgurations of 19a-e were assigned by analogy with

previous results.¹As will be shown later, this was conﬁrmed

by analysis of the absolute conformation of the triol derived

from 19b (see Scheme 17).

1). Heating at reﬂux didn’t allow complete conversion

(entry 2). It was necessary to triple the catalyst concen-

tration to achieve a complete conversion of the starting

material (entry 3). The acetyl-protected diene 8rac gave a

92% conversion after only 4 min and quantitative conver-

sion after 20 min at room temperature (entry 4). More

surprising was the fast RCM of the t-butyldimethylsilyl

ether 9rac, the reaction being complete within 2 min at

room temperature (entry 5). In this case, it was possible to

complete the RCM in 1 h in reﬂuxing dichloromethane with

as little as 0.05 mol% catalyst (entry 6).

Interestingly, comparison of Table 2 (entry 1) and Table 3

(entry 1) with a previous result on metathesis of hept-1,6-

diene-4-ol¹³(Scheme 10) indicates that proper choice of the

site of carbene exchange could prevent formation of

unreactive chelates and hence deliver higher possible

turnover.

Table 4. Asymmetric allylmetallation of terminally unsaturated aldehydes

17a-e with 18

Scheme 10.

The unexpected high reactivity of diene 9rac could result

from the high nucleophilicity of the allylsilane as proposed

by Crowe and coworkers.⁶If the silicon b-effect was

responsible for this high reactivity, the replacement of the

silyl substituent by a group of comparable steric hindrance

but lacking electronic effects such as cyclohexyl, should

induce a decrease in reactivity. A competition experiment

was performed using equimolar amounts of 9rac and 10rac

(Scheme 11).

Entry

Aldehyde

n¼

Product

Yield (%)

ee (%)

1

2

3

4

5

17a

17b

17c

17d

17e

1

2

3

4

8

19a

19b

19c

19d

19e

68

75

67

71

96

92

90

94

91

Reagents and conditions: (a) n-BuLi (1.1 equiv.) in THF, 20 min, rt then

(R,R)-Cl–TiCpTADDOL (1.15 equiv.), 30 min, 278 8C to give a solution

of 18; (b) aldehyde 17a-e (1 equiv.), 3 h, 278 8C, 40% aqueous NH₄F,

15 h, rt, ﬂash chromatography, ee determined by HPLC on a Chiralcel AS

or OD column, the other diastereoisomer was not detected (de . 98%).

Scheme 12. Reagents and conditions: (a) pyridine (3.5 equiv.), CH₃COCl

(2.5 equiv.), CH₂Cl₂, 30 min, rt; (b) TBSCl (1.5 equiv.), imidazole

(4 equiv.), 16 h, 50 8C, DMF.

Scheme 11.

Table 5. Ring-closing metathesis of dienes 19b, 20 and 21: assays with different metathesis pre-catalysts and alcohol protecting groups

Entry

Substrate

Catalyst

(mol%)

Solvent

Temperature

t

Product

Yield (%)

1

19b

21a

3

5

CH₂Cl₂

Reﬂux

2 h

13

13 (87%)

2

3

2

CH₂Cl₂

rt

5 min

22a

22a (98%)

22b (98%)

21b

20c

1.6

22b

24

4

5

3

6

CH₂Cl₂

Toluene

rt

48 h

24 h

24 (0%)

7.5

60 8C

24 (66%)^a

6

7

8

9

21c

21d

3

20

7.5

2

CH₂Cl₂

Toluene

CH₂Cl₂

rt

4 h

2 h

22c

22c (70%)

22c (93%)

3

23

60 8C

rt

22c (76%)þ22b (20%)

2

22c (82%)þ22b (6%)

10

11

12

13

14

3

30

20

7.5

20

Benzene-d₆

CH₂Cl₂

Toluene

CDCl₃

60 8C

rt

60 8C

rt

24 h

72 h

11 h

1 h

22d

25

—

23

3

22c (54%)^aþ21d (42%)^a

22c (89%)^aþ22d (8%)^a

22c (42%)^aþ22d (52%)^a

25 (42%)^aþ21d (51%)^a

CH₂Cl₂

72 h

15

20e

21e

3

20

CH₂Cl₂

Toluene

rt

72 h

48 h

No RCM product

—

16

60 8C

a

Observed conversion by GC-MS, not isolated yield.

7330

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

Acetylation or silylation of the alcohols 19a-e yielded

the corresponding esters 20c,e or silyl ethers 21a-e

(Scheme 12).

Indeed, a mixture of the terminal 21d and isomerized oleﬁn

25 was formed when 21d was exposed to Grubbs catalyst at

room temperature for 72 h (entry 14). This type of

isomerization is often encountered in RCM involving

weakly reactive systems.¹⁷

3.2. Ring-closing metathesis

RCM of the unprotected alcohol 19b using Grubbs’ catalyst

3 (5 mol%) gave the cyclohexenylsilane 13 in good yield

(Table 5, entry 1). t-Butyldimethylsilyl ethers 21a-b under-

went an extremely fast RCM reaction in the presence of

catalyst 3 (entries 2 and 3). Compounds 22a-b were

obtained in excellent yields and the same enantiomeric

purities as the starting dienes. As it could be expected, the

formation of the 7-membered ring proved to be more

difﬁcult: the RCM of diene 21c was much slower, requiring

higher temperatures and more catalyst (entries 6 and 7). The

use of 2 mol% of the 2nd generation Grubbs’ catalyst 23¹⁶

enabled the reaction to take place at room temperature in 2 h

(entry 9). However, traces of the 6-membered ring were

observed in presence of catalyst 23. The proportion of 22b

increased when the reaction was conducted in toluene at

60 8C (entry 8). RCM of the acetate 20c was slower. Heating

the dienes at 60 8C in toluene in the presence of 7.5 mol% of

3 gave 66% yield of 24 (entry 5).

We reasoned that we might avoid oleﬁn isomerization if we

could force the catalyst to enter at the allylsilane position.

The introduction of an ethyl substituent at the terminal

carbon atom of the oleﬁn was expected to slow down

carbene formation at that double bond (Scheme 14).

Scheme 14.

Diene 26 was synthesized by the allytitanation-metathesis

sequence and subjected to RCM conditions (Table 6).

Unfortunately, at room temperature neither 3 nor 23 were

efﬁcient enough to promote the formation of the

8-membered ring (entries 1 and 2). When the reaction was

carried out in toluene at 60 8C, no reaction occured in

presence of catalyst 3 (entry 3). With catalyst 23

isomerization preceded RCM, giving again the 7-membered

ring 22c (entry 4).

The treatment of 20e and 21e with 3 didn’t give the

12-membered ring (entries 15 and 16). Close NMR

observation after adding 1 equiv. of catalyst showed

complete conversion of the less hindered terminal

oleﬁn into the corresponding ruthenium–carbene complex

but no cyclization occurred even after 2 days at 60 8C in

toluene. The catalyst 23 didn’t give any metathesis product

neither.

Table 6. RCM of 26

A ﬁrst attempt to form the 8-membered ring was conducted

in boiling deuterated benzene and followed by NMR. Again,

the only product was the ruthenium–carbene complex

(entry 10). The use of the more reactive catalyst 23 did not

give the 8-membered ring. Instead a mixture of the

7-membered ring 22c and starting diene 21c was obtained

when the reaction was run at room temperature (entry 11).

At 608 in toluene (entry 12), the conversion was complete,

but gave only a small amount of the 8-membered ring 22d,

the main product being the 7-membered ring 22c. Surpris-

ingly, in deuterated chloroform at 60 8C, the major product

was 22d as shown by GC-MS analysis (entry 13).

Unfortunately this product could not be separated from

the lower homologue 22c. These results can be explained by

a ruthenium-catalyzed isomerization of diene 21d into the

more stable internal oleﬁn 25 (Scheme 13).

Entry

Catalyst

Conditions

Result

1

2

3

4

3

23

3

CH₂Cl₂, rt, 2 d

Toluene, 60 8C

No reaction

22c 62%þ22d 12%

23

Reagents and conditions: (a) n-BuLi (1.1 equiv.) in THF, 20 min, rt then

(R,R)-Cl–TiCpTADDOL (1.15 equiv.), 30 min, 278 8C then cis-6-nonenal

(1 equiv.), 3 h, 278 8C, 40% aqueous NH₄F, 15 h, rt, 64%; (b) TBSCl

(1.1 equiv.), imidazole (2 equiv.), 16 h, 50 8C, DMF, 63%.

Clearly the synthetic utility of this asymmetric allylmetalla-

tion-RCM sequence would be greatly enhanced if it could

be successfully applied to substituted aldehydes

(Scheme 15). We have therefore examined the allyltitana-

tion of the acetonide-protected aldehyde 27¹⁸which

proceeded indeed with high diastereoselectivity to give

the corresponding anti-b-hydroxyallylsilane 28. The corre-

sponding acetate 29 was subjected to RCM in the presence

of catalyst 23 to give 80% yield of cyclohexene 30 in high

enantiomeric purity (ee .98%, d.r.: 13:1 determined by

chiral HPLC).

3.3. Conformations of the cyclic cis-b-hydroxyallyl-

silanes

Scheme 13.

The conformations of the cyclic cis-b-hydroxyallylsilanes

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7331

¹H NMR analysis and molecular modeling⁵of 30 also

suggested a half-chair conformation with a pseudoaxial silyl

substituent.

4. Transformations of cyclic b-hydroxyallylsilanes

Compounds 13 and 22a-c contain a combination of an allyl-

and a b-silyloxy-silane which should be prone to undergo

interesting transformations leading to a wide variety of

enantioenriched, highly functionalized building blocks.

Scheme 16 shows an illustrative selection of diastereo-

selective transformations of 22a-c. In all cases, the axial

silyl group acts as an efﬁcient stereodirecting group,

favouring the attack on the opposite face. HPLC analyses

showed that the enantiomeric purity of the starting materials

was conserved after the transformations.

Scheme 15. Reagents and conditions: (a) n-BuLi (1.1 equiv.) in THF,

20 min, rt then (R,R)-Cl–TiCpTADDOL (1.15 equiv.), 30 min, 278 8C

then 27 (1 equiv.), 3 h, 278 8C, 40% aqueous NH₄F, 15 h, rt, 55%;

(b) pyridine (3.5 equiv.), CH₃COCl (2.5 equiv.), CH₂Cl₂, 4 h, rt, 89%;

(c) catalyst 23 (8 mol%), boiling CH₂Cl₂, 2 h, 80%.

The cyclohexenylsilanes 13 and 22a,c were ﬁrst reacted

with dichlorocarbene and the relative conﬁguration of the

cycloadducts was ascertained by ¹H NOE experiments. The

facial selectivity was excellent for 22a and 13 (only the exo

isomer was detected by HPLC) but a 10:1 mixture of exo

and endo was obtained in the case of 33. The addition of

ethyldiazoacetate in presence of [Rh(OAc)₂]₂yielded 43%

of 34 in a 3:1 mixture of epimers but with complete facial

selectivity. The use of Cu(acac)₂instead, as described by

Landais et al., gave the cyclopropane with a better yield

22a-c were examined by correlation of the experimental

coupling constants with calculated values obtained by a

Monte–Carlo conformational search (Fig. 1). The experi-

mental coupling constants of the ring-protons were

compared with the one calculated for the representative

structures of each cluster obtained from the conformational

search. The existence of second-order effects and long range

couplings speciﬁc to an allylic system led us to use an

iterative procedure to assign all coupling constants values.

In all three cases the values of the coupling constants

conﬁrmed that the silicon group was pseudo-axial. The

preference for a pseudo-axial position of the silyl group can

be explained on the basis of a stabilizing ground state

interaction between the s_C–Siand the p^p_CvC. This kind of

interaction has been proposed previously to rationalize the

preferred conformation of allylsilanes.¹⁹

1

(71%) and a better epimer ratio (13:1 determined by H

NMR).²⁰

Scheme 16. Reagents and conditions: (a) pyridine (3 equiv.), CH₃COCl

(2 equiv.), CH₂Cl₂, 4 h, rt, 92%; (b) Et₃BnNCl (0.1 equiv.), NaOH 50%,

CHCl₃, rt, 15 h; (c) ethyl diazoacetate (1.2 equiv.), Cu(acac)₂(2 mol%),

toluene, 90 8C, 3 h; (d) benzaldehyde (1.1 equiv.), TMSNTf₂(1.1 equiv.),

tBDMP (1.5 equiv.), CH₂Cl₂, 278 8C, 1 h.; (e) m-cpba (1 equiv.), 220 8C,

1 h; (f) N-methyl-1,2-oxido-1,2,3,4-tetrahydroisoquinoleine tetraﬂuoro-

borate 38 (1 equiv.), CH₂Cl₂, rt, 30 min.

Figure 1. Following the Monte Carlo conformational search—calculations

were considered to be convergent when each conformation was found at

least three times—a cluster analysis was performed with Xcluster 1.1. The

representative conformer of the cluster exhibiting calculated coupling

constants consistent with the one observed by ¹H NMR spectrum are shown

above. This cluster was also the one containing the conformer with the

lowest energy in the three cases.

7332

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

As the PhMe₂Si group was axial in 22b, we expected to

observe the reactivity typical of an allylsilane and attempted

a Sakurai reaction. In the presence of 1.1 equiv. of

TMSNTf₂22b reacted with benzaldehyde to yield 69% of

35 as a mixture of epimers (3:1).

beautiful illustration of the power of this synthetic strategy

for natural products synthesis.

We wanted to ﬁnd out whether this synthetic strategy could

be applied to the synthesis of enantiopure heterocyclic rings

such as dihydropyranes which could be useful intermediates

for the synthesis of glycomimetics. As a conclusion of these

studies, we want to show a ﬁrst illustration of this new

application (Scheme 18).

Epoxidation proved to be more difﬁcult. Treatment of 22b at

room temperature with m-cpba gave a complex mixture

probably due to the acidic nature of the oxidant. At 220 8C

only 13% of epoxide 36 were obtained along with 37% of 37

resulting from the rearrangement of the epoxide. The neutral

oxaziridinium salt 38²¹directly yielded alcohol 39 in 60%

yield.

Dihydroxylation of 22a yielded the diol 40 with an excellent

1

facial selectivity (only one isomer detected by H NMR of

the crude mixture) (Scheme 17). Dihydroxylation of 13

gave the triol 41 in good yield and the reaction was found to

be 99% diastereoselective. Only 1% of the cis-isomer could

be detected by GC-MS after protection of the 1,2-diol.

Chiral HPLC analysis showed that 42 was identical to the

product resulting from Sharpless dihydroxylation of cyclo-

hexadiene with AD-mix b followed by acetonide protec-

tion.²²These data further conﬁrmed the conﬁgurational

assignment of our RCM products.

Scheme 18. Reagents and conditions: (a) pyvaloyl chloride (1 equiv.),

solketal (1 equiv.), pyridine (1.1 equiv.), CH₂Cl₂, 48 h, 210 8C, 83%; (b)

HCl (2 N), THF, 16 h, rt, 98%; (c) NaIO₄(1.1 equiv.), water/CH₂Cl₂, 4 h,

rt, 71%; (d) n-BuLi (1.1 equiv.) in THF, 20 min, rt then (R,R)-Cl–

TiCpTADDOL (1.15 equiv.), 30 min, 278 8C then 43 (1 equiv), 3 h,

278 8C, 40% aqueous NH₄F, 15 h, rt, 56%; (e) TBSCl (1.5 equiv.),

imidazole (3 equiv.), 36 h, 60 8C, DMF; (f) TIPSCl (1.5 equiv), imidazole

(3 equiv.), 36 h, 60 8C, DMF; (g) DIBAL 1.5 M (2 equiv.), CH₂Cl₂,

278 8C, 1 h, 73%; (h) ethylvinyl ether, Hg(OAc)₂(1.1 equiv.), 48 h, 67%;

(i) 23 (25 mol%), CH₂Cl₂, reﬂux, 4 h, 93%.

Aldehyde 43 was prepared by standard procedures from

(þ/2)-solketal 44 and successfully submitted to allyl-

metallation. All our attempts to introduce a benzyl

protecting group on alcohol 45 failed and gave instead the

diene resulting from a Peterson elimination. A TBS group

could be easily introduced but, unexpectedly, attempts to

cleave the pivaloyl group by LiAlH₄also gave 2,4-

pentadien-1-ol. However the use of a more stable protecting

group such as TIPS allowed cleavage of the pivaloyl group

with DIBAL The resulting alcohol 47 was subsequently

vinylated by transetheriﬁcation in presence of Hg(OAc)₂.

25 mol% of catalyst 23 allowed a clean conversion of the

diene 48 into the cyclic vinyl ether 49.

Scheme 17. Reagents and conditions: (a) K₂OsO₄·2H₂O (2 mol%),

NMO·H₂O (1.7 equiv.), H₂O/THF, rt, 48 h; (b) dimethoxypropane

(1.5 equiv.), PTSA·H₂O cat., CH₂Cl₂, rt, 10 min; (c) NaH (1.3 equiv.),

THF, 55 8C, 5 h; (d) AD-mix b, MeSO₂NH₂, t-BuOH, H₂O, 3 8C, 2.25 h.

5. Conclusions and perspectives

In conclusion, we have demonstrated that the asymmetric

allylmetallation-ring-closing metathesis is an efﬁcient

sequence to access various polyfunctionalized rings with

good enantioselectivities. In this sequence, the bulk of the

silyl substituent plays a signiﬁcant role, favouring the RCM

reaction. The silyl group is also a key player in the further

transformations of the RCM products. Both the b-effect and

bulk of the axial silyl group are responsible for a complete

control of the facial selectivity in electrophilic additions to

the cyclic allylsilanes. The work of Roush et al. on the total

synthesis of conduritols and inositols is undoubtedly a

Further applications of this strategy will be reported in due

course.

6. Experimental

6.1. General

¹H NMR spectra and ¹³C NMR spectra were recorded in

CDCl₃at 400 and 100 MHz on a Bruker Avance 400

instrument or at 300 and 75 MHz on a Varian Gemini

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7333

300BB Instrument. Chemical shifts are reported in ppm

using residual CHCl₃(7.26 ppm) and CDCl₃(77 ppm) as

references. HPLC analyses were realized with a Waters

Alliance apparatus. The mass spectra under fast atom

bombardment (FAB) or chemical ionization (CI) were

recorded at 70 eV ionizing potential; CH₄–N₂O were used

for CI. The spectra are presented as m/z (% rel. int.). High

resolution mass spectra were performed in the laboratory of

bromide (1 M in Et₂O, 25 mL, 1.1 equiv.) at 0 8C was added

cis-hept-4-enal (2.5 g, 22 mmol, 1 equiv.) dropwise. After

15 min at 0 8C and 20 min at rt was added MeOH (1 mL,

1.1 equiv.) to quench excess Grignard reagent. 1.2 N HCl

(20 mL) was added and the organic phase was separated.

The aqueous phase was extracted with Et₂O. The combined

organic phases were dried over MgSO₄and concentrated

under reduced pressure to yield the crude alcohol in

quantitative yield (pure by NMR and GC). ¹H NMR

(CDCl₃): d 5.75–5.9 (m, 1H), 5.3–5.5 (m, 2H), 5.1–5.2

(2m, 2H), 3.67 (pseudo q, 1H, J¼6 Hz), 2–2.4 (m, 6H), 1.64

(br s, 1H), 1.45–1.6 (m, 2H), 0.97 (t, 3H, J¼7.5 Hz). ¹³C

NMR (CDCl₃): d 134.8, 132.3, 128.4, 118.2, 70.3, 41.9,

36.4, 23.5, 20.5, 14.4. IR (ﬁlm) n_maxcm²¹3364, 3077,

3006, 2963, 2932, 2874, 1441, 1067. MS(EI, 70 eV): 154

(7), 136 (16), 113 (58), 95 (100), 41 (57). HRMS: Calcd for

C₁₀H₁₈O: 154.13576 found: M 154.13593.

´

Prof. Flammang (Universite de Mons Hainaut) or at the

Cesamo Laboratory (Universite Bordeaux I). [a] were

´

measured on a Perkin–Elmer 241 MC polarimeter. Thin-

layer chromatographic analyses were performed on

MERCK 60 F₂₅₄silica gel plates (coated on aluminium).

Visualization was realized under UV lamp or KMnO₄

revelator. Flash chromatography separations were per-

formed using MERCK 60 40–63 mm silica and technical

grade solvents.

Reaction requiring anhydrous conditions were performed

using ﬂame-dried glassware under a positive pressure of

argon. Dry THF was distilled from potassium and

benzophenone under argon, CH₂Cl₂was distilled from

CaH₂, Et₂O and toluene were distilled from Na, DMF was

6.3.2. anti-3-Dimethylphenylsilyl-deca-1,7-diene-4-ol

(5rac). To a solution of allyldimethylphenylsilane (3.6 g,

21 mmol, 1.15 equiv.) in THF (100 mL) was added n-BuLi

2.2 M in hexane (9.3 mL, 1.15 equiv.) dropwise at room

temperature in 15 min. After 15 min, the solution was

cooled to 278 8C and a solution of ClTi(OiPr)₃(5.8 g,

1.25 equiv.) in THF (8 mL) was added dropwise. After

20 min at 278 8C, was added heptenal (2 g, 18 mmol,

1 equiv.). After 1.5 h of reaction, 45% NH₄F (75 mL) was

added and stirring was continued overnight. The reaction

mixture was ﬁltered of Celite and the organic phase was

separated. The aqueous phase was extracted with AcOEt.

The combined organic phases were dried over MgSO₄and

concentrated under reduced pressure. Flash chromatography

(SiO₂: CH₂Cl₂/hexane: 4:6) gave the homoallylic alcohol as

a light yellow oil in 88% yield (pure by NMR, .99% by

˚

dried over 3 A MS. 1st and 2nd generation Grubbs’ catalysts

3 and 23 were purchased from Strem Chemicals.

The calculations were performed on a SGI Octane platform

¨

running Macromodel version 6.5 (Schrodinger Inc.).

Conformational minima were found using the modiﬁed

MM3^p(1991 parameters) or MM2^p(1987 parameters) force

ﬁelds as implemented and completed in the macromodel

program. Build structures were minimized to a ﬁnal RMS

gradient #0.01 kJ A²¹mol²¹via the Truncated Newton

˚

Conjugated Gradient (TNCG) method (500 cycles).

Coupling constant calculations were performed using

Ref. 23 as implemented in Macromodel.

1

GC). TLC R_f0.48 (Et₂O/hexane, 3:17, KMnO₄). H NMR

(CDCl₃): d 7.3–7.6 (m, 5H), 5.83 (ddd, 1H, J¼17, 10.4,

10.4 Hz), 5.05 (dd, 1H, J¼10.3, 2 Hz), 4.91 (dd, 1H, J¼17,

2 Hz), 3.74 (pseudo q, 1H, J¼4.8 Hz), 1.93–2.1 (m, 4H),

1.9 (dd, 1H, J¼10.7, 4.4 Hz), 1.4–1.5 (m, 3H), 0.93 (t, 3H,

J¼7.4 Hz), 0.35 (s, 3H), 0.33 (s, 3H). ¹³C NMR (CDCl₃): d

137.9, 135.1, 134, 132.2, 129.1, 128.4, 127.7, 115.5, 71.2,

42.1, 37.1, 23.6, 20.5, 14.3, 23.5, 23.9. IR (ﬁlm) n_max

cm²¹3570, 3463, 3070, 3004, 2961, 2874, 1248, 1112.

MS(CI): 289 (2) [Mþ1]^þ, 271 (24), 137 (67), 135 (100).

Elem. Anal. Calcd for C₁₈H₂₈OSi C 74.94, H 9.78 found: C

74.45, H 9.72.

6.2. Reaction rate measurements

For the kinetics, a known amount of catalyst 3 (,10 mg)

was weighted in an NMR tube. Deuterated benzene

(0.6 mL) was added just before performing the NMR.

After addition of 20 mL of oleﬁn (,10 equiv. depending on

the oleﬁn) with a calibrated Hamilton syringe, an arrayed ¹H

NMR experiment was started taking spectra every 40 or

60 s. The delay between the addition of the oleﬁn and the

ﬁrst ¹H NMR acquisition was measured precisely to be able

to consider the point at the origin for the linear regression

analysis. Before each set of measurements, an experiment

with hexene was performed to ascertain reproducibility and

the quality of the catalyst. The experiment was repeated at

least two independent times. Pseudo-ﬁrst order rate

constants were measured from the integration of the

different RuvCH-X signals. First-order ﬁts were obtained

for all experiments under these pseudo-ﬁrst-order con-

ditions. Second-order rate constants were calculated from

pseudo-ﬁrst-order rate constants, k₁and k₂measured were

divided by the values obtained for hexene to give k₁rel and

k₂rel as listed in Table 1.

6.3.3. cis-3-Dimethylphenylsilyl-deca-1,7-diene-4-yl

acetate (6rac). To a solution of the alcohol 5rac (2 g,

6.9 mmol, 1 equiv.) and pyridine (2.3 mL, 4 equiv.) in

CH₂Cl₂(50 mL) at 0 8C was added AcCl (1.5 mL, 3 equiv.)

dropwise. The suspension was stirred for 1.5 h at rt Et₂O

(50 mL) was added and the reaction mixture was ﬁltered;

The ﬁltrate was concentrated under reduced pressure and

Et₂O (100 mL) was added. The organic phase was washed

twice with 1.2 N HCl and once with Na₂CO₃sat. The crude

alcohol was obtained in quantitative yield (pure by NMR,

1

99% by GC). TLC R_f0.76 (CH₂Cl₂, KMnO₄). H NMR

(CDCl₃): d 7.3–7.5 (m, 5H), 5.85 (ddd, 1H, J¼17.1, 11.3,

11.3 Hz), 5.05 (dd, 1H, J¼10, 2 Hz), 5.03 (dt, 1H, J¼6.9,

3.8 Hz), 4.89 (dd, 1H, J¼17, 1.9 Hz), 1.8–2.1 (m, 4H), 1.82

(s, 3H), 1.4–1.7 (m, 2H), 0.93 (t, 3H, J¼7.5 Hz), 0.33 (s,

3H), 0.31 (s, 3H). ¹³C NMR (CDCl₃): d 170.2, 137.3, 134.6,

6.3. Procedures

6.3.1. cis-Deca-1,7-diene-4-ol (4rac). To allylmagnesium

7334

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

133.9, 132.1, 129.1, 127.8, 127.6, 115.6, 73.7, 39.3, 33.9,

23, 20.5, 21.1, 14.3, 23.9, 24. IR (ﬁlm) n_maxcm²¹3072,

3051, 3007, 2962, 2934, 2874, 1739, 1237; MS(EI, 70 eV):

315 (2), 270 (2), 179 (16), 135 (100), 117 (57). Elem. Anal.

Calcd for C₂₀H₃₀O₂Si: C 72.67, H 8.96 found: C 72.57, H

8.96.

5H), 2.03 (dd, 1H, J¼10.7, 3.9 Hz), 1.85 (m, 2H), 1.85–2

(m, 2H), 1.82 (s, 3H), 1.4–1.7 (m, 2H), 0.33 (s, 3H), 0.31 (s,

3H). ¹³C NMR (CDCl₃): d 170.2, 137.7, 134.5, 133.9, 129.1,

127.7, 137.3, 115.7, 114.7, 73.4, 39.4, 33.1, 29.6, 21.1, 24.

IR (ﬁlm) n_maxcm²¹3072, 3001, 2956, 2857, 1739, 1237.

MS(CI): 243 (40), 179 (23), 135 (68), 117 (100). Elem.

Anal. Calcd for C₁₈H₂₆O₂Si C 71.47, H 8.66 found: C 71.45,

H 8.73.

6.3.4. anti-3-Dimethylphenylsilyl-oct-1,7-diene-4-ol

(7rac). To a solution of the allylsilane (8 g, 45.4 mmol,

1.15 equiv.) in THF(150 mL) at rt was added 2.1 M BuLi

(21.6 mL, 1.15 equiv.) dropwise. After 20 min, the orange

solution was cooled to 278 8C and a solution of ClTi(OiPr)₃

(14.8 g, 1.25 equiv.) in THF (20 mL) was added dropwise

over 10 min. After 15 min, the neat aldehyde (3.3 g,

40 mmol, 1 equiv.) was added over 5 min. After 2 h at

275 8C, the cooling bath was removed and 45% NH₄F

(160 mL) were added. After 4 h of hydrolysis, Et₂O

(100 mL) was added and the crude mixture was ﬁltered of

Celite. The solid residue was washed with Et₂O (4£50 mL)

and the organic layer was separated. The aqueous phase was

extracted once with Et₂O (100 mL). The combined organic

phases were dried over MgSO₄and concentrated under

reduced pressure. Flash chromatography (SiO₂: 100%

CH₂Cl₂) gave the homoallylic alcohol in 63–75% yield

(.99% pure by GC). For characterization see 19b.

6.3.7. 3-Cylcohexyl-oct-1,7-diene-4-yl t-butyldimethyl-

silyl ether (10rac). A solution of the alcohol 11rac

(594 mg, 2.85 mmol, 1 equiv.), imidazole (388 mg,

2 equiv.) and TBSCl (473 mg, 1.1 equiv.) in DMF (5 mL)

was heated overnight at 45–50 8C. Water (50 mL) and Et₂O

(40 mL) were added. The organic layer was separated and

washed with 1.2 N HCl. Puriﬁcation by ﬂash chromato-

graphy (SiO₂: 100% hexane) gave 73% yield of the silyl

ether as a colorless liquid (.99% by GC). TLC R_f0.79

(hexane, KMnO₄). ¹H NMR (CDCl₃): d 5.78 (ddt, 1H,

J¼17, 10.2, 6.8 Hz), 5.68 (ddd, 1H, J¼17.5, 9.9, 9.9 Hz),

3.85 (ddd, 1H, J¼7.9, 5.5, 2.5 Hz), 0.88 (s, 9H), 0.7–2.1 (m,

16H), 0.05 (s, 6H). ¹³C NMR (CDCl₃): d 138.7, 138.1,

116.4, 114.4, 71, 54.5, 36.7, 34.7, 31.8, 31.5, 29.7, 26.7,

26.5, 26.4, 25.9, 18.2, 23.8, 24.5. IR (KBr) n_maxcm²¹

3074, 2928, 2854, 1254, 1075. MS(EI, 70 eV): 307 (0.5)

[M2Me]^þ; 265 (76), 199 (100). HRMS Calcd for

C₂₀H₃₈OSi 323.277020 found: M 323.276936. Elem.

Anal. Calcd for C₂₀H₃₈OSi C 74.46, H 11.87 found: C

74.54, H 12.00.

6.3.5. anti-3-Dimethylphenylsilyl-oct-1,7-diene-4-yl

t-butyl-dimethylsilyl ether (8rac). A solution of the

alcohol (2.2 g, 8.5 mmol, 1 equiv.) and TBDMSCl (1.5 g,

1.2 equiv.) in DMF (10 mL) was stirred at 50 8C for 36 h.

Water (150 mL) was added and the reaction mixture was

extracted with Et₂O. The combined organic layers were

dried over MgSO₄and concentrated in vacuo. Flash

chromatography (100%, hexane) gave the silyl ether in

83% yield (.99% d.e. and .99% pure by GC). TLC R_f0.97

6.3.8. 3-Cyclohexyl-oct-1,7-diene-4-ol (11rac). To a green

suspension of CrCl₂(1.23 g, 10 mmol, 2 equiv.) and

4-pentenal (420 mg, 5 mmol, 1 equiv.) in THF (20 mL)

was added allylbromide (1.03 g, 5 mmol, 1 equiv.). After

15 h of reaction, 1.2 N HCl (10 mL) and Et₂O (20 mL) were

added to the resulting purple reaction mixture. After 30 min

of hydrolysis, the organic layer was separated and the

aqueous phase extracted with Et₂O. The combined organic

phases were dried over MgSO₄and concentrated in vacuo.

Flash chromatography (SiO₂: 100% CH₂Cl₂) gave the

homoallylic alcohol in 61–71% yield. TLC R_f0.5

1

(CH₂Cl₂, KMnO₄). H NMR (CDCl₃): d 7.3–7.6 (m, 5H),

5.85 (ddd, 1H, J¼17.3, 10.3, 10.3 Hz), 5.7 (ddt, 1H, J¼17,

10.5, 6.5 Hz), 4.7–5 (m, 4H), 3.87 (ddd, 1H, J¼8, 5,

3.3 Hz), 2.03 (dd, 1H, J¼10.4, 3.3 Hz), 1.8–2.1 (m, 2H),

1.4–1.7 (m, 2H), 0.88 (s, 9H), 0.35 (s, 3H), 0.31 (s, 3H),

0.01 (s, 3H), 20.01 (s, 3H). ¹³C NMR (CDCl₃): d 138.7,

138.5, 135.8, 134.1, 128.8, 127.5, 114.5, 114.4, 72.8, 40.4,

35.8, 29.8, 26.1, 18.2, 23.1, 23.7, 23.9. MS(EI, 70 eV):

319 (22), 317 (15), 209 (100), 135 (83). IR (ﬁlm) n_maxcm²¹

3072, 3052, 2999, 2956, 2930, 2858, 1254, 1063. Elem.

Anal. Calcd for C₂₂H₃₈OSi₂C 70.52, H 10.22 found: C

70.40, H 10.52.

1

(CH₂Cl₂, KMnO₄). H NMR (CDCl₃): d 5.84 (ddt, 1H,

J¼17.1, 10.3, 6.8 Hz), 5.7 (ddd, 1H, J¼17.2, 10.2, 10.2 Hz),

5.2 (dd, 1H, J¼10.3, 2.3 Hz), 5–5.1 (m, 2H), 3.74 (d pseudo

q, 1H, J¼9.3, 4.7 Hz), 2–2.2 (m, 2H), 1.41 (d, 1H,

J¼4.4 Hz), 0.8–1.8 (m, 13H). ¹³C NMR (CDCl₃): d

138.7, 136.9, 118.5, 114.7, 69.9, 56.1, 36.7, 34.4, 31.7,

29.9, 26.6, 26.54, 26.48 (note: the cHex shows

diastereotopic carbons giving thus 5 signals instead of 3).

IR (ﬁlm) n_maxcm²¹3385, 3075, 2925, 2853, 1641,

1449, 911. MS(CI): 415 (100) [MþM21], 359 (12),

307 (48), 291 (72), 151 (40), 99 (10), 83 (28). Elem.

Anal. Calcd for C₁₄H₂₄O C 80.71, H 11.61 found: C 80.36,

H 11.61.

6.3.6. anti-3-Dimethylphenylsilyl-oct-1,7-diene-4-yl

acetate (9rac). To a solution of the alcohol (3 g,

11.5 mmol, 1 equiv.) and pyridine (3.65 mL, 4 equiv.) in

CH₂Cl₂(75 mL) at 0 8C was added AcCl (2.46 mL,

3 equiv.) dropwise. After 30 min at rt, Et₂O (75 mL) was

added, the reaction mixture was ﬁltered of Celite and

concentrated in vacuo. The residue was taken up in Et₂O

(150 mL) and was washed twice with 1.2 N HCl and once

with Na₂CO₃sat. The organic phase was dried over MgSO₄

and concentrated under reduced pressure to afford the crude

acetate (98% by GC) in quantitative yield. Filtration over

SiO₂(CH₂Cl₂100%) gave analytically pure acetate in 95%

yield (99% pure by GC). TLC R_f0.8 (CH₂Cl₂, KMnO₄). ¹H

NMR (CDCl₃): d 7.3–7.5 (m, 5H), 5.85 (ddd, 1H, J¼17.2,

10.4, 10.4 Hz), 5.7 (ddt, 1H, J¼17, 10.4, 6.4), 4.8–5.1 (m,

6.3.9. Cyclohex-3-enol (12rac). To a reﬂuxing solution of

the diene 4rac (120 mg, 0.78 mmol, 1 equiv.), was added 3

(10 mg, 1.6 mol%), in CH₂Cl₂(0.7 mL). The reaction

reached completion after less than 10 min (TLC and GC).

The solvent was removed under reduced pressure to give a

quantitative yield of crude cyclohexenol 12rac²⁴(.99% by

GC). ¹H NMR (CDCl₃): d 5.68 (dm, 1H, J¼11.3 Hz), 5.56

(dm, 1H, J¼10.6 Hz), 3.95 (br, 1H), 1.5–2.5 (m, 7H).

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7335

6.3.10. cis-2-Dimethylphenylsilyl-cyclohexy-3-enol

(13rac). To a reﬂuxing solution of the diene (365 mg,

1.27 mmol, 1 equiv.) in CH₂Cl₂(16 mL) was added 3

(16 mg, 1.6 mol%) in CH₂Cl₂(1 mL). After 41 h of reaction

the solvent was evaporated under reduce pressure. Flash

chromatography (SiO₂, hexane/Et₂O, 17:3) gave the

cyclohexene in 86% yield (.99% by GC). For character-

ization see 13ent.

solution of allyldimethylphenylsilane (5.3 g, 30 mmol,

1.15 equiv.) in THF (40 mL) at rt was added 2.1 M

n-BuLi (14.3 mL, 1.15 equiv.) dropwise over 10 min.

After 20 min, the yellow solution was transferred via canula

over 10 min to a suspension of (R,R)-TiClCpTADDOL

(20 g, 32.6 mmol, 1.25 equiv.) in THF (150 mL) at 278 8C.

After 30 min, neat aldehyde (1 equiv.) was added over

4 min. The reaction was continued for 3 h at 278 8C. AcOEt

(50 mL) and 45% NH₄F (200 mL) were added and the

heterogeneous mixture was ﬁltered of Celite and the solid

residue was washed with Et₂O (90 mL). The organic layer

was separated and the aqueous phase was extracted twice

with Et₂O (70 mL). The combined organic layers were dried

over MgSO₄and concentrated in vacuo. Hexane (300 mL)

was added to precipitate (R,R)-TADDOL. After 20 min

stirring, the mixture was ﬁltered. Evaporation of the solvent

followed by ﬂash chromatography gave the enantioenriched

homoallylic alcohol.

6.3.11. 3-Dimethylphenylsilyl-deca-1,7-diene-4-yl

acetate (14rac). Via RCM of 6rac. To a reﬂuxing solution

ofthediene(258 mg, 0.78 mmol, 1 equiv.)inCH₂Cl₂(10 mL)

was added 3 (10 mg, 1.6 mol%) in CH₂Cl₂(0.7 mL). After

23 h of reaction the solvent was evaporated under reduced

pressure. Flash chromatography (SiO₂, hexane/Et₂O, 8:2)

gave the acetate in 91% yield (.99% by GC).

Via RCM of 8rac. To a solution of the diene (1.5 g,

4.96 mmol, 1 equiv.) in CH₂Cl₂(35 mL) at rt was added 3

(15 mg, 0.3 mol%) in three portions in 20 min intervals. The

reaction mixture was concentrated in vacuo and was stirred

in MeOH (20 mL) for 45 min. The solvent was evaporated

and ﬂash chromatography gave the acetate in 88% yield

(.99% yield). TLC R_f0.45 (hexane/Et₂O, 8:2, KMnO₄).

[a]²_D³¼þ108 (c¼0.64 in CH₂Cl₂). ¹H NMR (CDCl₃): d 7.3–

7.6 (m, 5H), 5.6–5.7 (m, 1H, J¼10.1, 3.3, 3.3 Hz), 5.5–5.6

(m, 1H, J¼10.1, 3.3 Hz), 5.22 (ddd, 1H, J¼8, 5.7, 3 Hz),

2.28 (m, 1H), 2–2.1 (m, 2H), 1.75–1.9 (m, 1H), 1.81 (s,

3H), 1.63 (d pseudo-t d, 1H, J¼13, 7, 7, 3 Hz), 0.36 (s, 3H),

0.35 (s, 3H). ¹³C NMR (CDCl₃): d 170.5, 138.4, 133.7,

128.9, 127.7, 125, 124.6, 71.9, 31.6, 26.4, 22.1, 21.1, 23,

23.2. IR (ﬁlm) n_maxcm²¹3068, 3031, 2962, 2913, 2840,

1732, 1247. MS(CI): 214 (2),179 (11), 137 (26), 135 (89),

117 (100), 80 (81). Elem. Anal. Calcd for C₁₆H₂₂O₂Si C

70.03, H 8.08 found: C 69.91, H 8.19.

6.3.15. (3S,4R)-anti-3-(Dimethyl-phenyl-silanyl)-hepta-

1,6-dien-4-ol (19a). Following the typical procedure A. To

a solution of allyldimethylphenylsilane (3.8 g, 22 mmol,

1 equiv.) in THF (33 mL) at rt was added 2.1 M n-BuLi

(12 mL, 1.15 equiv.) dropwise over 10 min. After 20 min,

the yellow solution was transferred via canula over 10 min

to

a suspension of (R,R)-TiClCpTADDOL (16.7 g,

27.2 mmol, 1.25 equiv.) in THF (125 mL) at 278 8C.

After 30 min, 3-butenal (2 g in solution in 10 mL CH₂Cl₂,

freshly synthesized and kept at 278 8C before use,

29 mmol, 1.15 equiv.) was added. Chromatography (SiO₂:

CH₂Cl₂/cyclohexane, 3:2) 3.68 g (68% yield). [a]²_D³¼24.56

(c¼1.23 in CHCl₃). TLC R_f0.57 (CH₂Cl₂: cyclohexane,

1

3:2, KMnO₄). H NMR (CDCl₃): d 7.48 (m, 2H), 7.28 (m,

3H), 5.80 (ddd, 1H, J¼17.4, 10.5, 10.3 Hz), 5.65 (dddd, 1H,

J¼17.1, 10.3, 7.6, 6.8 Hz), 4.97 (m, 3H), 4.82 (ddd, 1H,

J¼17.1, 2.2, 0.7 Hz), 3.69 (m, 1H, J¼7.6, 5.4, 3.7, 1.0 Hz),

2.09 (m, 2H), 1.83 (dd, 1H, J¼10.5, 3.7 Hz), 1.53 (d, 1H,

J¼1 Hz), 0.37 (s, 3H), 0.33 (s, 3H). ¹³C NMR (CDCl₃): d

138.3, 135.6, 135.3, 134.5, 129.5, 128.1, 118.2, 115.9, 70.7,

42.3, 42.0, 23.2, 23.6. IR (ﬁlm) n_maxcm²¹3577, 3464,

3071, 2972, 2902, 1639, 1625, 1427, 1248, 1113. MS(CI):

229 (49) [M2OH]^þ, 209 (8), 205 (22), 135 (100), 127 (16),

94 (33), 79 (23), 75 (27). HRMS Calcd for C₁₅H₂₁Si

[M2OH]^þ229.141469 found: M 229.141254. Elem. Anal.

found: C 72.68, H 9.16 Calcd for C₁₅H₂₂OSi C 73.11, H 9.00.

6.3.12. cis-2-Dimethylphenylsilyl-cyclohex-3-enyl

t-butyldimethylphenylsilyl ether (15rac). To a reﬂuxing

solution of the diene 9rac (292 mg, 0.78 mmol, 1 equiv.) in

CH₂Cl₂(1 mL) was added a solution of 3 (1 mL of a 3.2 mg

cata/10 mL CH₂Cl₂solution, 0.05 mol%). After com-

pletion, the ﬂask was open to air for 1 h and the reaction

mixture was concentrated in vacuo. Flash ﬁltration over

SiO₂(100% hexane) gave 15rac (98% yield, .99% pure by

GC). For analyses see 22b.

6.3.13. cis-2-Cyclohexyl-cyclohex-3-enyl t-butyl-

dimethylsilyl ether (16rac). To a solution of the diene

(252 mg, 0.78 mmol, 1 equiv.) in CH₂Cl₂(10 mL) was

added Grubbs catalyst (1.6 mol%, 10 mg) in CH₂Cl₂

(0.7 mL). After 5 min of reaction, the solvent was removed

under reduced pressure and the residue was chromato-

graphed (SiO₂: 100% hexane) to give 16rac in 98% yield.

¹H NMR (CDCl₃): d 5.68 (dm, 1H, J¼11 Hz), 5.61 (br d,

1H, J¼11 Hz), 4.12 (br, 1H), 2.1–2.3 (m, 1H), 1.4–2 and

0.8–1.3 (m, 15H), 0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H).

¹³C NMR (CDCl₃): d 126.7, 126.5, 67.6, 46.3, 37.4, 31.9,

30.8, 29.8, 26.6, 25.9, 21.9, 18.2, 24, 25. IR (ﬁlm) n_max

cm²¹3031, 2926, 2854, 1252, 1079. MS(EI, 70 eV): 279

(1), 237 (100), 219 (12), 161 (24). HRMS: Calcd for

C₁₈H₃₄OSi 294.237894 found: M 294.237078.

6.3.16. (3S,4R)-anti-3-(Dimethyl-phenyl-silanyl)-octa-

1,7-dien-4-ol (19b). Following the typical procedure A. To

a solution of allyldimethylphenylsilane (5.3 g, 30 mmol,

1.15 equiv.) in THF (40 mL) at rt was added 2.1 M n-BuLi

(14.3 mL, 1.15 equiv.) dropwise over 10 min. After 20 min,

the yellow solution was transferred via canula over 10 min

to

a

suspension of (R,R)-TiClCpTADDOL (20 g,

32.6 mmol, 1.25 equiv.) in THF (150 mL) at 278 8C.

After 30 min, neat 4-pentenal (2.2 g, 26.1 mmol, 1 equiv.)

was added. [a]_D²³¼21 (c¼1.1 in CH₂Cl₂). TLC R_f0.55

1

(CH₂Cl₂, KMnO₄). H NMR (CDCl₃): d 7.3–7.6 (m, 5H),

5.84 (ddd, 1H, J¼17, 10.5, 10.5 Hz), 5.74 (ddt, 1H, J¼17,

10, 6.7 Hz), 4.85–5.1 (m, 4H), 3.75 (m, 1H), 2.04 (pseudo q,

2H, J¼7 Hz), 1.91 (dd, 1H, J¼10.4, 4.4 Hz), 1.49 (pseudo q,

2H, J¼6.8 Hz), 1.44 (d, 1H, J¼4.1 Hz), 0.36 (s, 3H), 0.34

(s, 3H). ¹³C NMR (CDCl₃): d 138.4, 135.1, 134.1, 129.1,

127.8, 127.9, 115.6, 114.6, 71, 42.1, 36.2, 30.2, 23.4, 23.9.

6.3.14. Asymmetric allylation: typical procedure A. To a

7336

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

IR (ﬁlm) n_maxcm²¹3582, 3455, 3070, 3051, 2956, 2932,

1428, 1249, 1113. MS(CI): 261 (2) [Mþ1]^þ, 243 (26), 153

(21), 137 (50), 135 (100), 109 (72). Elem. Anal. Calcd for

C₁₆H₂₄OSi C 73.79, H 9.29 found: C 73.68, H 9.29.

TLC R_f0.61 (CH₂Cl₂/PE, 1:1, KMnO₄). [a]²_D³¼20.4

1

(c¼1.04 in CHCl₃). H NMR (CDCl₃): d 7.56 (m, 2H),

7.38 (m, 3H), 5.86 (ddd, 1H, J¼17.1, 10.5, 10.2 Hz), 5.82

(ddt, 1H, J¼17.1, 10.2, 6.7 Hz), 5.08 (dd, 1H, J¼10.2,

2 Hz), 5.02 (ddt, 1H, J¼17.3, 2, 1.5 Hz), 4.95 (ddt, 1H,

J¼10.2, 2, 1.2 Hz), 4.94 (dd, 1H, J¼17.1, 2 Hz), 3.74 (m,

1H, J¼11.7, 4.6 Hz), 2.06 (td, 2H, J¼7.5, 6.7 Hz), 1.93 (dd,

1H, J¼10.5, 4.5 Hz), 1.2 (m, 12H), 0.38 and 0.35 (s, 3H).

¹³C NMR (CDCl₃): d 139.6, 138.4, 135.6, 134.4, 129.5,

128.2, 115.3, 114.5, 71.9, 42.5, 37.5, 34.2, 29.89, 29.87,

29.8, 29.5, 29.3, 26.1, 22.9, 23.1. IR (ﬁlm)n_maxcm²¹

3573, 3447, 3070, 2920, 2850, 1640, 1625, 1427, 1250,

1113, 1054, 998, 907, 832, 814, 733, 700. MS(CI): 345

[MþH]^þ(5), 286 (15), 271 (100), 209 (72), 152 (17), 137

(95), 135 (36), 75 (37). HRMS Calcd for C₂₂H₃₅OSi

[M2H]^þ343.245719 found: M 343.244560.

6.3.17. (3S,4R)-anti-3-(Dimethyl-phenyl-silanyl)-nona-

1,8-dien-4-ol (19c). Following the typical procedure A. To

a solution of allyldimethylphenylsilane (6.2 g, 35.2 mmol,

1.15 equiv.) in THF (47 mL) at rt was added 2.3 M n-BuLi

(15.3 mL, 1.15 equiv.) dropwise over 10 min. After 20 min,

the yellow solution was transferred via canula over 10 min

to

a suspension of (R,R)-TiClCpTADDOL (24.4 g,

37.6 mmol, 1.25 equiv.) in THF (175 mL) at 278 8C.

After 30 min, neat 5-hexenal (3 g, 30.6 mmol, 1 equiv.)

was added. Chromatography (SiO₂: AcOEt/PE, 5:95) 6.25 g

1

(75% yield). TLC R_f0.45 (CH₂Cl₂, KMnO₄). H NMR

(CDCl₃): d 7.53 (m, 2H), 7.36 (m, 3H), 5.83 (ddd, 1H,

J¼17.1, 10.5, 10.2 Hz), 5.73 (ddt, 1H, J¼17.0, 10.2,

6.7 Hz), 5.06 (dd, 1H, J¼10.2, 1.9 Hz), 4.93 (m, 3H), 3.74

(m, 1H), 1.93 (m, 3H), 1.37 (m, 5H), 0.36 (s, 3H), 0.33 (s,

3H). ¹³C NMR (CDCl₃): d 138.7, 137.9, 135.1, 133.9, 129.0,

127.7, 115.6, 114.4, 71.2, 42.1, 36.5, 33.4, 25.0, 23.4,

24.0. IR (ﬁlm) n_maxcm²¹3571, 3449, 3069, 2932, 2858,

1640, 1625, 1427, 1250, 1113, 1053, 998, 908, 832, 814,

733, 700. MS(CI): 257 (10) [M2OH]þ, 209 (5), 205 (5),

179 (8), 135 (100), 122 (17), 107 (15), 81 (20), 75 (27).

HRMS Calcd for C₁₇H₂₆OSi [M]^þ274.175294 found: M

274.174264.

6.4. Protection of the alcohol by an acetyl group: typical

procedure B

To solution of the alcohol (1 equiv.) and pyridine

(3.5 equiv.) in CH₂Cl₂(43 equiv.) at 0 8C is added dropwise

acetyl chloride (2.5 equiv.). The reaction mixture is stirred

at room temperature for 4 h. CH₂Cl₂is added and the

organic phase is washed twice with HCl 0.1 N. The aqueous

phase is extracted with CH₂Cl₂and the combined organic

layers are washed twice with NH₄Clsat, dried over MgSO₄

and concentrated in vacuo. Flash chromatography gave the

acetyl protected alcohol.

6.3.18. (3S,4R)-anti-3-(Dimethyl-phenyl-silanyl)-deca-

1,9-dien-4-ol (19d). Following the typical procedure A. To

a solution of allyldimethylphenylsilane (5.4 g, 30.6 mmol,

1.15 equiv.) in THF (40 mL) at rt was added 2.3 M n-BuLi

(13.3 mL, 1.15 equiv.) dropwise over 10 min. After 20 min,

the yellow solution was transferred via canula over 10 min

6.4.1. (3S,4R)-anti-3-Dimethylphenylsilyl-nona-1,8-

diene-4-yl acetate (20c). Following the typical procedure

B. The reaction was carried out on 0.3 g of 19a (1.09 mmol).

Flash chromatography (SiO₂: CH₂Cl₂) gave 0.332 g of

colorless oil (95% yield). TLC R_f0.75 (CH₂Cl₂, KMnO₄).

¹H NMR (CDCl₃): d 7.46 (m, 2H), 7.34 (m, 3H), 5.82 (ddd,

1H, J¼17.1, 10.5, 10.2 Hz), 5.71 (ddt, 1H, J¼16.8, 10.2,

7 Hz), 4.84–5.05 (m, 5H), 2.01 (dd, 1H, J¼10.5, 3.6 Hz),

1.94 (dt, 2H, J¼7.2, 6.6 Hz), 1.82 (s, 3H), 1.46 (m, 2H), 1.26

(m, 2H), 0.49 and 0.47 (s, 3H). ¹³C NMR (CDCl₃): d 170.4,

138.5, 137.5, 134.8, 134.1, 129.2, 127.8, 115.7, 114.8, 74.0,

39.7, 33.7, 33.6, 24.8, 21.4, 23.6, 23.7. MS(CI): 288 (9),

257 (15), 179 (34), 154 (17), 135 (100), 123 (25), 117 (89),

107 (16), 80 (17). HRMS Calcd for C₁₇H₂₅Si [M2AcO²]^þ

257.172554 found: M 257.173270.

to

a suspension of (R,R)-TiClCpTADDOL (21.2 g,

32.6 mmol, 1.25 equiv.) in THF (175 mL) at 278 8C.

After 30 min, neat 6-heptenal (3 g, 26.7 mmol, 1 equiv.)

was added. Chromatography (SiO₂: AcOEt/PE, 5:95) 5.15 g

1

(67% yield). TLC R_f0.42 (CH₂Cl₂, KMnO₄). H NMR

(CDCl₃): d 7.56 (m, 2H), 7.38 (m, 3H), 5.85 (ddd, 1H,

J¼17.1, 10.5, 10.3 Hz), 5.78 (ddt, 1H, J¼17.1, 10.2,

6.7 Hz), 5.07 (dd, 1H, J¼10.3, 2.1 Hz), 4.96 (m, 3H),3.74

(m, 1H), 1.99 (m, 2H), 1.93 (dd, 1H, J¼10.5, 4.5 Hz), 1.39

(m, 2H), 1.29 (m, 4H), 0.38 and 0.35 (s, 3H). ¹³C NMR

(CDCl₃): d 139.3, 138.4, 135.6, 134.4, 129.5, 128.2, 116.0,

114.7, 71.8, 42.5, 37.4, 34.1, 29.2, 25.6, 22.9, 23.5. IR (ﬁlm)

6.4.2. (3S,4R)-anti-3-Dimethylphenylsilyl-tetradeca-

1,13-diene-4-yl acetate (20e). Following the typical

procedure B. The reaction was carried out on 0.5 g of 19e

(1.45 mmol). Flash chromatography (SiO₂: CH₂Cl₂) gave

n

_maxcm²¹3582, 3445, 3071, 2930, 2856, 1641, 1625, 1428,

1249, 1113, 1046, 999, 902, 834, 815, 734, 701. MS(CI): 288

(5), 271 (3), 209 (7), 135 (100), 75 (21). HRMS: Calcd for

C₁₈H₂₇OSi [M2H]^þ287.183119 found: M 287.183177.

1

0.545 g of colorless oil (97% yield). H NMR (CDCl₃): d

7.48 (m, 2H), 7.37 (m, 3H), 5.38 (m, 2H), 4.96 (m, 5H), 2.04

(m, 3H), 1.84 (s, 3H), 1.47 (m, 2H), 1.37 (m, 2H), 1.21 (m,

10H), 0.34 and 0.32 (s, 3H). ¹³C NMR (CDCl₃): d 170.2,

139.1, 137.6, 134.8, 133.9, 129.1, 127.7, 115.5, 114.1, 74.1,

39.6, 34.0, 33.8, 29.4 (2 carbons), 29.3, 29.1, 28.9, 25.2,

21.1, 23.8, 23.9. IR (ﬁlm) n_maxcm²¹3071, 2921, 2852,

1736, 1640, 1626, 1461, 1427, 1370, 1237, 1113, 1019, 904,

833, 700. MS(CI): 329 (100) [Mþ12CH₃CO–CH₃]^þ, 327

(33), 192 (8), 179 (10), 135 (39), 117 (41).

6.3.19. (3S,4R)-anti-3-(Dimethyl-phenyl-silanyl)-tetra-

deca-1,13-dien-4-ol (19e). Following the typical procedure

A. To a solution of allyldimethylphenylsilane (0.59 g,

3.36 mmol, 1.15 equiv.) in THF (40 mL) at rt was added

2.2 M n-BuLi (1.52 mL, 1.15 equiv.) dropwise over 10 min.

After 20 min, the yellow solution was transferred via canula

over 10 min to a suspension of (R,R)-TiClCpTADDOL

(2.33 g, 3.58 mmol, 1.25 equiv.) in THF (175 mL) at

278 8C. After 30 min, neat undecylenic aldehyde (0.5 g,

3 mmol, 1 equiv.) was added. Chromatography (SiO₂:

AcOEt/PE, 5:95) gave 0.73 g of colorless oil (71% yield).

6.4.3. Protection of the alcohol by a TBS: typical

procedure C. To a solution of TBSCl (1.5 equiv.) in

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7337

DMF (12 equiv.) was added imidazole (4 equiv.). The

reaction mixture was heated to 60 8C for 1.2 h before to

add the alcohol (1 equiv.). The reaction was monitored

by GC. After 48 h the reaction was complete and 1/2

volume of NH₄Clsat were added. The aqueous phase was

extracted with pentane (3£1 volume) and the combined

organic phase were dried over MgSO₄and concentrated in

vacuo. Flash chromatography gave the TBS-protected

alcohol.

1H), 1.28 (m, 1H), 1.14 (m, 1H), 0.87 (s, 9H), 0.34 and 0.29

(s, 3H), 0.00 and 20.01 (s, 3H). ¹³C NMR (CDCl₃): d 139.3,

139.2, 136.4, 134.5, 129.1, 127.9, 114.84, 114.82, 73.6,

41.1, 36.7, 34.1, 26.5, 25.2, 18.7, 22.6, 23.29, 23.31and

23.5. IR (ﬁlm) n_maxcm²¹3070, 2927, 2857, 1641, 1625,

1471, 1463, 1427, 1413, 1253, 1112, 1061, 907, 834, 772,

732. MS(CI): 388 (1) [M]^þ, 331 (12), 319 (21), 209 (85),

193 (17),135 (100), 107 (15), 75 (73), 73 (57). HRMS:

Calcd for C₂₃H₄₀OSi₂(M2H): 387.25394 found: M

387.25367.

6.4.4. (3S,4R)-anti-3-Dimethylphenylsilyl-hepta-1,6-

diene-4-yl t-butyldimethylsilyl ether (21a). Following

the typical procedure C. The reaction was carried out on

1.7 g of 19a (6.9 mmol). Flash chromatography (SiO₂: PE)

gave 2.12 g of colorless oil (85% yield, .99% pure by GC).

[a]²_D³¼þ2.91 (c¼0.55 in CHCl₃). TLC R_f0.58 (PE,

KMnO₄). ¹H NMR (CDCl₃): d 7.51 (m, 2H), 7.35 (m,

3H), 5.90 (ddd, 1H, J¼17.4, 10.4, 10.2 Hz), 5.64 (dddd, 1H,

J¼17.1, 10.2, 7.5, 6.7 Hz), 4.99 (m, 3H), 4.77 (dd, 1H,

J¼17.4, 1.7 Hz), 3.91 (ddd, 1H, J¼8.0, 4.8, 2.8 Hz), 2.32

(m, 1H, J¼13.0, 8.0, 7.5 Hz), 2.21 (m, 1H, J¼13.0, 6.7,

4.8 Hz), 2.08 (dd, 1H, J¼10.4, 2.8 Hz), 0.89 (s, 9H), 0.36

and 0.31 (s, 3H), 0.04 and 0.01 (s, 3H). ¹³C NMR (CDCl₃): d

138.9, 135.9, 135.4, 134.5, 129.2, 127.9, 117.5, 115.3, 73.2,

41.9, 40.5, 26.5, 18.6, 22.8, 23.3, 23.4, 23.5. IR (ﬁlm)

n_maxcm²¹3072, 2956, 2858, 1626, 1472, 1428, 1361,

1254, 1090, 939, 834, 774, 732. MS(FAB): 359 (2), 345

(1), 319 (14), 303, 251, 209 (24), 193, 147, 135 (100).

HRMS: Calcd for C₂₁H₃₅O₁Si (M2H): 359.22264 found:

M 359.22193.

6.4.7. (3S,4R)-anti-3-Dimethylphenylsilyl-deca-1,9-

diene-4-yl t-butyldimethylsilyl ether (21d). Following

the typical procedure C. The reaction was carried out on

1.6 g of 19d (5.5 mmol). Flash chromatography (SiO₂:

cyclohexane) gave 1.76 g of colorless oil (79% yield, 99%

pure by GC). [a]²_D³¼22.53 (c¼0.83 in CHCl₃). TLC R_f0.47

(PE, KMnO₄). ¹H NMR (CDCl₃): d 7.50 (m, 2H), 7.34 (m,

3H), 5.84 (ddd, 1H, J¼17.1, 10.4, 10.2 Hz), 5.77 (ddt, 1H,

J¼17.1, 10.2, 6.7 Hz), 4.94 (m, 3H), 4.74 (m, 2H, J¼17.1,

2.2 Hz), 3.83 (m, 1H, J¼7.9, 4.5, 3.5 Hz), 1.99 (m, 3H),

1.52 (m, 1H), 1.39 (m, 1H), 1.20 (m, 4H), 0.87 (s, 9H), 0.34

and 0.29 (s, 3H), 0.00 and 20.01 (s, 3H). ¹³C NMR

(CDCl₃): d 139.3, 139.2, 136.3, 134.4, 129.1, 127.9, 114.8,

114.7, 73.8, 41.1, 37.2, 34.2, 29.4, 26.6, 25.5, 18.8, 22.5,

23.1, 23.2, 23.3. IR (ﬁlm) n_maxcm²¹3070, 2950, 2928,

2855, 1624, 1471, 1462, 1427, 1253, 1111, 1059, 1019, 905,

834, 773, 700. MS(FAB): 425 (3) [MþNa]^þ, 401 (6)

[M2H]^þ, 387 (3), 345 (10), 329 (9), 319 (20), 288 (92), 267

(8), 251 (9), 227 (5), 209 (100). HRMS: Calcd for

C₂₄H₄₂OSi₂(M2H): 401.26959 found: M 401.26943.

6.4.5. (3S,4R)-anti-3-Dimethylphenylsilyl-octa-1,7-diene-

4-yl t-butyldimethylsilyl ether (21b). Following the typical

procedure C. The reaction was carried out on 6 g of 19b

(23 mmol). Flash chromatography (SiO₂: PE) gave 7.77 g of

colorless oil (90% yield, .99% pure by GC). [a]²_D³¼21.00

6.4.8. (3S,4R)-anti-3-Dimethylphenylsilyl-tetradeca-

1,13-diene-4-yl t-butyldimethylsilyl ether (21e). Follow-

ing the typical procedure C. the reaction was carried out on

2 g of 19e (5.8 mmol). Flash chromatography (SiO₂: PE)

gave 2.39 g of colorless oil (90% yield, 98% pure by GC).

1

(c¼1.16 in CHCl₃). TLC R_f0.46 (hexane, KMnO₄). H

1

NMR (CDCl₃): d 7.3–7.6 (m, 5H), 5.85 (ddd, 1H, J¼17.3,

10.3, 10.3 Hz), 5.7 (ddt, 1H, J¼17, 10.5, 6.5 Hz), 4.7–5 (m,

4H), 3.87 (ddd, 1H, J¼8, 5, 3.3 Hz), 2.03 (dd, 1H, J¼10.4,

3.3 Hz), 1.8–2.1 (m, 2H), 1.4–1.7 (m, 2H), 0.88 (s, 9H),

0.35 (s, 3H), 0.31 (s, 3H), 0.01 (s, 3H), 20.01 (s, 3H). ¹³C

NMR (CDCl₃): d 138.7, 138.5, 135.8, 134.1, 128.8, 127.5,

114.5, 114.4, 72.8, 40.4, 35.8, 29.8, 26.1, 18.2, 23.1, 23.7,

23.9. IR (ﬁlm) n_maxcm²¹3072, 3052, 2999, 2956, 2930,

2858, 1254, 1063. MS(EI, 70 eV): 319 (22), 317 (15), 209

(100), 135 (83). MS(CI): 375 [MþH]^þ(1), 359 (2), 319 (7),

251 (14), 209 (100), 189 (14), 147 (16), 135 (14). HRMS:

Calcd for C₂₂H₃₉OSi₂[MþH]^þ375.253948 found: M

375.253989. Elem. Anal. Calcd for C₂₂H₃₈OSi₂C 70.52,

H 10.22 found: C 70.40, H 10.52.

TLC R_f0.68 (PE, KMnO₄). H NMR (CDCl₃): d 7.52 (m,

2H), 7.35 (m, 3H), 5.85 (m, 2H), 4.98 (d, 2H, J¼17.1 Hz),

4.94 (d, 2H, J¼10.2 Hz), 4.76 (d, 1H, J¼17.1 Hz), 3.85 (m,

1H, J¼7.5, 3.7 Hz), 2.05 (m, 3H), 1.40 (m, 2H), 1.25 (m,

12H), 0.89 (s, 9H), 0.37 and 0.32 (s, 3H), 0.02 and 0.01 (s,

3H). ¹³C NMR (CDCl₃): d 139.6, 139.3, 136.5, 134.5, 129.1,

127.9, 114.7, 114.5, 73.8, 41.0, 37.3, 34.2, 30.0, 29.9, 29.8,

29.5, 29.3, 26.5, 25.8, 18.6, 22.6, 23.2, 23.3, 23.5. IR

(ﬁlm) n_maxcm²¹3070, 2927, 2854, 1640, 1625, 1471, 1462,

1427, 1413, 1252, 1061, 907, 834, 772, 732. MS(CI): 459

(20) [MþH]^þ, 444 (27), 401 (30), 319 (72), 283 (18), 251

(67), 209 (77), 189 (42), 135 (100). HRMS: Calcd for

C₂₈H₅₀OSi₂458.340023 found: M 458.340914.

6.4.9. (1R,2S)-2-(Dimethylphenylsilanyl)-cyclohex-3-

enol (13ent). To a boiling solution of 19b (2.5 g,

0.96 mmol, 1 equiv.) in CH₂Cl₂(120 mL) was added 3

(400 mg, 5 mol%) in CH₂Cl₂(3 mL). After 2 h of reaction

the conversion was complete. The solvent was evaporated

under reduced pressure. Flash chromatography (SiO₂,

CH₂Cl₂/EP, 1:1) gave 1.92 g of 13ent (87% yield).

[a]²_D³¼þ81.9 (c¼0.7 in CH₂Cl₂). TLC R_f0.35 (Et₂O/

6.4.6. (3S,4R)-anti-3-Dimethylphenylsilyl-nona-1,8-

diene-4-yl t-butyldimethylsilyl ether (21c). Following

the typical procedure C. The reaction was carried out on

1.6 g of 19c (5.8 mmol). Flash chromatography (SiO₂: PE)

gave 1.65 g of colorless oil (72% yield, 98% pure by GC).

[a]²_D³¼23.87 (c¼1.12 in CHCl₃). TLC R_f0.53 (PE,

KMnO₄). ¹H NMR (CDCl₃): d 7.52 (m, 2H), 7.36 (m,

3H), 5.86 (ddd, 1H, J¼17.2, 10.5, 10.2 Hz), 5.74 (ddt, 1H,

J¼17.2, 10.2, 6.7 Hz), 4.95 (m, 3H), 4.77 (dd, 1H, J¼17.2,

1.7 Hz), 3.86 (m, 1H, J¼7.9, 3.5 Hz), 2.03 (dd, 1H, J¼10.2,

3.5 Hz), 1.94 (m, 2H, J¼6.7 Hz), 1.51 (m, 1H), 1.41 (m,

1

hexane, 3:17, KMnO₄). H NMR (CDCl₃): d 7.3–7.7 (m,

5H), 5.67 (dm, 1H, J¼10.5 Hz), 5.57 (d, 1H, J¼10.8 Hz),

4.2 (br s, 1H), 2–2.2 (m, 3H), 1.5–1.8 (m, 2H), 1.44 (d, 1H,

J¼6 Hz), 0.40 an 0.38 (s, 3H). ¹³C NMR (CDCl₃): d 138.8,

7338

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

134, 128.9, 127.7, 125.1, 124.7, 68, 34.3, 29.8, 21.2, 23.1,

23.2. IR (ﬁlm) n_maxcm²¹3578, 3456, 3068, 3020, 2952,

2921, 2841, 1427, 1247. MS(CI): 215 (32), 155 (20), 137

(61), 135 (100). HRMS: Calcd for C₁₄H₁₉Si (Mþ1–H₂0)

215.125604 found: M 215.12500.

6.4.12. (1R,2S)-2-(Dimethylphenylsilanyl)-cyclohept-3-

enyl t-butyldimethylphenylsilyl ether (22c). To a solution

of 21c (200 mg, 0.514 mmol, 1 equiv.) in toluene (30 mL)

was added 3 (32 mg, 7.5 mol%) in toluene (1 mL). The

reaction mixture was heated at 60 8C for 2 h then the ﬂask

was open to air then the solvent was evaporated under

reduced pressure. Flash chromatography (SiO₂: hexane)

gave 173 mg of 22c (93% yield). [a]²_D³¼þ48.27 (c¼0.98 in

CHCl₃). TLC R_f0.5 (Cyclohexane, KMnO₄). ¹H NMR

(CDCl₃): d 7.57 (m, 2H), 7.35 (m, 3H), 5.65 (m, 1H,

J¼11.6, 7.39, 4.01 Hz), 5.53 (m, 1H, J¼11.6, 8.5, 2.5 Hz),

3.95 (ddd, 1H, J¼11.3, 4.5, 4.1 Hz), 2.35 (dd, 1H, J¼8.5,

4.1 Hz), 2.05 (dddd, 1H, J¼16.1, 7.4, 6.7, 2.5 Hz), 1.88 (m,

1H, J¼13.7, 11.0, 4.0 Hz), 1.73 (m, 1H, J¼11.0, 4.0 Hz),

1.67 (m, 1H, J¼16.1, 4.1, 2.5 Hz), 1.55 (m, 1H, J¼14.0, 6.7,

2.0 Hz), 1.23 (m, 1H, J¼8.0, 2.5 Hz), 0.92 (s, 9H), 0.47 and

0.43 (s, 3H), 0.06 and 0.05 (s, 3H). ¹³C NMR (CDCl₃): d

140.2, 134.2, 129.5, 128.6, 128.5, 127.4, 75.2, 42.4, 38.9,

28.3, 26.1, 24.4, 18.2, 20.6, 21.1, 24.7, 24.8. IR (ﬁlm)

6.4.10. (1R,2S)-2-(Dimethylphenylsilanyl)-cyclopent-3-

enyl t-butyldimethylphenylsilyl ether (22a). To a solution

of 21a (1.6 g, 4.43 mmol, 1 equiv.) in CH₂Cl₂(215 mL) was

added 3 (73 mg, 2 mol%) in CH₂Cl₂(2 mL). After 5 min of

reaction the ﬂask was open to air for 1 h then the solvent was

evaporated under reduced pressure. Flash chromatography

(SiO₂: hexane) gave 1.45 g of 22a (98% yield).

[a]²_D³¼þ94.2 (c¼0.75 in CHCl₃). TLC R_f0.67 (PE,

KMnO₄). ¹H NMR (CDCl₃): d 7.54 (m, 2H), 7.33 (m,

3H), 5.51 (m, 2H), 4.96 (dd, 1H, J¼8.5, 7.3 Hz), 2.49 (m,

2H, J¼8.5 Hz), 2.18 (m, 1H, J¼14.9, 7.3, 2.2 Hz), 0.87 (s,

9H), 0.38 and 0.35 (s, 3H), 0.03 and 20.02 (s, 3H). ¹³C

NMR (CDCl₃): d 140.5, 134.3, 131.9, 128.8, 127.8, 125.7,

77.5, 42.75, 42.72, 26.5, 18.5, 21.8, 22.7, 24.34, 24.36.

IR (ﬁlm) n_maxcm²¹3053, 2955, 2929, 2857, 1471, 1427,

1362, 1253, 1094, 898, 835, 776, 700. MS(CI): 331 (5)

[M2H]^þ, 251 (44), 209 (100), 189 (11), 147 (18), 135 (39).

n

_maxcm²¹3070, 2950, 2868, 1471, 1392, 1254, 1141, 1070,

1021, 832, 791. MS(FAB): 360 (1), 303(2), 209 (73), 193

(20), 134.9 (100), 106.8 (11), 93.9 (82), 78.9 (30), 74.9 (30).

HRMS: Calcd for C₂₁H₃₅OSi₂(M2H): 359.22264 found: M

359.22213.

6.4.11. (1R,2S)-2-(Dimethylphenylsilanyl)-cyclohex-3-

enyl t-butyldimethylphenylsilyl ether (22b). To a solution

of 21b (292 mg, 0.78 mmol, 1 equiv.) in CH₂Cl₂(10 mL)

was added 3 (10 mg, 1.6 mol%) in CH₂Cl₂(0.7 mL). After

2 min of reaction the ﬂask was open to air then the solvent

was evaporated under reduced pressure. Flash chromatog-

raphy (SiO₂: hexane) gave 265 mg of 22b (98% yield).

[a]²_D³¼þ74.1 (c¼1.35 in CH₂Cl₂). TLC R_f0.63 (hexane,

KMnO₄). ¹H NMR (CDCl₃): d 7.53 (m, 2H), 7.33 (m, 3H),

5.47 (m, 1H, J¼9.9, 4.5, 3.1 Hz), 5.41 (m, 1H, J¼9.9, 4.6,

1.8 Hz), 4.22 (ddd, 1H, J¼10.5, 6.5, 4.1 Hz), 2.19 (m, 1H),

2.04 (m, 2H), 1.59 (m, 2H), 0.88 (s, 9H), 0.38 and 0.37 (s,

3H), 0.05 and 0.00 (s, 3H). ¹³C NMR (CDCl₃): d 140, 134.2,

128.5, 127.5, 127.2, 123.6, 71.5, 36.1, 30.6, 24.7, 26.2, 18.4,

21.3, 22, 24.3, 24.8. IR (ﬁlm) n_maxcm²¹3096, 3050,

3024, 2955, 2930, 2857, 1252, 1081. MS(CI): 345 (100)

[M2H]^þ, 303 (25), 283 (33), 269 (44), 251 (57), 227 (60),

209 (69), 189 (25), 135 (51), 80 (32). Elem. Anal. Calcd for

C₂₀H₃₄OSi₂C 69.10, H 9.89 found: C 69.10, H 9.98.

6.4.13. (3S,4R)-anti-3-Dimethylphenylsilyl-dodeca-1,9-

diene-4-yl t-butyldimethylsilyl ether (26). (3S,4R)-anti-

3-(Dimethyl-phenyl-silanyl)-dodeca-1,9-dien-4-ol. Follow-

ing the typical procedure A. To a solution of allyldimethyl-

phenylsilane (2 g, 11.3 mmol, 1.1 equiv.) in THF (25 mL) at

rt was added 2.2 M n-BuLi (5.15 mL, 1.1 equiv.) dropwise

over 10 min. After 20 min, the yellow solution was

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7339

transferred via canula over 10 min to a suspension of (R,R)-

TiClCpTADDOL (7.6 g, 11.8 mmol, 1.15 equiv.) in THF

(30 mL) at 278 8C. After 30 min, neat cis-6-nonenal

(1.72 mL, 10.3 mmol, 1 equiv.) was added. Chromato-

graphy (SiO₂: AcOEt/PE, 4:96) 2.08 g (64% yield).

[a]²_D³¼þ1.36 (c¼1.1 in CHCl₃). TLC R_f0.54 (CH₂Cl₂,

KMnO₄). ¹H NMR (CDCl₃): d 7.54 (m, 2H), 7.36 (m, 3H),

5.83 (ddd, 1H, J¼17.2, 10.5, 10.4 Hz), 5.33 (m, 2H), 5.05

(dd, 1H, J¼10.4, 2.1 Hz), 4.91 (dd, 1H, J¼17.2, 2.1 Hz),

3.72 (m, 1H), 2.01 (m, 4H), 1.90 (dd, 1H, J¼10.5, 4.5 Hz),

1.32 (m, 6H), 0.94 (t, 2H, J¼7.6 Hz), 0.36 and 0.33 (s, 3H).

¹³C NMR (CDCl₃): d 138.0, 135.2, 133.8, 131.7, 129.0 (2

carbons), 127.7, 115.5, 71.5, 42.2, 37.1, 29.7, 27.3, 25.4,

20.5, 14.3, 23.3, 23.9. IR (ﬁlm) n_maxcm²¹3446, 3070,

2969, 2869, 1716, 1625, 1428, 1380, 1250, 1142, 1021, 900,

834, 701. MS(CI): 315 (6) [M2H]þ, 299 (3), 271 (10), 247

(15), 229 (5), 209 (7), 205 (10), 187 (14), 135 (100), 81 (45).

HRMS: Calcd for C₂₀H₃₁OSi [M2H]^þ315.214419 found:

M 315.2144612. (26) Following the typical procedure

C. The reaction was carried out on 0.77 g of (3S,4R)-anti-

3-(dimethyl-phenyl-silanyl)-dodeca-1,9-dien-4-ol (2.44 mmol).

Flash chromatography (SiO₂: cyclohexane) gave 0.67 g of

colorless oil (63% yield). ¹H NMR (CDCl₃): d 7.50 (m, 2H),

7.34 (m, 3H), 5.84 (ddd, 1H, J¼17.2, 10.4, 10.2 Hz), 5.32

(m, 2H), 4.94 (dd, 1H, J¼10.2, 2.1 Hz), 4.75 (dd, 1H,

J¼17.2, 2.1 Hz), 3.84 (m, 1H, J¼8.0, 4.5, 3.2 Hz), 1.99 (m,

5H, J¼7.6 Hz), 1.51 (m, 1H), 1.39 (m, 1H), 1.17 (m, 4H),

0.96 (t, 3H, J¼7.6 Hz), 0.88 (s, 9H), 0.35 and 0.30 (s, 3H),

0.01 and 20.01 (s, 3H). ¹³C NMR (CDCl₃): d 138.8, 135.9,

134.1, 131.6, 129.1, 128.7, 127.5, 114.4, 73.3, 40.6, 36.7,

29.7, 27.1, 26.1, 25.1, 20.5, 18.2, 14.4, 23.1, 23.6, 23.7,

23.9. MS(CI): 431 (19) [Mþ1]^þ, 430 (15) [M], 416

[M2Me]^þ, 373 (44), 319 (100) [M2(CH₂)₄–CvC–Et]^þ,

299 (8), 295 (10), 251 (71), 209 (84), 189 (35), 135 (100).

HRMS: Calcd for C₂₆H₄₇OSi₂[MþH]^þ431.316548 found:

M 431.314734.

(34), 68 (45). HRMS: Calcd for C₁₉H₂₈O₃SiNa (MþNa)

355.17054 found: M 355.17023.

6.4.15. Acetic acid 2-(dimethyl-phenyl-silanyl)-1-(2,2-

dimethyl-5-vinyl-[1,3]dioxolan-4-yl)-but-3-enyl ester

(29). Following the typical procedure B. The reaction was

carried out on 1.2 g of 28 (3.25 mmol). Flash chromato-

graphy (SiO₂, CH₂Cl₂/PE, 3:2) gave 1.08 g of colorless oil

(89% yield). [a]²_D³¼þ2.91 (c¼0.96 in CHCl₃). TLC R_f0.83

1

(CH₂Cl₂/PE, 3:2, KMnO₄). H NMR (CDCl₃): d 7.44 (m,

2H), 7.35 (m, 3H), 5.94 (ddd, 1H, J¼17.1, 10.7, 10.1 Hz),

5.83 (ddd, 1H, J¼17.1, 10.1, 9.1 Hz), 5.05 (dd, 1H, J¼10.1,

1.7 Hz), 4.83 (dd, 1H, J¼17.1, 1.7 Hz), 4.39 (dd, 1H, J¼8.5,

5.9 Hz), 4.19 (dd, 1H, J¼8.8, 5.9 Hz), 2.00 (dd, 1H, J¼10.7,

2.4 Hz), 1.78 (s, 3H), 1.43 and 1.27 (s, 3H), 0.32 and 0.27 (s,

3H). ¹³C NMR (CDCl₃): d 170.1, 137.2, 134.9, 134.5, 134.4,

129.6, 128.0, 119.6, 116.4, 109.2, 79.0, 78.7, 70.6, 37.5, 28.3,

26.0, 21.4, 23.4, 24.2. IR (ﬁlm) n_maxcm²¹3071, 2958, 1743,

1626, 1428, 1371, 1233, 1113, 1048, 874, 835, 757, 735.

MS(FAB): 397 (100) [MþNa]^þ, 329 (32), 288 (17), 267 (22),

257 (47), 237 (17), 217 (21), 209 (46). HRMS: Calcd for

C₂₁H₃₀O₄SiNa 397.18110 found: M 397.18095.

6.4.16. Acetic acid 5-(dimethyl-phenyl-silanyl)-2,2-

dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-yl

ester (30). To a solution of 29 (840 mg, 0.22 mmol,

1 equiv.) in CH₂Cl₂(30 mL) were added 2nd generation

Grubbs’ catalyst (160 mg, 8 mol%, 0.018 mmol). The

reaction mixture was heated at reﬂux and argon was

bubbled for 2 h. Flash chromatography (SiO₂: CH₂Cl₂)

gave 632 mg (80% yield) of 30 as a colorless oil.

[a]²_D³¼þ5.32 (c¼1.39 in CHCl₃). TLC R_f0.19 (CH₂Cl₂,

1

KMnO₄). H NMR (CDCl₃): d 7.5 (m, 2H), 7.37 (m, 3H),

5.87 (dd, 1H, J¼9.9, 5.5 Hz), 5.80 (ddd, 1H, J¼9.9, 3.4,

1.4 Hz), 5.07 (dd, 1H, J¼9.2, 6.4 Hz), 4.39 (dd, 1H, J¼6.6,

3.4 Hz), 4.01 (dd, 1H, J¼9.2, 6.6 Hz), 2.63 (dd, 1H, J¼6.4,

5.5 Hz), 1.78 (s, 3H), 1.42 (s, 3H), 1.30 (s, 3H), 0.36 (s, 3H),

0.35 (s, 3H). ¹³C NMR (CDCl₃): d 171.2, 137.6, 134.3,

131.6, 129.8, 128.3, 122.2, 109.4, 75.2, 75.0, 72.8, 41.3,

32.5, 28.4, 26.0, 21.3, 22.3, 22.6. IR (ﬁlm) n_maxcm²¹

3069, 2924, 2852, 1744, 1624, 1459, 1369, 1230, 1112,

1049, 1018, 834, 812, 733, 701. MS(FAB): 369 (50)

[MþNa]^þ, 355 (10), 341 (11), 329 (100), 288 (29), 280 (23),

271 (14), 267 (13), 245 (11), 229 (19), 226 (17), 223 (27),

209 (97), 207 (36). HRMS: Calcd for C₁₉H₂₆O₄SiNa

(MþNa) 369.1498 found: M 369.1510.

6.4.14. 2-(Dimethyl-phenyl-silanyl)-1-(2,2-dimethyl-5-

vinyl-[1,3]dioxolan-4-yl)-but-3-en-1-ol (28). Following

the typical procedure A. To a solution of allyldimethyl-

phenylsilane (2.7 g, 15.5 mmol, 1.1 equiv.) in THF (30 mL)

at rt was added 2.2 M n-BuLi (7 mL, 1.1 equiv.) dropwise

over 10 min. After 20 min, the yellow solution was

transferred via canula over 10 min to a suspension of

(R,R)-TiClCpTADDOL (10.4 g, 16.2 mmol, 1.15 equiv.) in

THF (40 mL) at 278 8C. After 30 min, the neat alcohol 28

(2.2 g, 14 mmol, 1 equiv.) was added. Chromatography

(SiO₂: CH₂Cl₂) 3.1 g (55% yield). [a]²_D³¼233.4 (c¼0.99 in

CHCl₃). TLC R_f0.42 (CH₂Cl₂, KMnO₄). ¹H NMR (CDCl₃):

d 7.52 (m, 2H), 7.36 (m, 3H), 5.99 (ddd, 1H, J¼17.1, 10.8,

10.2 Hz), 5.70 (ddd, 1H, J¼17.1, 10.2, 8.5 Hz), 5.28 (ddd,

1H, J¼17.1, 1.6, 0.7 Hz), 5.22 (ddd, 1H, J¼10.2, 1.6,

0.7 Hz), 4.98 (dd, 1H, J¼10.2, 2.0 Hz), 4.79 (ddd, 1H,

J¼17.1, 2.0 Hz), 4.39 (dd, 1H, J¼8.5, 6.1 Hz), 4.01 (dd, 1H,

J¼8.5, 6.1 Hz), 3.69 (ddd, 1H, J¼8.5, 2.6, 2.5 Hz), 2.15 (dd,

1H, J¼2.6, 1.9 Hz), 1.90 (ddd, 1H, J¼10.8, 2.5, 1.9 Hz),

1.44 (s, 3H), 1.32 (s, 3H), 0.37 (s, 3H), 0.31 (s, 3H). ¹³C

NMR (CDCl₃): d 138.1, 134.9, 134.8, 134.5, 129.4, 128.0,

119.2, 115.2, 108.9, 80.7, 78.7, 70.0, 37.9, 28.5, 25.9, 23.4,

23.7. IR (ﬁlm) n_maxcm²¹3490, 3070, 2986, 2902, 1624,

1471, 1427, 1371, 1246, 1114, 1068, 835. MS(CI): 331 (1)

[M2H]þ, 317 (4) [M2Me]þ, 259 (19), 257 (23), 205 (31),

203 (36), 144 (17), 137 (56), 135 (100), 124 (28), 98 (24), 75

6.5. Addition of dicholorocarbene: typical procedure D

To a mixture of the cyclic allylsilane (0.62 mmol, 1 equiv.)

and Et₃BnNCl (15 mg, 0.065 mmol, 0.1 equiv.) in CHCl₃

(4 mL) was added 50% NaOH (1 mL) under vigorous

stirring. After 15 h, water (4 mL) was added and the

organic layer was separated. The aqueous phase was

extracted with CHCl₃. The combined organic phases

were dried over MgSO₄and concentred in vacuo.

Puriﬁcation by ﬂash chromatography gave the

dichlorocyclopropane.

6.5.1. (1R,2S,3R,5R)-3-(tert-Butyl-dimethyl-silanyloxy)-

6,6-dichloro-2-(dimethyl-phenyl-silanyl)-bicyclo[3.1.0]-

hexane (31). Following procedure D, the reaction was

carried out on 206 mg (0.62 mmol) of 22a. Chromatography

7340

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

(SiO₂: cyclohexane) gave 252 mg of colorless oil (98%

yield). [a]²_D³¼210.1 (c¼1.3 in CDCl₃). TLC R_f0.64

(cyclohexane, KMnO₄). ¹H NMR (CDCl₃): d 7.56 (m,

2H), 7.36 (m, 3H), 4.60 (ddd, 1H, J¼7.5, 7.0, 5.3 Hz), 2.23

(ddd, 1H, J¼14.3, 7.0, 0.6 Hz), 2.10 (ddd, 1H, J¼8.1, 6.5,

0.6 Hz), 2.05 (dd, 1H, J¼7.5, 1.5 Hz), 1.98 (dd, 1H, J¼8.1,

1.5 Hz), 1.91 (ddd, 1H, J¼14.3, 6.5, 5.3 Hz), 0.85 (s, 9H),

0.41 and 0.39 (s, 3H), 0.01 and 20.06 (s, 3H). ¹³C NMR

(CDCl₃): d 139.7, 134.2, 129.2, 128.2, 78.4, 70.3, 39.6, 38.8,

36.5, 35.9, 26.5, 18.5, 21.2, 22.1, 24.1, 24.3. IR (ﬁlm)

128.2, 71.3, 69.8, 42.1, 35.1, 33.4, 32.0, 27.3, 26.6, 21.9,

18.6, 22.5, 22.5, 24.1, 24.3. IR (ﬁlm) n_maxcm²¹3069,

2954, 2856, 1471, 1427, 1255, 1089, 1043, 1017, 916, 830,

772, 731, 700, 607. MS(FAB): 441 [M2H]^þ(1), 385 (1),

327 (2), 307 (2), 288, 255 (6), 251, 228, 209 (65), 193, 179,

147, 135 (95), 105, 93, 73. HRMS: Calcd for C₂₂H₃₆OSi₂-

Cl₂442.168178 found: M 442.167339.

6.5.4. 3-(tert-Butyl-dimethyl-silanyloxy)-2-(dimethyl-

phenyl-silanyl)-bicyclo[4.1.0]heptane-7-carboxylic acid

ethyl ester (34). Compound 22b (300 mg, 0.831 mmol,

1 equiv.) was added to a suspension of copper acetyl-

acetonate (4.5 mg, 0.017 mmol, 2 mol%) in freshly dried

and degassed toluene (1 mL). The mixture was heated at

90 8C and ethyl diazoacetate (118 mg, 0.998 mmol,

1.2 equiv.) in toluene (2 mL) was added over 3 h thanks to

a syringe pomp. The brown reaction mixture was cooled to

room temperature and the solvent was removed under

reduce pressure (temperature of the water bath below

35 8C). The resulting oil was treated with 500 mg of alumine

to remove the catalyst. Pentane was added before ﬁltration

and concentration. The oil was chromatographed on SiO₂

(AcOEt/PE: 2.5:97.5) to give 266 mg (71% yield) of 34..

[a]²_D³¼þ44.11 (c¼1.33 in CHCl₃). TLC R_f0.28 (AcOEt/

PE: 3:97, KMnO₄). ¹H NMR (CDCl₃): d 7.54 (m, 2H), 7.31

(m, 3H), 4.06 (qd, 2H, J¼7.2, 2.3 Hz), 3.93 (m, 1H, J¼6,

3.3, 1.8 Hz), 2.14 (m, 1H, J¼13.7, 11.3, 6.5, 1.8 Hz), 1.70

(m, 1H, J¼14.4, 6.5 Hz), 1.70 (m, 1H, J¼9.7, 5.8, 4.3 Hz),

1.62 (m, 1H, J¼13.7, 6, 5.8 Hz), 1.52 (m, 1H, J¼9.7, 4.3,

3.3 Hz), 1.30 (dd, 1H, J¼4.3, 4.3 Hz), 1.23 (m, 1H, J¼3.3,

3.3 Hz), 1.20 (t, 3H, J¼7.2 Hz), 1.14 (m, 1H, J¼13.7, 11.3,

6.5, 1.8 Hz), 0.90 (s, 9H), 0.38 and 0.37 (s, 3H), 0.01 and

20.06 (s, 3H). ¹³C NMR (CDCl₃): d 174.3, 138.9, 133.8,

128.6, 127.6, 66.6, 60.0, 31.5, 28.9, 27.9, 26.1, 21.9, 21.7,

18.2, 17.0, 14.2, 22.9, 23.4, 24.1, 24.4. IR (ﬁlm) n_max

cm²¹2954, 2858, 1723, 1427, 1317, 1300, 1255, 1200,

1174, 1113, 1036, 986, 831, 700. MS(FAB): 455 (9)

[MþNa]^þ, 431 (5), 387 (9), 355 (7), 345 (6), 301 (16),288

(10), 251 (13), 223 (7), 209 (100). HRMS: Calcd for

C₂₄H₃₉O₃Si₂(M2H): 431.24377 found: M 431.24350.

n

_maxcm²¹3071, 2954, 2929, 2857, 1471, 1427, 1361, 1255,

1143, 1110, 1058, 888, 834, 778, 731, 700. MS(CI): 414 (2)

[M]^þ, 379 (2) [M2Cl]^þ, 325 (5), 283 (7), 251 (35), 209

(75), 189 (30), 154 (40), 135 (71), 113 (47), 75 (15), 59

(100). HRMS Calcd for C₂₀H₃₂Cl₂OSi₂414.136878 found:

M 414.137426.

6.5.2. (1R,2S,3R,6R)-7,7-Dichloro-2-dimethylphenyl-

silyl-bicyclo[4.1.0]heptan-3-yl acetate (32). Acetic acid

2-(dimethylphenylsilanyl)-cyclohex-3-enyl ester. To a sol-

ution of 13ent (374 mg, 1.6 mmol, 1 equiv.) and pyridine

(0.39 mL, 3 equiv.) in CH₂Cl₂(6 mL) at 0 8C was added

AcCl (0.23 mL, 2 equiv.) dropwise. After 1 h at rt, Et₂O

(7 mL) was added, the reaction mixture was ﬁltered and

concentrated in vacuo. The residue was taken up in Et₂O

(12 mL), ﬁltered, washed twice with 1.2 N HCl (3 mL) and

once with Na₂CO₃sat (3 mL). The organic phase was dried

over MgSO₄and concentrated under reduced pressure to

afford the crude acetate. Filtration over SiO₂(hexane/Et₂O,

8:2) gave pure acetate in 92% yield (.99% by GC, 92% ee

by HPLC) [a]²_D³¼þ108 (c¼0.64 in CH₂Cl₂). For analyses

see 14rac. (32) Following procedure D, the reaction was

carried out on 170 mg (0.62 mmol) of acetic acid

2-(dimethylphenylsilanyl)-cyclohex-3-enyl ester. Chroma-

tography (SiO₂: hexane 90:10 AcEt) gave 32 in 84% yield

(93% ee by HPLC, only one isomer detected by NMR, GC

and HPLC). [a]_D²³¼24 (c¼0.5 in CH₂Cl₂). TLC R_f0.3

(hexane/AcOEt, 9:1, KMnO₄). ¹H NMR (CDCl₃): d 7.3–7.6

(m, 5H), 4.98 (ddd, 1H, J¼3.9, 2.5, 2.5 Hz), 1.92 (s, 3H),

1.3-1.4 and 1.6–1.9 (m, 6H), 1.17 (dd, 1H, J¼5, 2.8 Hz),

0.42 (s, 3H), 0.39 (s, 3H). ¹³C NMR (CDCl₃): d 170.2,

136.7, 133.8, 129.4, 128, 67.9, 67.3, 26, 25.6, 23.7, 23.7,

13.8, 21.2, 23.9, 24. IR (ﬁlm) n_maxcm²¹3070, 3049,

3014, 2957, 2861, 1737, 1372, 1239, 1207. MS(EI, 70 eV):

179 (17), 135 (100), 117 (92), 127 (49), 43 (37). Elem. Anal.

Calcd for C₁₇H₂₂Cl₂O₂Si C 57.14, H 6.21, Cl 19.93 found:

C 57.23, H 6.22, Cl 19.93.

6.5.5. (1R,4R)-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclo-

hex-2-enyl]-phenyl-methanol (35). To a solution of 2,6-

di-t-butyl-4-methylpyridine

(266 mg,

1.29 mmol,

1.5 equiv.) and TMSNTf₂(305 mg, 0.86 mmol, 1 equiv.)

in CH₂Cl₂(5 mL) at 278 8C was added benzaldehyde

(97 mL, 0.95 mmol, 1.1 equiv.). After 10 min, 22c (300 mg,

0.86 mmol, 1 equiv.) was added and the reaction mixture

was stirred at 278 8C for 1 h. HCl (5 mL) were added and

the organic phase was washed with NaHCO₃sat. The

combined organic phases were dried over MgSO₄and

concentrated in vacuo. The oil was puriﬁed by chromato-

graphy (SiO₂, CH₂Cl₂/EP: 1:1). The product was isolated as

a 3:1 mixture of epimers. Analyses of enriched major

6.5.3. (1R,2S,3R,7R)-3-(tert-Butyl-dimethyl-silanyl-oxy)-

8,8-dichloro-2-(dimethyl-phenyl-silanyl)-bicyclo-

[5.1.0]octane (33). Following procedure D, the reaction was

carried out on 224 mg (0.62 mmol) of 22c. Chromatography

(SiO₂: cyclohexane) gave 250 mg of colorless oil (98%

yield) as a 10:1 mixture of diastereosiomers. [a]²_D³¼212.8

1

(c¼1.1 in CHCl₃). TLC R_f0.59 (PE, KMnO₄). H NMR

isomer: TLC R_f0.18 (CH₂Cl₂/EP, 2:3, KMnO₄). H NMR

(C₆D₆): d 7.66 (m, 2H), 7.32 (m, 3H), 4.22 (dd, 1H, J¼4.8,

1.4 Hz), 1.99 (m, 1H, J¼11.6, 11.6 Hz), 1.99 (m, 1H,

J¼12.6, 6.8 Hz), 1.82 (m, 1H, J¼13, 4.8 Hz), 1.77 (m, 1H,

J¼11.6, 11.6, 6.8 Hz), 1.72 (m, 1H, J¼13, 13, 12.7 Hz),

1.33 (m, 1H, J¼13, 12.6, 11.6 Hz), 1.29 (m, 1H, J¼13,

3.4 Hz), 1.17 (d, 1H, J¼11.6 Hz), 1.01 (s, 9H), 0.9 (m, 1H,

J¼13, 12.7, 3.4, 1.4 Hz), 0.63 and 0.56 (s, 3H), 0.04 and

20.01 (s, 3H). ¹³C NMR (CDCl₃): d 138.3, 134.5, 129.4,

(CDCl₃): 7.38 (m, 5H), 5.95 and 5.65 (dm, 1H, J¼10.3,

1.5 Hz), 4.26 (d, 1H, J¼8.1 Hz), 4.18 (m, 1H), 2.44

(m, 1H), 1.85 (m, 1H), 1.40 (m, 1H, J¼13, 9, 3 Hz), 1.28

(m, 1H) 1.09 (m, 1H, J¼13, 10, 3 Hz), 0.88 (s, 9H), 0.06

and 0.05 (s, 3H). ¹³C NMR (CDCl₃):143.4, 133.2, 130.2,

129.8, 128.0, 127.6, 79.7, 68.5, 44.3, 32.6, 26.3, 24.6, 18.6,

24.1, 24.3. MS(FAB): 341 (21) [MþNa]þ, 317 (8), 301

(37), 281 (62), 267 (31), 241 (21), 221 (100), 211 (25).

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7341

HRMS Calcd for C₁₉H₃₀O₂NaSi 341.191279 found: M

341.192469.

(180 mg, 56% yield). [a]²_D³¼28.2 (c¼1.03 in CH₂Cl₂).

1

TLC R_f0.64 (cyclohexane, KMnO₄). H NMR (CDCl₃): d

7.56 (m, 2H), 7.36 (m, 3H), 4.60 (ddd, 1H, J¼7.5, 7.0,

5.3 Hz), 2.23 (ddd, 1H, J¼14.3, 7.0, 0.6 Hz), 2.10 (ddd, 1H,

J¼8.1, 6.5, 0.6 Hz), 2.05 (dd, 1H, J¼7.5, 1.5 Hz), 1.98 (dd,

1H, J¼8.1, 1.5 Hz), 1.91 (ddd, 1H, J¼14.3, 6.5, 5.3 Hz),

0.85 (s, 9H), 0.41 and 0.39 (s, 3H), 0.01 and 20.06 (s, 3H).

¹³C NMR (CDCl₃): d 139.7, 134.2, 129.2, 128.2, 78.4, 70.3,

39.6, 38.8, 36.5, 35.9, 26.5, 18.5, 21.2, 22.1, 24.1, 24.3.

IR (ﬁlm) n_maxcm²¹2955, 2857, 1471, 1427, 1255, 1110,

1068, 888, 700. MS(CI): 365 (4) [M2H]^þ, 349 (68), 331

(14), 271 (15), 251 (72), 209 (100), 197 (53), 149 (63), 135

(37), 83 (40). Elem. Anal. Calcd for C₁₉H₃₄O₃Si₂C 62.24,

H 9.35 found: C 62.54, H 9.64.

6.5.6. Epoxidation of 22b. To a solution of m-cpba

(100 mg, 0.57 mmol, 1 equiv.), in CH₂Cl₂(6 mL) at

220 8C was added 22b (200 mg, 0.57 mmol, 1 equiv.).

After 6 h the solvent was evaporated and the solid was taken

back in pentane. The solution was ﬁltrated and concentrated

before chromatography (SiO₂, AcOEt/PE: 5:95) to give

78 mg of 37 and 27 mg of 36. (36) TLC R_f0.4. (AcOEt/PE,

5:95, KMnO₄). ¹H NMR (CDCl₃): d 7.56 (m, 2H), 7.35 (m,

3H), 4.10 (dd, 1H, J¼4.9, 4.7 Hz), 3.15 (m, 1H, J¼4.1 Hz),

3.11 (m, 1H, J¼4.1 Hz), 2.03 (m, 1H, J¼15.3, 7.3, 2.8 Hz),

1.94 (m, 1H, J¼15.3, 6 Hz), 1.84 (d, 1H, J¼4.7 Hz), 1.49

(ddd, 2H, J¼7.3, 6, 4.9 Hz), 0.88 (s, 9H), 0.44 and 0.41 (s,

3H), 0.03 and 20.03 (s, 3H). ¹³C NMR (CDCl₃): d¼139.01,

134.3, 129.34, 128.21, 67.53, 54.3, 52.65, 32.95, 28.00,

26.61, 20.93, 18.69, 21.63, 21.39, 23.86, 23.96.

MS(FAB): 385, 361, 345, 305, 231, 209, 135 (100).

HRMS: Calcd for C₂₀H₃₃O₂Si₂[M2H]^þ: 361.201912

found: M 361.201613. (37) TLC R_f0.64. (AcOEt/PE,

5:95, KMnO₄). ¹H NMR (CDCl₃): d 7.59 (m, 2H), 7.38 (m,

3H), 5.64 (m, 2H, J¼10.5, 7.5, 2.3 Hz), 4.09 (m, 2H), 1.77

(m, 2H), 1.62 (m, 2H), 0.88 (s, 9H), 0.395 and 0.392 (s, 3H),

0.05 (s, 6H). ¹³C NMR (CDCl₃): d¼138.75, 133.91, 132.93,

131.92, 129.89, 128.17, 66.55, 66.18, 29.07, 28.79, 26.25,

20.61, 20.65, 24.23, 24.24. MS(FAB): 385, 361, 345,

231, 209, 193, 147, 135 (100). HRMS: Calcd for

C₂₀H₃₃O₂Si₂(M2H): 361.201912 found: M 361.203290.

6.5.9. (1R,2R,3R,4R)-2-Dimethylphenylsilylcyclo-hexa-

1,3,4-triol (41). To a vigorously stirred solution (pink

colored) of water (3 mL) and K₂OsO₄.2H₂O (,8 mg,

2 mol%) was added NMO·H₂O (261 mg, 1.7 equiv.). The

solution turned yellow. To this mixture was added a solution

of the cyclohexene (260 mg, 1.12 mmol, 1 equiv.) in THF

(3 mL). The solution turned brown. After 8 h at rt, NaHSO₃

(100 mg) and magnesol (100 mg) were added to the

resulting yellow solution. After stirring for 30 min at rt,

the pH was adjusted to 1 with H₂SO₄and the reaction

mixture was ﬁltered of Celite. The magnesol was washed

twice with water and twice AcOEt. The organic phase was

separated and the aqueous phase extracted with AcOEt. The

combined organic phases were dried over MgSO₄and

concentrated in vacuo. Flash chromatography (SiO₂:

AcOEt) gave the triol as a colorless viscous oil. Traces of

solvent were removed by freeze-pump-thaw cycles. The

solid mixture was then triturated in hexane to obtain the triol

41 as a white solid in 80% yield (93% ee by HPLC). Mp

102 8C. [a]²_D³¼262.7 (c¼0.38 in CH₂Cl₂). TLC R_f0.35

6.5.7. (1S,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-cyclo-

hex-2-enol (39). To

a suspension of 38 (100 mg,

0.4 mmol, 1 equiv.) in CH₂Cl₂(2 mL) was added 22b

(138 mg, 0.4 mmol, 1 equiv.) in solution in CH₂Cl₂(1 mL).

After 1 h, the solvent was evaporated and the mixture was

taken back in pentane, the precipitate was ﬁltrated and the

solvent evaporated. Chromatography (SiO₂, AcOEt/PE:

25:75) to give 39²⁶(55 mg, 60% yield) TLC R_f0.45

(AcOEt/PE, 25:75, KMnO₄). ¹H NMR (CDCl₃): d 5.71

(pseudo q, 2H, J¼10.5, 4.8 Hz), 4.26 (m, 2H, J¼6.2,

1.6 Hz), 2.12 and 1.99 (m, 1H, J¼12.1, 4.8, 1.3 Hz), 1.59

(broad s, 1H), 1.49 (m, 2H, J¼12.9, 10.7, 8.3, 1.6 Hz), 0.89

(s, 9H), 0.07 (s, 6H). ¹³C NMR (CDCl₃): d¼134.2, 132.1,

67.4, 66.9, 31.4, 31.3, 26.2, 18.6, 24.3.

1

(AcOEt, KMnO₄). H NMR (CDCl₃): d 7.2–7.7 (m, 5H),

3.97 (m, 1H), 3.9 (dd, 1H, J¼11.3, 2.7 Hz), 3.82 (m, 1H),

1.82–1.96 (m, 1H), 1.6–1.77 (m, 2H), 1.49 (dd, 1H,

J¼11.3, 2.8 Hz), 1.3–1.41 (m, 1H), 0.389 and 0.385 (s, 3H).

¹³C NMR (CDCl₃): d 141.4, 135.5, 129.5, 128.5, 71.4, 71.2,

69.9, 33.6, 29.1, 27.1, 21.4, 22.2. IR (ﬁlm) n_maxcm²¹

3547, 3427, 3069, 3023, 2960, 2939, 2897, 1241, 1185,

1069. MS(CI): 417 (89), 399 (10), 265 (100), 247 (16), 151

(24). Elem. Anal. Calcd for C₁₄H₂₂O₃Si C 63.12, H 8.32

found: C 63.01, H 8.34.

6.5.8. (1R,2R,3R,4R)-4-(tert-Butyl-dimethylsilanyl-oxy)-

3-(dimethyl-phenyl-silanyl)-cyclopentane-1,2-diol (40).

To a vigorously stirred solution of water (2.5 mL) and

K₂OsO₄.2H₂O (,8 mg, 2.5 mol%) was added NMO·H₂O

(199 mg, 1.7 equiv.). The solution turned yellow. To this

mixture was added a solution of 22a (287 mg, 0.86 mmol,

1 equiv.) in THF (2.5 mL). The solution turned brown. After

8 h at rt, NaHSO₃(100 mg) and magnesol (100 mg) were

added to the resulting yellow solution. After stirring for

30 min at rt, the pH was adjusted to 1 with H₂SO₄and the

reaction mixture was ﬁltered of Celite. The magnesol was

washed twice with water and twice AcOEt. The organic

phase was separated and the aqueous phase extracted with

AcOEt. The combined organic phases were dried over

MgSO₄and concentrated in vacuo. Flash chromatography

(SiO₂, PE/AcOEt: 8:2) gave a colorless viscous oil. Traces

of solvent were removed and the solid mixture was then

triturated in hexane to obtain the diol 40 as a white solid

6.5.10. Chemical correlation from (1R,2R,3R,3R)-2-

dimethylphenylsilyl-cyclohexa-1,3,4-triol: synthesis of

(3aR,7aS)-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-benzo-

dioxole (42). To a solution of 41 (140 mg, 0.53 mmol,

1 equiv.) and dimethoxypropane (97 mL, 1.5 equiv.) in

CH₂Cl₂(5 mL) was added PTSA·H₂O (cat.). GC analysis

indicated completion of the reaction after 10 min at rt. A

solution of NaHCO₃sat was added and the organic layer was

separated. The aqueous phase was extracted with CH₂Cl₂.

The combined organic phases were dried over MgSO₄and

concentrated under reduced pressure to give the crude ketal

in 93% yield (99% pure by GC, 1% of the cis-

isopropylidene ketal was identiﬁed by GC/GC-MS). The

product was dissolved in THF (5 mL) and NaH (60%

dispersion in mineral oil, 25 mg, 1.3 equiv.) was added. The

reaction mixture was stirred for 5 h at 55 8C. Water and Et₂0

were added and the organic phase was separated. The

7342

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

aqueous phase was extracted with Et₂O. The combined

organic layers were dried over MgSO₄and concentrated in

vacuo. Flash chromatography (SiO₂: hexane 90:10 Et₂O)

gave the cyclohexene 42 in 82% yield (91% ee by GC on the

crude after chromatography). [a]²_D³¼þ17.5 (c¼0.68 in

CH₂Cl₂). TLC R_f0.35 (hexane/Et₂O, 9:1 KMnO₄¹H

NMR (CDCl₃): d 5.92 (dt, 1H, J¼10.1, 3.6 Hz), 5.71 (dm,

1H, J¼10.1 Hz), 4.5 (m, 1H), 4.27 (ddd, 1H, J¼6, 6,

3.8 Hz), 1.7–2.3 (m, 4H), 1.42 (s, 3H), 1.37 (s, 3H). ¹³C

NMR (CDCl₃): d 131.2, 125.4, 108.3, 73.1, 71.4, 28.1, 26.4,

25.5, 20.8. MS(EI, 70 eV): 233 (28) [M2acetone], 171 (14),

139 (54), 137 (100), 135 (76).

10.2 Hz), 5.03 (dd, 1H, J¼10.2, 1.9 Hz), 4.89 (dd, 1H,

J¼17.1, 1.9 Hz), 3.96 (m, 3H), 2.00 (s, 1H), 1.93 (dd, 1H,

J¼10.5, 2.4 Hz), 1.18 (s, 9H), 0.39 and 0.34 (s, 3H). ¹³C

NMR (CDCl₃): d 178.9, 137.8, 134.4, 134.2, 129.5, 128.1,

116.1, 69.9, 69.1, 39.3, 39.1, 27.5, 23.3, 23.7. IR (ﬁlm)

n

_maxcm²¹3491, 3071, 2961, 1730, 1625, 1481, 1428, 1399,

1284, 1256, 1160, 815, 734, 700. MS(CI): 319 (4) [M2H]^þ,

209 (10), 177 (46), 175 (72), 168 (54), 159 (100), 137 (53),

135 (94), 115 (38), 85 (31), 75 (86), 67 (88), 57 (61).

HRMS: Calcd for C₁₈H₂₇O₃Si [M2H]^þ319.172948 found:

M 319.173362.

6.5.13. (2R,3S)-2,2-Dimethyl-propionic acid 2-(tert-

butyl-dimethyl-silanyloxy)-3-(dimethyl-phenyl-silanyl)-

pent-4-enyl ester (46a). Following the typical procedure

C. The reaction was carried out on 1.5 g of 45 (4.7 mmol).

Flash chromatography (SiO₂, CH₂Cl₂/PE: 1:4) gave 1.28 g

of colorless oil (63% yield). [a]²_D³¼20.5 (c¼0.5 in CHCl₃).

TLC R_f0.73 (CH₂Cl₂/PE: 1:4, KMnO₄). ¹H NMR (CDCl₃):

d 7.84 (m, 2H), 7.34 (m, 3H), 5.88 (ddd, 1H, J¼17.1, 10.5,

10.2 Hz), 4.99 (dd, 1H, J¼10.2, 2.2 Hz), 4.80 (dd, 1H,

³J(H,H)¼17.1, 2.2 Hz), 4.00 (m, 2H), 3.87 (m, 1H), 2.09

(dd, 1H, J¼10.5, 2.4 Hz), 1.18 (s, 9H), 0.87 (s, 9H), 0.36 (s,

3H), 0.31 (s, 3H), 0.04 (s, 3H), 20.01 (s, 3H). ¹³C NMR

(CDCl₃): d 178.5, 138.3, 135.1, 134.4, 129.4, 128.1, 115.9,

70.8, 66.9, 39.7, 39.1, 27.6, 26.3, 18.5, 22.8, 23.5, 23.7,

23.8. IR (ﬁlm) n_maxcm²¹3072, 2958, 2858, 1734, 1480,

1397, 1362, 1255, 1150, 1004, 902, 835, 700. MS(CI): 419

(21) [M2Me]þ, 377 (67), 333 (21), 319 (60), 275 (25), 233

(51), 199 (47), 159 (100), 135 (47), 67 (60). HRMS: Calcd

6.5.11. 2,2-Dimethyl-propionic acid 2-oxo-ethyl ester

(43). (þ/2)-Solketal pyvaloate. Pyvaloyl chloride

(44.7 mL, 363 mmol, 1 equiv.) was added dropwise to a

gently agitated solution of solketal (48 g, 363 mmol,

1 equiv.) and pyridine (32.3 mL, 399 mmol, 1.1 equiv.) in

CH₂Cl₂(363 mL) at 210 8C. After standing two days at

room temperature the solution was washed thoroughly twice

with 30 mL of water and dried with MgSO₄. The CH₂Cl₂

was distilled off under normal pressure at the lowest

possible bath temperature. The residue was fractionally

distillated in vacuo (135–138 8C/60–80 mm Hg) to yield

1

65.7 g (83%) as a colourless oil. H NMR (CDCl₃): d 4.3

(m, 1H), 4.15 (dd, 1H, J¼11.5, 4.6 Hz), 4.11 (dd, 1H,

J¼11.5, 5.38 Hz), 4.06 (dd, 1H, J¼8.3, 6.4 Hz), 3.76 (dd,

1H, J¼8.3, 6.1 Hz), 1.43 (s, 3H), 1.36 (s, 3H), 1.21 (s, 9H).

1-Pivaloyloxypropane-2; 3-diol. To a solution of (þ/2)-

solketal pyvaloate (65 g, 300 mmol, 1 equiv.) in THF (250

mL) was added a solution of HCl 2 N (75 mL). The mixture

was then stirred overnight. After the reaction mixture was

saturated with NaCl, the products were extracted with

AcOEt (£4) and the organic layer was dried over MgSO₄to

give 52 g (98%) of 1-pivaloyloxypropane-2,3-diol²⁵as

for C₂₃H₃₉O₃Si₂[M2Me]^þ419.243777 found:

M

419.243722.

6.5.14. (2R,3S)-2,2-Dimethyl-propionic acid 3-(dimethyl-

phenyl-silanyl)-2-triisopropylsilanyloxy-pent-4-enyl

ester (46b). To a solution of TiPSCl (2 mL, 9.36 mmol,

1.5 equiv.) in DMF (6 mL) was added imidazole (1.7 g,

25 mmol, 4 equiv.). The reaction mixture was heated to

60 8C for 1:2 h before to add 45 (2 g, 6.24 mmol, 1 equiv.).

The reaction was monitored by GC. After 48 h NH₄Clsat

(5 mL) were added. The aqueous phase was extracted with

pentane (3£5 mL), the combined organic phases were dried

over MgSO₄and concentrated in vacuo. Flash chromato-

graphy (SiO₂, CH₂Cl₂/PE, 1:4) gave 1.77 g of 46b as a

colorless oil (59% yield). [a]²_D³¼18 (c¼1.11 in CHCl₃).

TLC R_f0.27 (CH₂Cl₂/PE: 1:4, KMnO₄). ¹H NMR (CDCl₃):

d 7.48 (m, 2H), 7.33 (m, 3H), 5.78 (ddd, 1H, J¼17.1, 10.5,

10.5 Hz), 5.11 (ABX system, ddd, 1H, J¼6.2, 6.2, 4.5 Hz),

5.01 (dd, 1H, J¼10.5, 2.1 Hz), 4.88 (dd, 1H, J¼17.1,

2.1 Hz), 3.51 and 3.48 (ABX system, 2dd, 2H, J¼10,

6.2 Hz), 2.28 (dd, 1H, J¼10.5, 4.5 Hz), 1.1 (s, 9H), 0.985 (s,

21H), 0.323 and 0.318 (2s, 6H). ¹³C NMR (CDCl₃): d 177.9,

137.8, 134.8, 134.3, 129.5, 128.1, 116.2, 73.7, 64.3, 39.3,

36.8, 27.7, 18.4, 12.3, 23.1, 23.6. IR (ﬁlm) n_maxcm²¹

3070, 2958, 2866, 1730, 1626, 1461, 1427, 1279, 1249,

1157, 1113, 1014, 882, 812, 733. MS(CI): 433 (95)

[M2(CH₃)₂CH]^þ, 375 (10), 345 (9), 289 (14), 285 (18),

215 (100), 201 (31), 197 (20), 159 (32), 135 (16), 111 (18).

HRMS: Calcd for C₂₄H₄₁O₃Si₂[M2iPr]^þ433.259427

found: M 433.258928.

1

colourless oil. H NMR (CDCl₃): d 4.44 (broad s, 2H),

4.12 (m, 2H), 3.91 (m, 1H), 3.68 (dd, 1H, J¼11.5, 3.3 Hz),

3.57 (dd, 1H, J¼11.5, 6.1 Hz), 1.19 (s, 9H). (43) To a

solution of 1-pivaloyloxypropane-2,3-diol (10 g,

56.7 mmol, 1 equiv.) in CH₂Cl₂(85 mL) was added a

solution of sodium periodate (13.3 g, 62.4 mmol, 1.1 equiv.)

in water (85 mL). This biphasic solution was stirred for

3–4 h. The organic layer was separated and concentrated

to give an oil which was distilled (87 8C/65 mm Hg). The

aldehyde was obtained as an colorless oil (8.9 g, 71%

1

yield). H NMR (CDCl₃): d 9.59 (s, 1H), 4.65 (s, 2H), 1.27

(s, 9H). ¹³C NMR (CDCl₃): d 195.9, 177.9, 68.5, 38.7, 27.1.

6.5.12. (2R,3S)-2,2-Dimethyl-propionic acid 3-(dimethyl-

ester

phenyl-silanyl)-2-hydroxy-pent-4-enyl

(45).

Following the typical procedure A. To a solution of

allyldimethylphenylsilane (2.6 g, 15 mmol, 1.1 equiv.) in

THF (33 mL) at rt were added 2.3 M n-BuLi (6.5 mL,

15 mmol, 1.1 equiv.) dropwise over 10 min. After 20 min,

the yellow solution was transferred via canula over 10 min

to

a

suspension of (R,R)-TiClCpTADDOL (10 g,

15.6 mmol, 1.15 equiv.) in THF (40 mL) at 278 8C. After

30 min, 43 (2 g, 13.5 mmol, 1 equiv.) was added. Chroma-

tography (SiO₂, CH₂Cl₂/PE: 2:3) gave 45 as a colorless oil:

2.44 g (56% yield). [a]²_D³¼21.6 (c¼1 in CHCl₃). TLC R_f

1

0.41 (CH₂Cl₂/PE, 2:3, KMnO₄). H NMR (CDCl₃): d 7.55

6.5.15. (2R,3S)-3-(Dimethyl-phenyl-silanyl)-2-triiso-

propyl-silanyloxy-pent-4-en-1-ol (47). To a solution of

(m, 2H,), 7.36 (m, 3H), 5.89 (ddd, 1H, J¼17.1, 10.5,

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

7343

46b (410 mg, 0.85 mmol, 1 equiv.) in CH₂Cl₂(5 mL) was

added DIBAL 1.5 M in toluene (1.15 mL, 2 equiv.) after

stirring for 1 h at 278 8C the reaction was quenched with

methanol (1 mL) and 2 mL of a solution of NH₄Clsat were

added. The mixture was stirred vigorously at rt for 2 h and

the whole was extracted with AcOEt (2£5 mL). The

combined organic extracts were washed with brine (5 mL)

and dried over MgSO₄. Filtration and evaporation in vacuo

furnished the crude product, which was puriﬁed by ﬂash

chromatography (SiO₂: CH₂Cl₂/PE: 1:4) to give 246 mg of

colorless oil (73% yield). [a]²_D³¼11.4 (c¼1.02 in CHCl₃).

TLC R_f0.53 (CH₂Cl₂/PE, 2:3, KMnO₄). ¹H NMR (CDCl₃):

d 7.56 (m, 2H), 7.35 (m, 3H), 5.92 (ddd, 1H, J¼17.1, 10.2,

9.9 Hz), 4.96 (dd, 1H, J¼10.2, 2.1 Hz), 4.82 (dd, 1H,

J¼17.1, 2.1 Hz), 3.79 (ABX system, ddd, 1H, J¼10, 3.9,

2.4 Hz), 3.46 and 3.44 (ABX system, 2dd, 2H, J¼14, 10,

2.4 Hz), 2.62 (broad s, 1H), 2.00 (dd, 1H, J¼9.9, 3.9 Hz),

1.01 and 1.00 (2s, total 21H), 0.39 and 0.33 (s, 3H). ¹³C

NMR (CDCl₃): d 138.3, 135.3, 134.4, 129.3, 128.0, 114.7,

71.8, 68.1, 38.5, 18.5, 12.4, 23.0, 23.7. IR (ﬁlm) n_max

cm²¹3575, 3069, 2943, 2866, 1624, 1463, 1427, 1247,

1113, 1100, 1017, 882, 807. MS(CI): 391(3) [M2H]^þ, 376

(49), 375 (100) [M2OH²]^þ, 315 (20), 307 (15), 239 (57),

231 (65), 205 (58), 197 (65), 157 (15), 135 (68), 67 (100).

HRMS: Calcd for C₂₂H₃₉O₂Si₂[M2H]^þ391.248863

found: M 391.252510.

overnight. Concentration in vacuo followed by ﬂash

chromatography (SiO₂: hexane) gave 82 mg of product

(93% yield). TLC R_f0.49 (hexane, KMnO₄). ¹H NMR

(CDCl₃): d 7.48 (m, 2H), 7.34 (m, 3H), 6.19 (dd, 1H, J¼2.7,

2.4 Hz), 4.76 (dd, 1H, J¼2.7, 2.7 Hz), 4.52 (ddd, 1H, J¼7.2,

6.3, 4.8 Hz), 3.63 (dd, 1H, J¼10.2, 6.3 Hz), 3.49 (dd, 1H,

J¼10.2, 4.8 Hz), 2.21 (ddd, 1H, J¼7.2, 2.7, 2.4 Hz), 1.01

and 1.00 (2s, total of 21H), 0.29 and 0.28 (2s, total of 6H).

¹³C NMR (CDCl₃): d 137.8, 134.3, 134.1, 129.7, 128.4,

97.8, 83.1, 64.9, 23.5, 18.4, 12.4, 20.9, 22.6. IR (ﬁlm) n_max

cm²¹3069, 2943, 2866, 1762, 1691, 1463, 1427, 1251,

1113, 1063, 1014, 882. MS(CI): 390 [M]^þ(4), 375 (5), 347

(14), 265 (39), 180 (98), 169 (35), 157 (75), 137 (43), 135

(63), 123 (100), 75 (17). HRMS: Calcd for 391.248863

found: M 391.247701.

Acknowledgements

We warmly thank the FNRS (Belgium) and the Ministry of

Research (France) for PhD fellowships to J.M.A. and L.dF.

`

These studies were supported by grants from the Ministere

de l’Education et de la Recherche, Communaute franc¸aise

´

de Belgique (action concertee), the Universite catholique de

Louvain, the Conseil Regional d’Aquitaine and the

´

Universite Bordeaux I. We are also indebted to Prof. E. de

Hoffmann and Prof. J.-L. Habib for the mass spectra, Prof.

Flammang for the HRMS and Dr. Roland Touillaux for the

meticulous measurement and recording of high-ﬁeld NMR

spectra.

6.5.16. (2R,3S)-3-(Dimethyl-phenyl-silanyl)-2-triiso-pro-

pylsilanyloxy-1-vinyloxy-pent-4-en-1-yl ether (48). To a

solution of 47 (328 mg, 408 mmol, 1 equiv.) in ethyl–vinyl

ether (3 mL) was added mercury(II) acetate (143 mg,

448 mmol, 1.1 equiv.) and the resulting mixture was heated

at reﬂux for 48 h. The ethyl-vinyl ether was then remove

under reduced pressure. The resulting oil was taken back in

pentane and the organic phase was washed with brine, dried

over MgSO₄and concentrated in vacuo. Flash chromato-

graphy (SiO₂, CH₂Cl₂/PE: 1:9) gave 240 mg of the

vinylether 48 (67% yield). [a]²_D³¼þ12 (c¼0.6 in CDCl₃).

TLC R_f0.9 (CH₂Cl₂/PE, 1:4, KMnO₄). ¹H NMR (CDCl₃): d

7.68 (m, 2H), 7.51 (m, 3H), 6.38 (dd, 1H, J¼13.8, 6.3 Hz),

6.03 (ddd, 1H, J¼17.1, 10.5, 10.2 Hz), 5.15 (dd, 1H,

J¼10.2, 2.4 Hz), 5.01 (dd, 1H, J¼17.1, 2.4 Hz), 4.39 (dd,

1H, J¼13.8, 1.5 Hz), 4.05 (dd, 1H, J¼6.3, 1.5 Hz), 3.97

(ddd, 1H, J¼6.6, 6.3, 2.4 Hz), 3.83 (dd, 1H, J¼10.1,

6.6 Hz), 3.71 (dd, 1H, J¼10.1, 6.3 Hz), 2.29 (dd, 1H,

J¼10.5, 2.4 Hz), 1.17 and 1.16 (2s, total of 21H), 0.52 and

0.47 (s, 3H). ¹³C NMR (CDCl₃): d 152.5, 137.6, 134.4,

134.2, 128.9, 127.8, 115.4, 87.4, 80.9, 65.0, 37.3, 17.9, 11.8,

23.8, 24.5. IR (ﬁlm) n_maxcm²¹3070, 2943, 2866, 1627,

1463, 1427, 1249, 1186, 1114, 1052, 1004, 882, 812, 699.

MS(CI): 391(5) [M2CHvCH₂]^þ, 377 (55), 375 (100), 353

(10), 315 (20), 241 (20), 239 (55), 231 (61), 205 (57), 197

(53), 157 (15), 135 (55), 67 (85). HRMS: Calcd for

C₂₂H₃₉OSi₂[M2CH₂vCH–O]^þ375.253948 found: M

375.252969.

References and notes

1. Adam, J.-M.; Ghosez, L.; Houk, K. N. Angew. Chem., Int. Ed.

1999, 38, 2728–2730.

2. For reviews see: (a) Grubbs, R. H.; Chang, S. Tetrahedron

1998, 54, 4413. (b) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000,

39, 3012–3043.

3. (a) Fu¨rstner, A.; Langemann, K. J. Am. Chem. Soc. 1997, 119,

9130–9136. (b) Cossy, J.; Bauer, D.; Bellosta, V. Tetrahedron

Lett. 1999, 40, 4187–4188. (c) Scholl, M.; Grubbs, R. H.

Tetrahedron Lett. 1999, 40, 1425–1428. (d) Ahmed, M.;

Barrett, A. G. M.; Beall, J. C.; Braddock, D. C.; Flack, K.;

Gibson, V. C.; Procopriou, P. A.; Slater, M. M. Tetrahedron

1999, 55, 3219–3232. (e) Mulzer, J.; Hanbauer, M.

Tetrahedron Lett. 2000, 41, 33–36. (f) Ramachandran, P. V.;

Reddy, M. R. V.; Brown, H. C. Tetrahedron Lett. 2000, 41,

583–586. (g) Cossy, J.; Willis, C.; Bellosta, V.; Bouzbouz, S.

Synlett 2000, 10, 1461–1463. (h) Landais, Y.; Surange, S. S.

Tetrahedron Lett. 2001, 42, 581–584. (i) Felpin, F. X.; Girard,

S.; Vo-Than, G.; Robins, R. J.; Villieras, J.; Lebreton, J. J. Org.

Chem. 2001, 66, 6305–6312. (j) Cossy, J.; Willis, C.; Bellosta,

V.; Bouzbouz, S. J. Org. Chem. 2002, 67, 1982–1992.

(k) Bouzbouz, S.; Cossy, J. Tetrahedron. Lett. 2003, 44,

4471–4473. (l) Bouzbouz, S.; Cossy, J. Org. Lett. 2003, 5,

3029–3031. (m) Marco, J. A.; Carda, M.; Rodriguez, S.;

Castillo, E.; Kneeteman, M. N. Tetrahedron 2003, 59,

4085–4101.

6.5.17. (3R,4S)-4-(Dimethyl-phenyl-silanyl)-3-triiso-pro-

pylsilanyloxy-3,4-dihydro-2H-pyran (49). To a solution

of 48 (100 mg, 0.229 mmol, 1 equiv.) in CH₂Cl₂(20 mL)

was added 23 (49 mg, 0.057 mmol, 0.25 equiv.) in solution

in CH₂Cl₂(1 mL). The mixture was heated 4 h at reﬂux until

disappearance of the starting compound. The ruthenium

catalyst was then oxidize by stirring the mixture at open air

4. (a) Heo, J.-N.; Micaizio, G. C.; Roush, W. R. Org. Lett. 2003,

5, 1693–1696. (b) Heo, J.-N.; Holson, E. B.; Roush, W. R.

Org. Lett. 2003, 5, 1697–1700.

7344

J.-M. Adam et al. / Tetrahedron 60 (2004) 7325–7344

5. Preliminary report: de Fays, L.; Adam, J.-M.; Ghosez, L.

16. (a) For catalyst 23 see Ref. 13. (b) Sanford, M. S.; Love, J. A.;

Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543–6554.

17. (a) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J.;

Nolan, S. P. J. Org. Chem. 2000, 65, 2204–2207.

(b) Kinderman, S. S.; van Maarseveen, J. H.; Schoemaker,

H. E.; Hiemstra, H.; Rutjes, F. P. J. T. Org. Lett. 2001, 3,

2045–2048. (c) Bourgeois, D.; Pancrazi, A.; Nolan, S. P.;

Prunet, J. J. Organomet. Chem. 2002, 643-644, 247–252.

18. For synthesis of (4S,5S)-2,2-dimethyl-5-vinyl-[1,3]-

dio-xolane-4-carbaldehyde 27 see: Moon, H. R.; Choi, W. J.;

Kim, H. O.; Jeong, L. S. Tetrahedron: Asymmetry 2002, 13,

1189–1193.

Tetrahedron Lett. 2003, 44, 7197–7199.

6. Crowe, W. E.; Golberg, D. R.; Zhang, Z. J. Tetrahedron Lett.

1996, 37, 2117–2120.

7. (a) Brummer, O.; Rucket, A.; Blechert, S. Chem. Eur. J 1997,

3, 441–446. (b) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.;

Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360–11370,

and references cited therein.

8. Ulman, M.; Grubbs, R. H. Organometallics 1998, 17,

2484–2489.

9. Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc.

1997, 119, 3887–3897.

´

10. Adam, J.-M. PhD Dissertation, Universite catholique de

Louvain, 2000.

19. White, J.-M. Aust. J. Chem. 1995, 48, 1227–1252.

20. Ethoxycarbonylmethylation: (a) Reissig, H.-U.; Reichelt, I.;

Kunz, T. Org. Synth. 1993, 71, 189–199. (b) Angelaud, R.;

Landais, Y.; Parra-Rapado, L. Tetrahedron Lett. 1997, 38,

8845–8848.

11. For chromium-catalyzed reactions see: Fu¨rstner, A. Chem.

Rev. 1999, 99, 991–1045.

12. (a) Ulman, M.; Grubbs, R. H. J. Org. Chem. 1999, 64,

7202–7207. (b) Kirkland, T. A.; Lynn, D. M.; Grubbs, R. H.

J. Org. Chem. 1999, 63, 9904–9909.

21. Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron 1992, 49,

423–438.

13. Scholl, M.; Ding, S.; Woo Lee, C.; Grubbs, R. H. Org. Lett.

1999, 1, 953–956.

22. Wang, Z.-M.; Kakiuchi, K.; Sharpless, K. B. J. Org. Chem.

1994, 59, 6895–6897.

14. Synthesis of 3-butenal: (a) Crimmins, M. T.; Kirincich, S. T.;

Wells, A. J.; Choy, A. L. Synth. Commun. 1998, 28,

3675–3679. Synthesis of 5-hexenal: (b) Ikeda, T.; Yue, S.;

Hutchinson, C. R. J. Org. Chem. 1985, 50, 5193–5199.

Synthesis of 6-heptenal: (c) Taylor, R. E.; Galvin, G. M.;

Hilﬁker, K. A.; Chen, Y. J. Org. Chem. 1998, 63, 9580–9583.

15. (a) Duthaler, R. O.; Hafner, A. Chem Rev. 1992, 92, 807–832.

(b) Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-

Streit, P.; Schwarzenbach, F. J. Am. Chem. Soc. 1992, 114,

2321–2336.

23. Haasnoot, C. A. G.; De Leeuw, F. A. A. M.; Altona, C.

Tetrahedron 1980, 36, 2783–2792.

24. Kashihara, H.; Suemune, H.; Kawahara, K.; Sakai, K. J. Chem.

Soc., Perkin Trans. 1 1990, 1663–1667.

25. Balint, J.; Egri, G.; Kolbert, A.; Dianoczky, C.; Fogassy, E.;

Novak, L.; Poppe, L. Tetrahedron: Asymmetry 1999, 10,

4017–4028.

26. Arjona, O.; de Dios, A.; Plumet, J.; Saez, B. J. Org. Chem.

1995, 60, 4932–4935.

Article Doi

Asymmetric synthesis of cyclic β-hydroxyallylsilanes via sequential allyltitanation-ring closing metathesis

DOI: 10.1016/j.tet.2004.05.058

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tet.2004.05.058

Full text of DOI:10.1016/j.tet.2004.05.058

Products guided by the article

R&D Labs maybe for 757748-49-5

Relevant to this article

Hot Product