Nazarov reactions intercepted by (4 + 3) cycloadditions with oxygen-substituted dienes

Article abstract of DOI:10.1021/acs.joc.5b00914

The oxyallyl cation intermediate from the Lewis acid mediated Nazarov reaction of an allenyl vinyl ketone was intercepted by acyclic, 2-silyloxy-substituted butadienes by highly regioselective (4 + 3) cycloadditions. Stereoselectivity was often modest, bu

Full text of DOI:10.1021/acs.joc.5b00914

Article
pubs.acs.org/joc
Nazarov Reactions Intercepted by (4 + 3) Cycloadditions with
Oxygen-Substituted Dienes
Franco̧ is M. LeFort, Vinayak Mishra, Graham D. Dexter, Timothy D. R. Morgan, and D. Jean Burnell*
Department of Chemistry, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada
S
* Supporting Information
ABSTRACT: The oxyallyl cation intermediate from the Lewis acid
mediated Nazarov reaction of an allenyl vinyl ketone was
intercepted by acyclic, 2-silyloxy-substituted butadienes by highly
regioselective (4 + 3) cycloadditions. Stereoselectivity was often
modest, but in some instances steric interactions were responsible
for high selectivity. The results are consistent with concerted (4 + 3)
cycloadditions. In many instances, the (4 + 3) products were
susceptible to fragmentation or rearrangement in the presence of the Lewis acid.
Although a strong π-donor on the diene would be expected
INTRODUCTION
■
to control the regioselectivity of cycloaddition to the oxyallyl
cation 2, how electron donation would influence the (3 + 2)
versus (4 + 3) selectivity was not known. A previous attempt to
intercept the Nazarov reaction of AVK 1 with Danishefsky’s
diene had given only the product of Diels−Alder addition to
the AVK.6 Thus, butadiene derivatives substituted by only one
oxygen function (at the 2-position) were evaluated for trapping
the Nazarov reaction of an AVK. The results reported here
provide valuable insights for synthesis and may contribute to a
better mechanistic understanding of these complex cyclizations.
The past decade has seen considerable development of the
“interrupted” version of the thermal Nazarov reaction,1 in
which the intermediate oxyallyl cation is intercepted by a
nucleophile or by further cyclization.2 Among the most
synthetically attractive modes of interception has been (4 +
3) cycloaddition.3,4 We have shown that allenyl vinyl ketones
(AVKs), e.g., 1, are well suited as substrates for interrupted
Nazarov reactions.5−8 While the cationic intermediates (e.g., 2)
from the reactions of AVKs did react readily with acyclic dienes
with a high degree of regio- and stereoselectivity, the products
were often mixtures from (4 + 3) and (3 + 2) cycloaddition
processes. For instance, products 3 and 4 in Scheme 1 were
RESULTS AND DISCUSSION
■
The Nazarov reaction of AVK 1 in the presence of 2-
[(trimethylsilyl)oxy]-1,3-butadiene9 (5) was mediated by BF3·
Et2O. The product arose regioselectively and with high facial
selectivity by a tandem Nazarov/(4 + 3) cycloaddition process,
but after purification on silica gel much of the material was
desilylated, and so both 6 and 7 were obtained (Scheme 2).
The products of the Nazarov reactions in the presence of
dienes 8 and 9 were also considerably desilylated. TLC analysis
of the crude reaction mixtures, before workup and chromatog-
raphy, indicated the presence of both the silyl enol ethers and
the ketones. Thus, some desilylation appeared to be occurring
under the reaction conditions. Nevertheless, the only Nazarov
products that were obtained had undergone (4 + 3)
cycloaddition with the diene, and the regioselectivity was
controlled completely by the silyloxy group. There were
notable differences between the results with dienes 8 and 9.
The yield of (4 + 3) products (10 + 11) from diene 8 was only
26%, but the stereoselectivity at the methyl-bearing stereo-
center was high. The methyl group (R1) was “down” as drawn
in Scheme 2,10 and compound 12 was also isolated. With diene
9 the combined yield of Nazarov product (13a,b + 14a,b) was
Scheme 1. Nazarov Reaction of AVK 1 in the Presence of
trans-Piperylene6
obtained in a ratio of 1:2.7 favoring the (3 + 2) product.
Isoprene and 2,3-dimethylbutadiene both intercepted the
oxyallyl cation 2 exclusively by (4 + 3) cycloaddition, although
the regioselectivity with isoprene was modest (2.8:1).6
Complete substitution of a terminus led to products that
were almost exclusively the result of (3 + 2) cycloaddition.6,8
Computational results indicated that the annular sp2 carbon on
the terminus of the π-system is the most electrophilic in oxyallyl
cation 2 (with the asterisk in Scheme 1),7 which was consistent
with the regioselectivity observed in the trapping reactions.
Received: April 23, 2015
© XXXX American Chemical Society
A
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Scheme 2. Tandem Nazarov/(4 + 3) Cycloadditions of AVK
1 in the Presence of Dienes 5, 8, and 9
Table 1. Products of the Tandem Nazarov/Cycloadditions of
AVK 1 in the Presence of Dienes 15−23
a
a
A 5:1 ratio of methyl epimers (13a,b); the major epimer (13a) is
b
shown. A 1:1.2 ratio of methyl epimers (14a,b); the major epimer
(14b) is shown.
95%, but the stereoselectivity was modest at the methyl-bearing
center. The methyl group (R2) in the major epimer 13a was
“up” as drawn in Scheme 2, but the hydrolyzed product had
almost equal amounts of the epimers 14a and 14b.
Desilylation or hydrolysis of the products from dienes 5, 8,
and 9 had presented problems with analysis, and so dienes 15−
23 with more robust TBS ether groups were prepared.11 BF3·
Et2O-mediated Nazarov reactions of AVK 1 were carried out in
the presence of these dienes (Table 1). The dienes themselves,
particularly those that were unsubstituted at C-1,12 degraded
quite rapidly under the reaction conditions. Cycloaddition
occurred exclusively onto the face of 2 opposite the phenyl
group, and the oxygen function controlled the regioselectivity.
The terminus to which the oxygen donated its electron density
bonded to the most electrophilic carbon of 2, but there were
two exceptional cases. In diene 20 the more electron-rich
terminus (C-1) was completely substituted, and this diene
trapped 2 by (3 + 2) cycloaddition to give 30a,b. With diene 22
it appeared that the cation-stabilizing ability of the phenyl
substituent competed with the oxygen function, and the (4 + 3)
product 32a,b was accompanied by a lesser amount of 33 with
the regiochemistry reversed.
Dienes 16 and 17, which bore substitution at C-4 in an E-
geometry, with AVK 1 gave (4 + 3) products 25 and 26 very
largely as one diastereomer. The structure of 25 was confirmed
by X-ray crystallography. This stereoselectivity mirrored the
selectivity that had been observed with the dienes without
oxygen functions.6,8 The high degree of stereoselectivity in the
reactions with 16 and 17 was in contrast with examples in the
literature4a,13,14 of modest stereoselectivity in the (4 + 3)
cycloadditions to oxyallyl cations. The yield of 25 was modest,
but it was accompanied by a greater amount of 12.15 It is
noteworthy that diene 18 gave the (4 + 3) product 28. Similar
dienes without the oxygen function had trapped 2 exclusively
by (3 + 2) cycloaddition,6,8 and, although the cycloadditions of
16 and 17 were highly stereoselective, 28 bore methyl groups in
both the “up” and “down” orientations.
Diene 19, just like diene 9, provided (4 + 3) products 29a,b
and 14a,b in a very high combined yield from AVK 1. However,
once again, desilylation was facile and the major epimer 14b
had its methyl group “down”. It is likely that the stereo-
selectivity of the cycloaddition was modest. Other C-1-
substituted dienes 21 and 22 gave (4 + 3) products 31a,b
and 32a,b with the epimeric substituents mainly “up”, and it
a
Reaction conditions: BF3·Et2O (1.1 equiv), diene (5 equiv), in
b
CH2Cl2, −78 °C, 5 min; chromatography over silica gel. Obtained as
a mixture of epimers (a, b) at the indicated carbon. The major epimer
is the one shown. The ratios of the epimers did not alter significantly
during purification. Yields were estimated. The product was obtained
in two fractions. The first fraction (33%) was 32a, and the second
c
(21%) was a 1:1.3 mixture of 32b and 33, respectively.
B
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was interesting that in the minor product 33 the phenyl group
was “down” as in 25 and 26. However, diene 23 with a bulkier
isopropyl substituent gave only 34, with the substituent
“down”. The structure of 34 was verified by X-ray
crystallography.
via (4 + 3) cycloaddition but with the regioselectivity reversed
to give 40a,b.
The appearance of 12 in the reactions of dienes 8 and 16
might be consistent with a stepwise mechanism for the (4 + 3)
cycloadditions. Compound 12 would be the product if the
reaction stopped after the formation of the first carbon−carbon
bond, i.e., a “homologous Mukaiyama” product for which there
is precedent when an oxyallyl cation is intercepted by an
oxygen-substituted alkene.6,16 However, similar compounds
have been produced by the acid-mediated opening of some (3
+ 2) products of unoxygenated dienes.8,17 Thus, some (4 + 3)
products from this study were treated briefly with BF3·Et2O at
rt. The results are summarized in Scheme 5. Compound 25,
AVK 1 and BF3·Et2O were added to a mixture of 2 equiv
1
each of 16 and 19. The H NMR spectrum of the crude
product revealed a ratio of 1:3.5:8:2, respectively, for the
trapped Nazarov products 25/12/29a/29b. Therefore,
although diene 19 gave a higher yield of tandem product
compared to diene 16, diene 19 reacted with the oxyallyl cation
2 only slightly more quickly than did diene 16. The implication
was that diene 35, with substituents on both termini, would be
subject roughly equally to the phenomena that controlled the
development of stereochemistry at both C-1 and C-4. The
result of trapping the Nazarov reaction of AVK 1 with 35 was
the formation of almost equal amounts of the (4 + 3) products
36, with both methyl groups “down”, and 37, with both methyl
groups “up” (Scheme 3).
Scheme 5. Room-Temperature Treatment of (4 + 3)
Cycloaddition Products with BF3·Et2O
Scheme 3. Nazarov Reaction of AVK 1 in the Presence of
Diene 35
AVKs 38 and 1 just differ in the position of the methyl
group, but computations have shown that the most electro-
philic carbon in the oxyallyl cation derived from 38 is on the
same carbon as in 2.7 Nevertheless, 38 is much less stable than
1, and lower yields were expected with 38. (As such, the yields
in Scheme 4 are over three steps: the oxidation of the alcohol to
Scheme 4. Nazarov Reactions of AVK 38 in the Presence of
Dienes 18 and 19
a
Obtained as a mixture of epimers (a, b) at the indicated carbon; the
major epimer (40a) is shown.
which had been initially obtained with 12, provided the ring-
opened compound 12 cleanly. Thus, the (4 + 3) product 25
has limited stability in the presence of the Lewis acid, and 12
might also have been derived from the (4 + 3) product rather
than from a competing stepwise process. Obviously, the
isolated yield of 25 from the original Nazarov/cycloaddition
tandem process might have been reduced significantly by a
the ketone, base-induced isomerization to the AVK, and the
tandem Nazarov/(4 + 3) cycloaddition.) Two reactions were
carried out using 38. Trapping its Nazarov reaction with diene
18 led to the (4 + 3) product 39, which was in accord with the
formation of 28. Diene 19, however, trapped the oxyallyl cation
C
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subsequent ring-opening reaction. The epimeric mixture of
29a,b gave the desilylated products 14a,b in very high yield, but
no ring-opened product was detected. The ratio of the epimers
was unaltered during desilylation, which suggested that
epimerization could not have been extensive under the
conditions of the initial experiments. Thus, the stereoselectivity
of the (4 + 3) cycloadditions of dienes 9 and 19 was indeed
modest, approximately 4:1. On the other hand, the isolated
yields of (4 + 3) cycloaddition products with dienes 9 and 19
were the highest of all the dienes. Compound 34 was also
desilylated without epimerization. Compounds 36 and 37 were
also of limited stability in the presence of BF3·Et2O. These
compounds gave mixtures of desilylated (but not epimerized)
compounds 42 and 45, ring-opened compounds 43 and 46, and
compounds with a rearranged, bicyclo[5.2.1]decenedione
framework 44 and 47. These rearrangement products would
have arisen by the same ring-opening process as the process
that produced 43 and 46 but followed by reclosure onto the
exocyclic double bond. This rearrangement is precedented,6,8
but these examples show that the reclosure takes place
stereoselectively forming the new chiral center with the methyl
“down”. In addition, these results affirm that even the
rearrangement proceeds without epimerization.
cycloadditions are concerted. The stereoselectivity and, in
one instance, the regioselectivity can be explained by invoking
an asynchronous transition state in which the shorter incipient
bond a is the one from the electron-rich terminus of the diene
to the most electrophilic carbon of the oxyallyl cation.
Diagrams of some representative transitions states are shown
in Figure 1. A concerted cycloaddition could take place via a
The mechanism of (4 + 3) cycloaddition has been the subject
of some debate.18 The formation of (4 + 3) products can only
take place with a diene in its s-cis conformation. A transition
state A (illustrated with AVK 1 and diene 16 in Scheme 6)
Figure 1. Representations of transition states for concerted but
asynchronous (4 + 3) cycloadditions: a is a shorter incipient bond
than b. D is a compact transition state for 2 with diene 16; E is an
extended transition state for 2 with diene 16; F is a compact transition
state for 2 with diene 19; G is an unfavored (compact) transition state
for the oxyallyl cation from 38 with diene 19.
Scheme 6. Reaction of AVK 1 with s-trans Diene 16
compact D or an extended transition state E, illustrated for the
concerted cycloaddition of 2 with diene 16. In this instance, the
energy of E must be lower than of D since the observed (4 + 3)
product was 25, and so it is suggested that the stereoselectivity
might be the result of a greater steric interaction between the
methyl groups in D than in E. (Computational data would be
required to corroborate this suggestion.) A steric interaction
between the methyl groups in either transition state might have
lowered the proportion of concerted (4 + 3) cycloaddition in
favor of a stepwise reaction that would have given compound
12. Note that the stereochemistry of the product 32 would have
been controlled by a similar methyl−phenyl interaction. The
oxyallyl cation 2 with diene 19 gave 29a,b with a small
stereochemical bias. In this instance, the methyl groups cannot
interact sterically, and the transition state energy for the (4 + 3)
cycloaddition would be lower, leading to the high yield of (4 +
3) products. In addition, the difference in the transition-state
energies between the compact and the extended geometries is
not large without a significant steric interaction between
substituents on the termini of the diene and on the α positions
of the oxyallyl cations. In fact, that 29a, with the methyl “up”,
was the slightly favored isomer indicates that in the absence of
significant steric interactions the compact transition state F is
slightly favored over the extended transition state. Dienes 21
and 22 reacted with stereoselectivities as with 19, but the result
with diene 23 might have reflected a hydrogen−isopropyl
interaction that was now significant at the transition state of the
(4 + 3) cycloaddition that led to 34. Why the methyl−methyl
interaction is more inhibiting in G than in D is due to the
asynchronous transition state, i.e., the methyls would be closer
in G than in D.
represents the initial carbon−carbon bond formation for a
stepwise process with a diene in its s-trans conformation. This
can only lead to an allylic cation B, but in order to cyclize to the
(4 + 3) cycloaddition product 25 the allylic cation would need
to isomerize to C.19 This isomerization would not be feasible
during the course of a 5 min reaction in an aprotic solvent at
−78 °C. On the other hand, 12 and products of (3 + 2)
cycloaddition could arise from B without isomerization. Thus,
unless the initial carbon−carbon bond-forming process was
reversible, reaction of the oxyallyl cation 2 with any diene in its
s-trans conformation could not lead to a (4 + 3) cycloaddition
product. Competitive reactions of s-trans dienes might be a
significant factor in the generally modest yields of (4 + 3)
cycloaddition products.
The most plausible reason why almost every diene in this
study, even diene 18 for which the s-trans conformation would
be much favored over the s-cis, gave a product derived from the
diene in its s-cis conformation is that these (4 + 3)
The trapping of 2 with diene 35 was a process in which the
methyl substituents on the diene would have acted in
D
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Melting points (uncorrected) were acquired using a Fisher-Johns
apparatus. Chemical shifts (δ) are reported in parts per million (ppm)
downfield from tetramethylsilane and are referenced to the solvent
peak (for CDCl3, 1H NMR: 7.26 ppm, 13C NMR: 77.16 ppm).
Positive-ion high-resolution mass spectra (HRMS) were obtained
using APCI or ESI on a TOF mass spectrometer. Infrared (IR) spectra
were recorded on an FT instrument. Samples were prepared as thin
opposition. The methyl group at C-1 of the diene would have
favored the compact transition state, but in this geometry the
methyl group at C-4 of the diene would have inhibited a (4 +
3) cycloaddition. On the other hand, the extended transition
state, which would have been disfavored by the methyl at C-1
of the diene, would be the favored geometry at C-4 of the
diene. Thus, it is reasonable that the reaction took place in low
yield but gave the products of the extended and the compact
transition states, i.e., 36 and 37, in essentially equal amounts.
Repositioning the α methyl group of the AVK, as in AVK 38,
led to a dramatic difference in the reactivity. In this instance,
the regioselectivity was reversed, and 40a,b was the (4 + 3)
product. This is consistent with a large steric interaction
between the methyl groups in transition state G (and in the
corresponding extended transition state), but with the opposite
regioselectivity there was no methyl−methyl interaction, and
the approximately 3:1 ratio of epimers reflected a small bias in
favor of a compact transition state.
1
films on a NaCl plate. Structures were determined using H and 13C
NMR spectra, including two- dimensional NMR experiments (COSY,
HSQC and HMBC). Relative stereochemistry was assigned using one-
dimensional NOE experiments.20
Procedure for Dienes 5, 8, and 9. On the basis of the work by
Jung and McCombs,9 a solution of α,β-unsaturated ketone (50 mmol)
in anhydrous DMF (3.5 mL) and a solution of Me3SiCl (62 mmol) in
DMF (3.5 mL) were both added dropwise over a period of 30 min to a
heated (84 °C) solution of Et3N (62 mmol) in DMF (30 mL).
Heating was continued overnight (14 h). The solution was then
allowed to attain rt before workup. The solution was diluted with
pentane (50 mL) and washed with cold 5% aqueous NaHCO3 (150
mL). The aqueous layer was re-extracted with pentane (2 × 50 mL),
and the combined organic extracts were washed with distilled water
(50 mL), dried over Na2SO4, and concentrated under vacuum. The
residue was distilled under reduced pressure.
CONCLUSIONS
■
The BF3·Et2O-mediated Nazarov reaction of the AVK 1
generates a cyclic oxyallyl cation intermediate that can be
intercepted by cycloaddition with an oxygen-substituted diene.
Unlike interception with hydrocarbon dienes which react by (3
+ 2) and (4 + 3) cycloadditions, the more electron-rich dienes
used in this study give the products of (4 + 3) cycloadditions
only, except when steric hindrance in the (4 + 3) process would
be very high. However, several factors conspire to reduce the
yields of the (4 + 3) products. The dienes themselves are
unstable under the reaction conditions, the (4 + 3) products
can undergo Lewis acid-mediated ring cleavage, and any
reaction of the diene in its s-trans conformation would lead to
an intermediate that cannot cyclize to the (4 + 3) product.
In spite of the generally modest yields, some important
features of these (4 + 3) cycloadditions have been revealed.
The regioselectivity is generally very high, with the more
electron-rich terminus of the diene reacting with the more
electrophilic carbon of the oxyallyl cation. The (4 + 3)
cycloaddition is a concerted reaction, with the compact
transition state having a somewhat lower energy barrier than
that of the extended transition state. This leads in some
instances to poor stereoselectivity. However, steric interactions
can influence this selectivity and examples of high selectivity are
now known. A computational study related to (4 + 3)
cycloaddition is now underway in our laboratories.
2-[(Trimethylsilyl)oxy]-1,3-butadiene (5). 3-Buten-2-one (4.1 mL,
50 mmol), Me3SiCl (7.9 mL, 62 mmol), and Et3N (8.6 mL, 62 mmol)
gave 5 (2.6 g, 37%) as a colorless liquid: bp 33−35 °C (22 mmHg);
1H NMR (500 MHz, CDCl3) δ 6.19 (dd, J = 16.9, 10.5 Hz, 1H), 5.47
(dd, J = 16.9, 1.5 Hz, 1H), 5.08 (br d, J = 10.5 Hz, 1H), 4.35 (s, 1H),
4.34 (s, 1H), 0.23 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 154.9,
134.6, 114.6, 96.5, 0.7 (3C). These data match those in the literature.9
(E)-2-[(Trimethylsilyl)oxy]-1,3-pentadiene (8). 3-Penten-2-one (4.9
mL, 50 mmol), Me3SiCl (7.9 mL, 62 mmol), and Et3N (8.6 mL, 62
mmol) gave 8 (3.3 g, 42%) as a colorless liquid: bp 36−37 °C (22
1
mmHg); H NMR (500 MHz, CDCl3) δ 5.96 (dq, J = 15.1, 6.4 Hz,
1H), 5.90 (d, J = 15.3 Hz, 1H), 4.20 (s, 2H), 1.76 (d, J = 6.4 Hz, 3H),
0.22 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 155.0, 129.1 126.7, 93.8,
17.7, 0.2 (3C). These data match those in the literature.21
(Z)-3-[(Trimethylsilyl)oxy]-1,3-pentadiene (9). 1-Penten-3-one (4.9
mL, 50 mmol), Me3SiCl (7.9 mL, 62 mmol), and Et3N (8.6 mL, 62
mmol) gave 9 (1.7 g, 21%) as a colorless liquid: bp 41−42 °C (22
1
mmHg); H NMR (500 MHz, CDCl3) δ 6.17 (dd, J = 17.1, 10.6 Hz,
1H), 5.24 (br d, J = 17.0 Hz, 1H), 4.93 (br d, J = 10.1 Hz, 1H), 4.87
(q, J = 7.0 Hz, 1H), 1.64 (d, J = 7.0 Hz, 3H), 0.21 (s, 9H); 13C NMR
(126 MHz, CDCl3) δ 149.9, 135.6, 111.5, 110.4, 11.7, 0.8 (3C). These
data match those in the literature.22
Procedure for Dienes 15−19. On the basis of the work of Jung
and Nishimura,11 a solution of α,β-unsaturated ketone (10 mmol) in
THF (40 mL) was cooled to 0 °C. Et3N (25 mmol) was added,
followed by the slow addition of tert-butyldimethylsilyl trifluorome-
thanesulfonate (TBSOTf) (11 mmol). The solution was stirred at 0
°C until the reaction was complete, as evidenced by TLC. The
solution was then diluted with pentane (80 mL) and washed with
saturated aqueous NaHCO3 (25 mL), water (2 × 25 mL), and brine
(25 mL). The organic layer was dried over MgSO4, filtered, and
concentrated under vacuum. The residue was purified by flash
chromatography (2% Et3N in pentane).
EXPERIMENTAL SECTION
■
General Considerations. Reactions were carried out using oven-
dried Teflon-coated magnetic stir bars in oven-dried glassware (150
°C), sealed with rubber septa under a positive nitrogen atmosphere.
Elevated temperatures were maintained using a silicone oil bath
controlled with a thermostat device. Temperatures of 0 and −78 °C
were achieved using ice/water and ethyl acetate/liquid nitrogen,
respectively. Concentration in vacuo was achieved using a rotary
evaporator (22 mmHg) with residual solvent being removed under
high vacuum (5 mmHg). Commercially available reagents were used
without further purification. Tetrahydrofuran (THF) was distilled over
sodium benzophenone under a dry nitrogen atmosphere. CH2Cl2 was
distilled over calcium hydride under a dry nitrogen atmosphere. Thin-
layer chromatography (TLC) was performed using 250 μm aluminum-
backed F254 silica gel plates. The plates were visualized by ultraviolet
light (254 nm) and treated with o-vanillin or potassium permanganate
stains followed by heating on a hot plate. Flash chromatography was
carried out on 230−400 mesh (40−63 μm) silica gel.
2-[(tert-Butyldimethylsilyl)oxy]-3-methyl-1,3-butadiene (15). 3-
Methyl-3-buten-2-one (1.0 mL, 10 mmol), TBSOTf (2.5 mL, 11
mmol), and Et3N (3.5 mL, 25 mmol) were stirred for 1 h at 0 °C to
1
give 15 (0.34 g, 17%) as a colorless liquid: H NMR (500 MHz,
CDCl3) δ 5.43 (narrow m, 1H), 4.96 (narrow m, 1H), 4.47 (narrow
m, 1H), 4.32 (narrow m, 1H), 1.87 (s, 3H), 0.97 (s, 9H), 0.17 (s, 6H);
13C NMR (126 MHz, CDCl3) δ 156.6, 140.0, 113.8, 92.9, 26.0 (3C),
19.8, 18.4, −4.6 (2C). These data match those in the literature.23
(E)-2-[(tert-Butyldimethylsilyl)oxy]-1,3-pentadiene (16). 3-Penten-
2-one (0.98 mL, 10 mmol), TBSOTf (2.5 mL, 11 mmol), and Et3N
(3.5 mL, 25 mmol) were stirred for 1 h at 0 °C to give 16 (1.50 g,
73%) as a colorless liquid: 1H NMR (500 MHz, CDCl3) δ 6.00 (dq, J
= 15.1, 6.7 Hz, 1H), 5.89 (dq, J = 15.1, 1.5 Hz, 1H), 4.19 (s, 1H), 4.18
(s, 1H), 1.77−1.75 (m, 3H), 0.97 (s, 9H), 0.17 (s, 6H); 13C NMR
E
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(126 MHz, CDCl3) δ 155.2, 129.3, 126.5, 93.6, 26.0 (3C), 18.4, 17.8,
−4.5 (2C). These data match those in the literature.11
7.5 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H), 6.31 (dd, J = 17.1, 10.7 Hz, 1H),
5.78 (s, 1H), 5.48 (d, J = 17.1 Hz, 1H), 5.13 (d, J = 10.7 Hz, 1H), 0.99
(s, 9H), −0.12 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 149.8, 136.5,
136.3, 129.3 (2C), 128.0 (2C), 126.4, 114.6, 114.5, 26.1 (3C), 18.5,
1-[(tert-Butyldimethylsilyl)oxy]-1-(1-cyclohexenyl)ethene (17). 1-
Acetyl-1-cyclohexene (1.3 mL, 10 mmol), TBSOTf (2.5 mL, 11
mmol), and Et3N (3.5 mL, 25 mmol) were stirred for 2 h at 0 °C to
1
−3.6 (2C). For the E-isomer: H NMR (500 MHz, CDCl3) δ 7.30−
1
give 17 (2.15 g, 90%) as a colorless liquid: H NMR (500 MHz,
7.17 (m, 5H), 6.68 (dd, J = 16.9, 10.7 Hz, 1H), 6.01 (s, 1H), 5.67 (d, J
= 16.9 Hz, 1H), 5.18 (d, J = 10.7 Hz, 1H), 1.01 (s, 9H), 0.23 (s, 6H);
13C NMR (126 MHz, CDCl3) δ 150.1, 136.6, 131.2, 129.4 (2C), 128.3
(2C), 126.3, 116.5, 113.8, 26.1 (3C), 18.6, −4.2 (2C). For the mixture
of isomers: IR (thin film) 1630, 1472, 1362, 1254, 1085, 839, 781
cm−1; HRMS (ESI) calcd for [C16H25OSi]+ 261.1669, found 261.1680.
(Z)-3-[(tert-Butyldimethylsilyl)oxy]-5-methyl-1,3-hexadiene (23).
5-Methylhex-1-en-3-one29 (1.12 g, 10 mmol), TBSOTf (2.5 mL, 11
mmol), and KN(SiMe3)2 (10 mL, 10 mmol) gave 23 (2.08 g, 92%) as
CDCl3) δ 6.26−6.24 (narrow m, 1H), 4.34 (s, 1H), 4.18 (s, 1H),
2.14−2.12 (narrow m, 4H), 1.68−1.57 (m, 4H), 0.97 (s, 9H), 0.17 (s,
6H); 13C NMR (126 MHz, CDCl3) δ 156.9, 133.3, 125.5, 89.6, 26.0
(3C), 25.6, 25.1, 22.9, 22.3, 18.5, −4.5 (2C). These data match those
in the literature.11
2-[(tert-Butyldimethylsilyl)oxy]-4-methyl-1,3-pentadiene (18). 4-
Methyl-3-penten-2-one (1.1 mL, 10 mmol), TBSOTf (2.5 mL, 11
mmol), and Et3N (3.5 mL, 25 mmol) were stirred for 1 h at 0 °C to
1
1
give 18 (1.95 g, 90%) as a colorless liquid: H NMR (500 MHz,
a colorless liquid: H NMR (500 MHz, CDCl3) δ 6.10 (dd, J = 17.1,
CDCl3) δ 5.56 (s, 1H), 4.30 (s, 1H), 4.16 (s, 1H), 1.89 (s, 3H), 1.77
(s, 3H), 0.94 (s, 9H), 0.16 (s, 6H); 13C NMR (126 MHz, CDCl3) δ
155.8, 136.8, 123.3, 95.0, 27.1, 26.0 (3C), 20.0, 18.5, −4.3 (2C). These
data match those in the literature.24
10.8 Hz, 1H), 5.26 (d, J = 17.1 Hz, 1H), 4.93 (d, J = 10.8 Hz, 1H),
4.60 (d, J = 9.7 Hz, 1H), 2.75−2.65 (m, 1H), 0.98 (s, 9H), 0.94 (d, J =
7.3 Hz, 6H), 0.11 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 146.6,
136.1, 123.5, 112.2, 26.2 (3C), 25.1, 23.1 (2C), 18.6, −3.6 (2C); IR
(thin film): 1253, 1053, 844 cm−1; HRMS (ESI) calcd for
[C13H26OSiNa]+ 249.1645, found 249.1653.
(Z)-3-[(tert-Butyldimethylsilyl)oxy]-1,3-pentadiene (19). 1-Penten-
3-one (1.0 mL, 10 mmol), TBSOTf (2.5 mL, 11 mmol), and Et3N (3.5
mL, 25 mmol) were stirred for 1 h at 0 °C to give 19 (1.16 g, 59%) as
(2Z,4E)-3-[(tert-Butyldimethylsilyl)oxy]-2,4-hexadiene (35). 4-
Hexen-3-one (1.1 mL, 10 mmol), TBSOTf (2.5 mL, 11 mmol), and
KN(SiMe3)2 (10 mL, 10 mmol) gave 35 (1.06 g, 50%) as a colorless
liquid: 1H NMR (500 MHz, CDCl3) δ 5.85 (br d, J = 15.4, 1H), 5.74
(dq, J = 15.4, 6.6 Hz, 1H), 4.72 (q, J = 7.0 Hz, 1H), 1.73 (d, J = 6.6
Hz, 3H), 1.61 (d, J = 7.0 Hz, 3H), 1.00 (s, 9H), 0.10 (s, 6H); 13C
NMR (126 MHz, CDCl3) δ 149.2, 130.0, 123.5, 107.1, 26.1 (3C),
18.6, 17.8, 11.8, −3.5 (2C); IR (thin film) 1255, 1073, 837 cm−1;
HRMS (ESI) calcd for [C12H25OSi]+ 213.1669, found 213.1667.
Procedure for Compounds 6, 7, 10−14, 24−34, and 36−40.
BF3·OEt2 (0.44 mmol) was added to a solution of the allenyl vinyl
ketone5a,7 (0.40 mmol) and the diene (2.0 mmol) in CH2Cl2 (40 mL)
at −78 °C. The solution was stirred for 5 min, and then saturated
aqueous NaHCO3 (40 mL) was added at −78 °C. After the solution
was warmed to rt, the aqueous layer was extracted with CH2Cl2 (3 ×
40 mL). The combined organic solutions were dried over Na2SO4 and
concentrated under vacuum. The residue was purified by flash
chromatography (5% Et2O in pentane).
1
a colorless liquid: H NMR (500 MHz, CDCl3) δ 6.16 (dd, J = 17.1,
10.8 Hz, 1H), 5.27 (d, J = 17.1 Hz, 1H), 4.94 (d, J = 10.8 Hz, 1H),
4.87 (q, J = 7.1 Hz, 1H), 1.64 (d, J = 7.1 Hz, 3H), 1.01 (s, 9H), 0.12
(s, 6H); 13C NMR (126 MHz, CDCl3) δ 149.5, 135.7, 111.8, 110.3,
25.9 (3C), 18.3, 12.0, −2.8, −3.5. These data match those in the
literature.25
Procedure for 3-Methoxy-4-methyl-1,3-pentadiene (20). A
solution of dimethyl 1-methoxyallylphosphonate (1.7 g, 9.6 mmol) in
THF (5 mL) was added to a solution of LDA (11.5 mmol) in THF
(20 mL) at −78 °C and the mixture stirred for 30 min. A solution of
acetone (0.74 mL, 9.6 mmol) in THF (5 mL) was added to the
mixture. The mixture was allowed to warm slowly to rt over 1 h. The
reaction was quenched by addition of saturated aqueous NH4Cl (25
mL), and the mixture was extracted with Et2O (25 mL). The organic
layer was washed with brine (25 mL), dried over MgSO4, filtered, and
concentrated under vacuum. The residue was purified by flash
chromatography (10% Et2O in pentane) to give 20 (0.30 g, 28%) as a
1
colorless liquid: H NMR (500 MHz, CDCl3) δ 6.46 (dd, J = 17.1,
(1R*,6S*,7S*)-1-Methyl-8-methylene-7-phenyl-4-[(trimethylsilyl)-
oxy]bicyclo[4.2.1]non-3-en-9-one (6) and (1R*,6S*,7S*)-1-Methyl-
8-methylene-7-phenylbicyclo[4.2.1]nonane-4,9-dione (7). AVK 1
(70 mg, 0.40 mmol), 5 (0.28 g, 2.0 mmol), and BF3·OEt2 (0.05 mL,
0.44 mmol) gave 6 (35 mg, 27%) and 7 (24 mg, 24%) as colorless oils.
For 6: 1H NMR (500 MHz, CDCl3) δ 7.28−7.26 (m, 2H), 7.19 (tt, J
= 7.4, 1.5 Hz, 1H), 7.04−7.02 (m, 2H), 5.09 (d, J = 2.4 Hz, 1H), 4.96
(dt, J = 7.4, 2.5 Hz, 1H), 4.86 (d, J = 2.1 Hz, 1H), 3.80 (q, J = 2.1 Hz,
1H), 2.70−2.68 (m, 1H), 2.57−2.52 (m, 1H), 2.38−2.30 (m, 2H),
2.15 (dd, J = 15.8, 7.4 Hz, 1H), 1.30 (s, 3H), 0.19 (s, 9H); 13C NMR
(126 MHz, CDCl3) δ 222.0, 157.7, 149.1, 146.3, 128.9 (2C), 127.5
(2C), 126.6, 110.0, 106.9, 54.7, 53.5, 52.0, 42.6, 37.3, 21.2, 0.5 (3C);
IR (thin film) 1750 cm−1; HRMS (ESI) calcd for [C20H26O2SiNa]+
349.1594, found 349.1581. For 7: 1H NMR (500 MHz, CDCl3) δ 7.29
(t, J = 7.5 Hz, 2H), 7.22 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 7.4 Hz, 2H),
5.25 (d, J = 1.9 Hz, 1H), 5.12 (d, J = 1.7 Hz, 1H), 3.87 (q, J = 1.8 Hz,
1H), 2.86−2.84 (m 1H), 2.78 (dd, J = 15.1, 5.8 Hz, 1H), 2.68−2.62
(m, 1H), 2.60−2.52 (m, 2H), 1.95−1.90 (m, 1H), 1.87−1.82 (m, 1H),
1.31 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 220.2, 209.4, 156.1,
145.0, 129.1 (2C), 127.1 (2C), 127.0, 113.0, 54.0, 53.0, 51.3, 45.5,
41.3, 40.0, 22.3; IR (thin film) 1743, 1704 cm−1; HRMS (ESI) calcd
for [C17H18O2Na]+ 277.1199, found 277.1196.
10.8 Hz, 1H), 5.33 (d, J = 17.0 Hz, 1H), 5.04 (dd, J = 10.8, 0.4 Hz,
1H), 3.52 (s, 3H), 1.77 (s, 3H), 1.74 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 149.1, 127.9, 122.0, 112.3, 59.0, 18.5, 18.0. These data
match those in the literature.26
Procedure for Dienes 21−23 and 35. On the basis of the work
by Carreno et al.,25 a solution of α,β-unsaturated ketone (10 mmol)
̃
and TBSOTf (11 mmol) in THF (80 mL) was cooled to −78 °C. A 1
M solution of potassium bis(trimethylsilyl)amide (KN(SiMe3)2) in
THF (10 mmol) was slowly added. The solution was stirred at −78 °C
for 30 min and then allowed to warm to rt with stirring for 1 h.
Saturated aqueous NaHCO3 (80 mL) was added, and the mixture was
extracted with Et2O (80 mL). The organic solution was washed with
brine (80 mL), dried over MgSO4, filtered, and concentrated under
vacuum. The residue was purified by flash chromatography (2% Et3N
in pentane).
(Z)-3-[(tert-Butyldimethylsilyl)oxy]-1,3-hexadiene (21). 1-Hexen-
3-one (1.2 mL, 10 mmol), TBSOTf (2.5 mL, 11 mmol), and
KN(SiMe3)2 (10 mL, 10 mmol) gave 21 (1.59 g, 75%) as a colorless
1
liquid: H NMR (500 MHz, CDCl3) δ 6.14 (dd, J = 17.2, 10.8 Hz,
1H), 5.28 (dd, J = 17.1, 1.0 Hz, 1H), 4.94 (dd, J = 10.8, 0.8 Hz, 1H),
4.76 (t, J = 7.2 Hz, 1H), 2.12 (quintet, J = 7.4 Hz, 2H), 1.00 (s, 9H),
0.96 (t, J = 7.5 Hz, 3H), 0.11 (s, 6H); 13C NMR (126 MHz, CDCl3) δ
148.0, 135.9, 118.0, 112.0, 26.2 (3C), 19.5, 18.6, 14.2, −3.5 (2C); IR
(thin film) 1255, 1050, 839, 780 cm−1; HRMS (APCI) calcd for
[C12H25OSi]+ 213.1669, found 213.1663.
2-[(tert-Butyldimethylsilyl)oxy]-1-phenyl-1,3-butadiene (22). 1-
Phenylbut-3-en-2-one27 (1.46 g, 10 mmol), TBSOTf (2.5 mL, 11
mmol), and KN(SiMe3)2 (10 mL, 10 mmol) gave a 1:1 mixture of E:Z
isomers of 2228 (1.30 g, 50%) as a colorless liquid. For the Z-isomer:
1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 7.8 Hz, 2H), 7.26 (t, J =
(1R*,2R*,6S*,7S*)-1,2-Dimethyl-8-methylene-7-phenyl-4-
[(trimethylsilyl)oxy]bicyclo[4.2.1]non-3-en-9-one (10),
(1R*,2R*,6S*,7S*)-1,2-Dimethyl-8-methylene-7-phenylbicyclo-
[4.2.1]nonane-4,9-dione (11), and (4R*,5R*)-2,3-Dimethyl-5-((E)-2-
oxopent-3-en-1-yl)-4-phenylcyclopent-2-enone (12). AVK 1 (70 mg,
0.40 mmol), 8 (0.31 g, 2.0 mmol), and BF3·OEt2 (0.05 mL, 0.44
mmol) gave 10 (11 mg, 8%), 11 (19 mg, 18%), and 12 (24 mg, 22%)
1
as colorless oils. For 10: H NMR (500 MHz, CDCl3) δ 7.30−7.27
(m, 2H), 7.23−7.20 (m, 1H), 7.08−7.06 (m, 2H), 5.00 (d, J = 2.9 Hz,
F
DOI: 10.1021/acs.joc.5b00914
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1H), 4.79−4.78 (m, 2H), 3.71 (q, J = 3.2 Hz, 1H), 2.65 (q, J = 4.2 Hz,
1H), 2.62−2.58 (m, 1H), 2.38−2.32 (m, 2H), 1.24 (s, 3H), 1.07 (d, J
= 7.1 Hz, 3H), 0.19 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 221.8,
154.2, 147.2, 145.6, 128.9 (2C), 128.2 (2C), 126.7, 115.5, 112.5, 58.4,
53.3, 52.2, 40.8, 37.8, 19.5, 17.7, 0.5 (3C); IR (thin film) 1747 cm−1;
HRMS (ESI) calcd for [C21H28O2SiNa]+ 363.1751, found 363.1754.
3H), 0.96 (s, 9H), 0.13 (s, 3H), 0.13 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 222.5, 157.2, 146.3, 142.3, 128.9 (2C), 127.4 (2C), 126.5,
113.9, 109.7, 54.1, 53.8, 51.5, 38.7, 26.1 (3C), 21.0, 20.9, 18.4, −3.4,
−3.6; IR (thin film): 1737 cm−1; HRMS (ESI) calcd for
[C24H34O2SiNa]+ 405.2220, found 405.2229.
(1R*,2R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,2-dimethyl-
8-methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (25) and
(4R*,5R*)-2,3-Dimethyl-5-((E)-2-oxopent-3-en-1-yl)-4-phenylcyclo-
pent-2-enone (12). AVK 1 (70 mg, 0.40 mmol), 16 (0.40 g, 2.0
mmol), and BF3·OEt2 (0.05 mL, 0.44 mmol) were stirred for 5 min at
−78 °C to give 25 (41 mg, 27%) as a colorless solid and 12 (37 mg,
1
For 11: H NMR (500 MHz, CDCl3) δ 7.32−7.28 (m, 2H), 7.25−
7.21 (m, 1H), 7.07−7.05 (m, 2H), 5.16 (d, J = 2.8 Hz, 1H), 5.05 (d, J
= 2.4 Hz, 1H), 3.87 (q, J = 2.7 Hz, 1H), 2.85−2.78 (m, 2H), 2.61−
2.51 (m, 3H), 1.26 (s, 3H), 1.04 (d, J = 6.8 Hz, 3H); 13C NMR (126
MHz CDCl3) δ 220.7, 208.5, 152.8, 146.0, 129.1 (2C), 127.7 (2C),
127.0, 115.4, 58.1, 54.0, 51.5, 50.4, 46.2, 40.7, 19.9, 16.2; IR (thin film)
1744, 1712 cm−1; HRMS (ESI) calcd for [C18H20O2Na]+ 291.1356,
1
35%) as a colorless oil. For 25: mp 93−94 °C; H NMR (500 MHz,
CDCl3) δ 7.30−7.28 (m, 2H), 7.23−7.20 (m, 1H), 7.09−7.07 (m,
2H), 4.99 (d, J = 2.9 Hz, 1H), 4.79 (d, J = 2.5 Hz, 1H), 4.78 (t, J = 2.5
Hz, 1H), 3.72 (q, J = 3.2 Hz, 1H), 2.66 (q, J = 4.2 Hz, 1H), 2.63−2.58
(m, 1H), 2.38−2.32 (m, 2H), 1.24 (s, 3H), 1.08 (d, J = 7.1 Hz, 3H),
0.92 (s, 9H), 0.15 (s, 3H), 0.12 (s, 3H); 13C NMR (126 MHz, CDCl3)
δ 221.6, 154.2, 147.4, 145.5, 128.8 (2C), 128.2 (2C), 126.6, 115.1,
112.4, 58.4, 53.1, 52.2, 40.9, 37.7, 25.8 (3C), 19.5, 18.1, 17.7, −4.1,
−4.3; IR (thin film) 1734 cm−1; HRMS (ESI) calcd for
[C24H34O2SiNa]+ 405.2220, found 405.2204.
1
found 291.1348. For 12: H NMR (500 MHz, CDCl3) δ 7.31 (t, J =
7.3 Hz, 2H), 7.24 (t, J = 7.4 Hz, 1H), 7.06 (d, J = 7.6 Hz, 2H), 6.82
(dq, J = 15.5, 6.9 Hz, 1H), 6.08 (d, J = 15.8 Hz, 1H), 3.56 (s, 1H), 3.04
(dd, J = 16.9, 3.7 Hz, 1H), 2.80 (dd, J = 16.9, 7.8 Hz, 1H), 2.58 (t, J =
3.9 Hz, 1H), 1.86 (d, J = 6.8 Hz, 3H), 1.82 (s, 3H), 1.80 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 209.3, 198.1, 169.8, 143.3, 141.6, 136.4,
131.6, 129.0 (2C), 127.9 (2C), 127.2, 56.0, 51.9, 40.3, 18.4, 15.6, 8.6;
IR (thin film): 1700, 1648 cm−1; HRMS (ESI) calcd for
[C18H20O2Na]+ 291.1356, found 291.1352.
(1R*,2R*,10S*,11S*)-8-[(tert-Butyldimethylsilyl)oxy]-1-methyl-
12-methylene-11-phenyltricyclo[8.2,72.1]tridec-7-en-13-one (26).
AVK 1 (70 mg, 0.40 mmol), 17 (0.48 g, 2.0 mmol), and BF3·OEt2
(1R*,5S*,6S*,7S*)-1,5-Dimethyl-8-methylene-7-phenyl-4-
[(trimethylsilyl)oxy]bicyclo[4.2.1]non-3-en-9-one (13a),
(1R*,5R*,6S*,7S*)-1,5-Dimethyl-8-methylene-7-phenyl-4-
[(trimethylsilyl)oxy]bicyclo[4.2.1]non-3-en-9-one (13b),
(1R*,5S*,6S*,7S*)-1,5-Dimethyl-8-methylene-7-phenylbicyclo-
[4.2.1]nonane-4,9-dione (14a), and (1R*,5R*,6S*,7S*)-1,5-Dimeth-
yl-8-methylene-7-phenylbicyclo[4.2.1]nonane-4,9-dione (14b).
AVK 1 (70 mg, 0.40 mmol), 9 (0.31 g, 2.0 mmol), and BF3·OEt2
(0.05 mL, 0.44 mmol) gave a 5:1 mixture of 13a and 13b (89 mg,
66%) and a 1:1.2 mixture of 14a and 14b (31 mg, 29%) as colorless
oils. For 13a: 1H NMR (500 MHz, CDCl3) δ 7.30 (t, J = 7.5 Hz, 2H),
7.22 (t, J = 7.3 Hz, 1H), 7.06 (d, J = 7.8 Hz, 2H), 5.13 (d, J = 2.0 Hz,
1H), 4.90 (d, J = 1.2 Hz, 1H), 4.85 (dd, J = 7.7, 1.9 Hz, 1H), 3.80 (s,
1H), 2.54−2.52 (m, 2H), 2.33 (d, J = 16.0 Hz, 1H), 2.13 (dd, J = 15.9,
7.7 Hz, 1H), 1.32 (s, 3H), 1.20 (d, J = 6.4 Hz, 3H), 0.26 (s, 9H); 13C
NMR (126 MHz, CDCl3) δ 219.7, 157.5, 154.2, 146.6, 128.9 (2C),
127.4 (2C), 126.5, 109.8, 104.4, 59.7, 54.2, 53.0, 42.9, 41.6, 21.2, 17.6,
0.7 (3C). For 13b: 1H NMR (500 MHz, CDCl3) δ 7.30 (t, J = 7.5 Hz,
2H), 7.22 (t, J = 7.3 Hz, 1H), 7.08 (d, J = 7.8 Hz, 2H), 5.09 (d, J = 2.4
Hz, 1H), 4.98−4.97 (m, 1H), 4.76 (d, J = 1.7 Hz, 1H), 3.93 (d, J = 2.5
Hz, 1H), 2.72−2.71 (m, 1H), 2.64 (t, J = 3.3 Hz, 1H), 2.31−2.28 (m,
1H), 2.20−2.15 (m, 1H), 1.34 (s, 3H), 1.23 (d, J = 7.2 Hz, 3H), 0.23
(s, 9H); 13C NMR (126 MHz, CDCl3) δ 221.4, 158.4, 151.6, 146.5,
128.9 (2C), 128.0 (2C), 126.4, 109.4, 106.2, 60.8, 54.9, 48.6, 42.0,
39.4, 20.1, 17.5, 0.4 (3C). For 13a and 13b: IR (thin film) 1741 cm−1;
HRMS (ESI) calcd for [C21H28O2SiNa]+ 363.1751, found 363.1747.
1
(0.05 mL, 0.44 mmol) gave 26 (69 mg, 41%) as a colorless oil: H
NMR (500 MHz, CDCl3) δ 7.26−7.25 (m, 2H), 7.19−7.17 (m, 1H),
7.05−7.02 (m, 2H), 5.07 (d, J = 2.2 Hz, 1H), 4.90 (d, J = 2.0 Hz, 1H),
3.80 (q, J = 1.7 Hz, 1H), 3.09−3.06 (m, 1H), 2.67−2.62 (m, 2H),
2.49−2.45 (m, 1H), 2.08−2.05 (m, 2H), 1.84 (br d, J = 12.6 Hz, 1H),
1.73 (br d, J = 12.6 Hz, 1H), 1.42−1.38 (m, 2H), 1.27 (s, 3H), 1.26−
1.22 (m, 1H), 1.07−0.99 (m, 1H), 0.95 (s, 9H), 0.15 (s, 3H), 0.15 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 220.9, 159.9, 146.5, 138.1, 128.9
(2C), 127.1 (2C), 126.5, 123.6, 109.5, 58.4, 55.4, 53.5, 52.3, 38.4, 32.6,
30.8, 28.8, 27.7, 26.1 (3C), 20.8, 18.5, −3.4, −3.5; IR (thin film) 1729
cm−1; HRMS (ESI) calcd for [C27H39O2Si]+ 423.2714, found
423.2699.
(1R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,2,2-trimethyl-8-
methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (28). AVK 1 (70
mg, 0.40 mmol), 18 (0.42 g, 2.0 mmol), and BF31·OEt2 (0.05 mL, 0.44
mmol) gave 28 (63 mg, 40%) as a colorless oil: H NMR (500 MHz,
CDCl3) δ 7.27 (t, J = 7.5 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.06 (d, J =
7.8 Hz, 2H), 5.04 (d, J = 2.7 Hz, 1H), 4.85−4.82 (m, 2H), 3.75 (q, J =
2.6 Hz, 1H), 2.62−2.57 (m, 2H), 2.35 (dd, J = 17.8, 6.2 Hz, 1H), 1.22
(s, 3H), 1.12 (s, 3H), 1.01 (s, 3H), 0.93 (s, 9H), 0.16 (s, 3H), 0.12 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 220.9, 157.0, 146.6, 146.3, 128.8
(2C), 128.1 (2C), 126.5, 121.8, 113.3, 60.0, 53.6, 51.8, 40.6, 37.5, 26.3,
26.0, 25.9 (3C), 18.2, 17.1, −3.9, −4.3; IR (thin film) 1740 cm−1;
HRMS (ESI) calcd for [C25H36O2SiNa]+ 419.2377, found 419.2369.
(1R*,5S*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,5-dimethyl-8-
methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (29a),
(1R*,5R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,5-dimethyl-8-
methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (29b),
(1R*,5S*,6S*,7S*)-1,5-Dimethyl-8-methylene-7-phenylbicyclo-
[4.2.1]nonane-4,9-dione (14a), and (1R*,5R*,6S*,7S*)-1,5-Dimeth-
yl-8-methylene-7-phenylbicyclo[4.2.1]nonane-4,9-dione (14b).
AVK 1 (70 mg, 0.40 mmol), 19 (0.40 g, 2.0 mmol), and BF3·OEt2
(0.05 mL, 0.44 mmol) gave a 7:1 mixture of 29a and 29b (86 mg,
56%) and a 1:1.2 mixture of 14a and 14b (46 mg, 43%) as colorless
1
For 14a: H NMR (500 MHz, CDCl3) δ 7.30−7.26 (m, 2H), 7.23−
7.18 (m, 1H), 7.07−7.04 (m, 2H), 5.22 (d, J = 2.2 Hz, 1H), 5.08 (d, J
= 2.0 Hz, 1H), 3.96 (q, J = 2.1 Hz, 1H), 2.69−2.50 (m, 4H), 1.98−
1.80 (m, 2H), 1.27 (s, 3H), 1.25 (d, J = 7.0 Hz, 3H); 13C NMR (126
MHz, CDCl3) δ 218.8, 211.6, 156.2, 145.4, 129.1 (2C), 127.1 (2C),
1
126.9, 112.5, 58.3, 54.4, 54.2, 50.4, 40.6, 38.8, 22.1, 16.5. For 14b: H
NMR (500 MHz, CDCl3) δ 7.30−7.26 (m, 2H), 7.23−7.18 (m, 1H),
7.07−7.04 (m, 2H), 5.21 (d, J = 2.2 Hz, 1H), 5.00 (d, J = 1.9 Hz, 1H),
3.81 (q, J = 2.1 Hz, 1H), 2.90 (qd, J = 6.8, 4.6 Hz, 1H), 2.69−2.50 (m,
3H), 1.98−1.80 (m, 2H), 1.31 (s, 3H), 1.21 (d, J = 6.8 Hz, 3H); 13C
NMR (126 MHz, CDCl3) δ 221.0, 211.2, 156.6, 145.1, 129.0 (2C),
127.3 (2C), 126.8, 112.7, 57.9, 53.2, 47.1, 46.9, 40.7, 40.5, 22.5, 13.9.
For 14a and 14b: IR (thin film) 1743, 1745, 1711, 1709 cm−1; HRMS
(ESI) calcd for [C18H20O2Na]+ 291.1356, found 291.1346.
(1R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,3-dimethyl-8-
methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (24). AVK 1 (70
mg, 0.40 mmol), 15 (0.40 g, 2.0 mmol), and BF31·OEt2 (0.05 mL, 0.44
mmol) gave 24 (54 mg, 35%) as a colorless oil: H NMR (500 MHz,
CDCl3) δ 7.26−7.25 (m, 2H), 7.20−7.17 (m, 1H), 7.03−7.01 (m,
2H), 5.08 (d, J = 2.4 Hz, 1H), 4.85 (d, J = 2.1 Hz, 1H), 3.80 (q, J = 2.0
Hz, 1H), 2.66−2.59 (m, 2H), 2.46 (dd, J = 16.4, 5.7 Hz, 1H), 2.40 (br
d, J = 15.6 Hz, 1H), 2.04 (d, J = 15.6 Hz, 1H), 1.64 (br s, 3H), 1.28 (s,
1
oils. For 29a: H NMR (500 MHz, CDCl3) δ 7.28−7.25 (m, 2H),
7.21−7.17 (m, 1H), 7.03−7.02 (m, 2H), 5.09 (d, J = 2.5 Hz, 1H), 4.85
(d, J = 2.1 Hz, 1H), 4.79 (dd, J = 7.6, 2.4 Hz, 1H), 3.75 (t, J = 2.1 Hz,
1H), 2.51−2.47 (m, 2H), 2.31−2.27 (m, 1H), 2.09 (dd, J = 16.0, 7.7
Hz, 1H), 1.28 (s, 3H), 1.17 (d, J = 6.8 Hz, 3H), 0.94 (s, 9H), 0.20 (s,
3H), 0.15 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 219.9, 157.5,
154.2, 146.5, 128.9 (2C), 127.4 (2C), 126.5, 109.8, 104.2, 59.7, 54.2,
1
53.0, 42.9, 41.7, 25.8 (3C), 21.2, 18.1, 17.6, −4.1, −4.2. For 29b: H
NMR (500 MHz, CDCl3) δ 7.27−7.24 (m, 2H), 7.19−7.16 (m, 1H),
7.04−7.02 (m, 2H), 5.07 (d, J = 2.3 Hz, 1H), 5.05 (dd, J = 7.2, 2.4 Hz,
1H), 4.88 (d, J = 2.0 Hz, 1H), 3.77 (d, J = 1.8 Hz, 1H), 2.64 (dd, J =
7.8, 3.2 Hz, 1H), 2.56−2.52 (m, 1H), 2.36−2.32 (m, 1H), 2.28−2.24
(m, 1H), 1.29 (s, 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.93 (s, 9H), 0.15 (s,
G
DOI: 10.1021/acs.joc.5b00914
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
3H), 0.11 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 220.3, 162.2,
159.7, 147.6, 128.9 (2C), 127.2 (2C), 126.5, 114.4, 109.7, 56.8, 53.7,
51.9, 46.4, 36.7, 25.9 (3C), 20.2, 18.2, 17.1, −4.0, −4.4. For 29a and
29b: IR (thin film) 1737 cm−1; HRMS (ESI) calcd for
[C24H34O2SiNa]+ 405.2220, found 405.2203.
For 32b: 1H NMR (500 MHz, CDCl3) δ 7.29−7.02 (m, 8H), 6.52 (d,
J = 6.5 Hz, 2H), 5.15 (d, J = 2.4 Hz, 1H), 5.08−5.07 (m, 1H), 4.82 (d,
J = 2.0 Hz, 1H), 4.10 (d, J = 2.4 Hz, 1H), 3.92−3.91 (m, 1H), 2.78
(dd, J = 5.0, 3.1 Hz, 1H), 2.43 (dt, J = 16.5, 3.3 Hz, 1H), 2.33 (dd, J =
17.9, 5.3 Hz, 1H), 1.35 (s, 3H), 0.58 (s, 9H), 0.05 (s, 3H), −0.10 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 219.8, 157.5, 148.4, 145.8,
140.0, 129.8 (2C), 128.4 (2C), 128.1 (2C), 127.0, 126.6, 126.0 (2C),
109.8, 108.6, 61.6, 54.6, 50.7, 47.5, 42.8, 25.4 (3C), 21.0, 17.8, −4.1,
(1R*,2S*,4S*,5S*)-2-(1-Methoxy-2-methylprop-1-en-1-yl)-1-
methyl-6-methylene-5-phenylbicyclo[2.2.1]heptan-7-one (30a) and
(1R*,2R*,4S*,5S*)-2-(1-Methoxy-2-methylprop-1-en-1-yl)-1-meth-
yl-6-methylene-5-phenylbicyclo[2.2.1]heptan-7-one (30b). AVK 1
(70 mg, 0.40 mmol), 20 (0.52 g, 2.0 mmol), and BF3·OEt2 (0.05 mL,
0.44 mmol) gave a 9:1 mixture of 30a and 30b (64 mg, 54%) as a
colorless oil. For 30a: 1H NMR (500 MHz, CDCl3) δ 7.25 (t, J = 7.5
Hz, 2H), 7.18 (t, J = 7.1 Hz, 1H), 7.11 (d, J = 7.8 Hz, 2H), 5.10 (d, J =
2.0 Hz, 1H), 4.81 (s, 1H), 3.78 (s, 1H), 3.55 (s, 3H), 3.04 (dd, J =
10.3, 5.1 Hz, 1H), 2.30 (d, J = 4.7 Hz, 1H), 2.24 (dt, J = 12.4, 5.0 Hz,
1H), 1.96 (dd, J = 12.2, 10.7 Hz, 1H), 1.71 (s, 3H), 1.64 (s, 3H), 1.08
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 214.0, 153.3, 150.7, 143.3,
128.6 (2C), 127.5 (2C), 126.7, 117.0, 107.9, 61.3, 52.9, 51.9, 48.1,
1
−5.1. For 33: H NMR (500 MHz, CDCl3) δ 7.29−7.02 (m, 10H),
5.02−5.01 (m, 1H), 4.54 (d, J = 2.5 Hz, 1H), 4.15 (d, J = 3.0 Hz, 1H),
3.92−3.91 (m, 1H), 3.35 (d, J = 1.8 Hz, 1H), 2.84 (q, J = 4.3 Hz, 1H),
2.71−2.66 (m, 1H), 2.52−2.48 (m, 1H), 1.19 (s, 3H), 0.51 (s, 9H),
−0.02 (s, 3H), −0.03 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 220.3,
153.3, 150.1, 145.1, 137.9, 128.8 (2C), 128.6 (2C), 127.5 (2C), 127.0,
126.7, 126.5 (2C), 114.6, 106.3, 57.7, 56.6, 55.8, 52.4, 32.2, 25.3 (3C),
21.4, 17.8, −4.4, −4.8. For 32b and 33: IR (thin film) 1745 cm−1;
HRMS (ESI) calcd for [C29H37O2Si]+ 445.2557, found 445.2556.
(1R*,5R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1-methyl-8-
methylene-7-phenyl-5-isopropylbicyclo[4.2.1]non-3-en-9-one (34).
AVK 1 (70 mg, 0.40 mmol), 23 (0.45 g, 2.0 mmol), and BF3·OEt2
(0.05 mL, 0.44 mmol) gave 34 (62 mg, 38%) as a colorless solid: mp
168−169 °C; 1H NMR (500 MHz, CDCl3) δ 7.25 (t, J = 7.5 Hz, 2H),
7.17 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 7.3 Hz, 2H), 4.99−4.96 (m, 2H),
4.61 (d, J = 2.2 Hz, 1H), 3.74 (q, J = 2.4 Hz, 1H), 2.74 (br s, 1H),
2.46−2.41 (m, 1H), 2.39 (br s, 1H), 2.15−2.05 (m, 2H), 1.26 (s, 3H),
0.95 (s, 9H), 0.89 (d, J = 6.8 Hz, 3H), 0.84 (d, J = 6.8 Hz, 3H), 0.21
(s, 3H), 0.15 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 223.0, 159.1,
153.4, 146.2, 128.7 (2C), 128.2 (2C), 126.3, 109.0, 104.4, 56.1, 54.4,
51.3, 49.7, 41.2, 28.5, 26.1 (3C), 21.9, 19.9, 19.6, 18.4, −4.1, −4.4; IR
(thin film) 1737 cm−1; HRMS (ESI) calcd for [C26H38O2SiNa]+
433.2533, found 433.2533.
1
43.4, 28.7, 19.7, 18.7, 9.4. For 30b: H NMR (500 MHz, CDCl3) δ
7.26 (t, J = 7.4 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.11 (d, J = 7.8 Hz,
2H), 4.95 (d, J = 2.6 Hz, 1H), 4.77 (d, J = 2.1 Hz, 1H), 3.83 (s, 1H),
3.59 (s, 3H), 3.13 (dd, J = 10.8, 6.5 Hz, 1H), 2.17−2.08 (m, 2H), 1.95
(d, J = 10.4 Hz, 1H), 1.76 (s, 3H), 1.66 (s, 3H), 1.12 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 215.1, 150.4, 149.8, 143.9, 128.7 (2C),
127.7 (2C), 126.7, 119.1, 109.6, 61.9, 55.1, 52.9, 48.2, 41.3, 28.1, 20.1,
19.3, 11.4. For 30a and 30b: IR (thin film) 1777, 1767 cm−1; HRMS
(ESI) calcd for [C20H24O2Na]+ 319.1669, found 319.1670.
(1R*,5S*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-5-ethyl-1-
methyl-8-methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (31a)
and (1R*,5R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-5-ethyl-1-
methyl-8-methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (31b).
AVK 1 (70 mg, 0.40 mmol), 21 (0.42 g, 2.0 mmol), and BF3·OEt2
(0.05 mL, 0.44 mmol) gave a 2:1 mixture of 31a and 31b (54 mg,
34%) as a colorless oil. For 31a: 1H NMR (500 MHz, CDCl3) δ 7.27
(t, J = 7.4 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.03 (d, J = 7.3 Hz, 2H),
5.09 (d, J = 2.3 Hz, 1H), 4.86 (d, J = 2.0 Hz, 1H), 4.81 (dd, J = 8.2, 2.3
Hz, 1H), 3.72 (d, J = 1.9 Hz, 1H), 2.69 (dd, J = 5.3, 1.8 Hz, 1H),
2.29−2.25 (m, 2H), 2.06 (dd, J = 15.9, 8.2 Hz, 1H), 1.64−1.62 (m,
1H), 1.48−1.35 (m, 1H), 1.27 (s, 3H), 0.99 (t, J = 7.4 Hz, 3H), 0.95
(s, 9H), 0.22 (s, 3H), 0.17 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
220.0, 157.5, 154.3, 146.7, 128.9 (2C), 127.4 (2C), 126.5, 109.8, 104.1,
56.2, 54.4, 52.8, 50.3, 41.3, 25.8 (3C), 24.5, 21.0, 18.1, 12.6, −4.1,
(1R*,2R*,5R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,2,5-tri-
methyl-8-methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (36)
and (1R*,2S*,5S*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1,2,5-tri-
methyl-8-methylene-7-phenylbicyclo[4.2.1]non-3-en-9-one (37).
AVK 1 (70 mg, 0.40 mmol), 35 (0.42 g, 2.0 mmol), and BF3·OEt2
(0.05 mL, 0.44 mmol) gave a mixture of 36 (32 mg, 20%) and 37 (35
1
mg, 22%) as colorless oils. For 36: H NMR (500 MHz, CDCl3) δ
7.28 (t, J = 7.5 Hz, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.10 (d, J = 7.8 Hz,
2H), 4.93 (d, J = 2.7 Hz, 1H), 4.73 (s, 1H), 4.63 (d, J = 1.8 Hz, 1H),
3.78 (t, J = 2.2 Hz, 1H), 2.76−2.74 (m, 1H), 2.64 (t, J = 4.6 Hz, 1H),
2.30−2.26 (m, 1H), 1.23 (s, 3H), 1.12 (d, J = 7.1 Hz, 3H), 1.04 (d, J =
6.8 Hz, 3H), 0.93 (s, 9H), 0.14 (s, 3H), 0.11 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 220.4, 154.8, 150.0, 145.5, 128.8 (2C), 128.7 (2C),
126.5, 113.9, 111.6, 59.7, 58.4, 49.0, 40.6, 40.2, 26.0 (3C), 18.7, 18.3,
18.0, 17.1, −4.1, −4.4. For 37: 1H NMR (500 MHz, CDCl3) δ 7.26 (t,
J = 7.5 Hz, 2H), 7.18 (t, J = 7.3 Hz, 1H), 7.02 (d, J = 7.7 Hz, 2H), 5.06
(d, J = 1.5 Hz, 1H), 4.89 (d, J = 7.2 Hz, 1H), 4.86 (s, 1H), 3.73 (s,
1H), 2.46−2.44 (m, 2H), 2.22 (quintet, J = 7.0 Hz, 1H), 1.29 (s, 3H),
1.16 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.95 (s, 9H), 0.21
(s, 3H), 0.16 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 218.5, 159.6,
152.5, 146.9, 128.9 (2C), 127.2 (2C), 126.4, 112.1, 109.5, 59.9, 56.5,
53.0, 46.1, 42.9, 25.9 (3C), 20.3, 18.4, 18.2, 17.8, −3.9, −4.2. For 36
and 37: IR (thin film) 1740 cm−1; HRMS (ESI) calcd for
[C25H36O2SiNa]+ 419.2377, found 419.2362.
(1R*,6S*,8R*)-4-[(tert-Butyldimethylsilyl)oxy]-1,5,5-trimethyl-7-
methylene-8-phenylbicyclo[4.2.1]non-3-en-9-one (39). AVK 38 (70
mg, 0.40 mmol), 18 (0.40 g, 2.0 mmol), and BF31·OEt2 (0.05 mL, 0.44
mmol) gave 39 (43 mg, 27%) as a colorless oil: H NMR (500 MHz,
CDCl3) δ 7.25 (t, J = 7.4 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H), 7.03 (d, J =
7.3 Hz, 2H), 5.15 (d, J = 2.5 Hz, 1H), 4.90 (s, 1H), 4.83 (d, J = 1.9 Hz,
1H), 3.95 (d, J = 1.7 Hz, 1H), 2.81 (s, 1H), 2.31 (dd, J = 16.8, 2.3 Hz,
1H), 2.17 (d, J = 16.8 Hz, 1H), 1.25 (s, 3H), 1.17 (s, 3H), 0.94 (s,
9H), 0.63 (s, 3H), 0.17 (s, 3H), 0.12 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 219.3, 149.5, 146.7, 143.1, 130.1, 128.2 (2C), 126.7 (2C),
118.8, 114.4, 65.9, 57.2, 51.1, 47.7, 38.9, 30.6, 29.2, 25.9 (3C), 21.0,
18.2, −4.0, −4.3; IR (thin film): 1742 cm−1; HRMS (ESI) calcd for
[C25H36O2SiNa]+ 419.2377, found 419.2371.
1
−4.3. For 31b: H NMR (500 MHz, CDCl3) δ 7.27 (t, J = 7.4 Hz,
2H), 7.19 (t, J = 7.3 Hz, 1H), 7.07 (d, J = 7.3 Hz, 2H), 5.03 (d, J = 2.7
Hz, 1H), 4.92−4.89 (m, 1H), 4.63 (d, J = 2.3 Hz, 1H), 3.90 (q, J = 3.0
Hz, 1H), 2.81 (t, J = 3.9 Hz, 1H), 2.42−2.39 (m, 1H), 2.29−2.25 (m,
1H), 2.19−2.14 (m, 2H), 1.48−1.35 (m, 1H), 1.30 (s, 3H), 0.94 (s,
9H), 0.67 (t, J = 7.4 Hz, 3H), 0.15 (s, 3H), 0.12 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 221.4, 158.8, 151.5, 145.9, 128.8 (2C), 128.1
(2C), 126.4, 108.9, 105.9, 55.9, 55.5, 48.4, 46.8, 41.8, 26.0 (3C), 22.3,
19.9, 18.4, 11.9, −4.1, −4.4. For 31a and 31b: IR (thin film) 1743
cm−1; HRMS (ESI) calcd for [C25H36O2SiNa]+ 419.2377, found
419.2382.
(1R*,5S*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1-methyl-8-
methylene-5,7-diphenylbicyclo[4.2.1]non-3-en-9-one (32a),
(1R*,5R*,6S*,7S*)-4-[(tert-Butyldimethylsilyl)oxy]-1-methyl-8-meth-
ylene-5,7-diphenylbicyclo[4.2.1]non-3-en-9-one (32b), and
(1R*,2R*,6S*,7S*)-3-[(tert-Butyldimethylsilyl)oxy]-1-methyl-8-meth-
ylene-2,7-diphenylbicyclo[4.2.1]non-3-en-9-one (33). AVK 1 (70
mg, 0.40 mmol), 22 (0.52 g, 2.0 mmol), and BF3·OEt2 (0.05 mL, 0.44
mmol) gave 32a (59 mg, 33%) and a 1.3:1 mixture of 32b and 33 (37
1
mg, 21%) as colorless oils. For 32a: H NMR (500 MHz, CDCl3) δ
7.28−7.17 (m, 6H), 7.05 (d, J = 7.3 Hz, 4H), 5.14 (d, J = 2.3 Hz, 1H),
5.07 (dd, J = 7.9, 2.3 Hz, 1H), 4.92 (d, J = 2.0 Hz, 1H), 3.97 (d, J = 2.0
Hz, 1H), 3.74 (d, J = 4.7 Hz, 1H), 2.75 (dd, J = 4.8, 2.0 Hz, 1H), 2.51
(d, J = 16.1 Hz, 1H), 2.23 (dd, J = 16.1, 7.9 Hz, 1H), 1.28 (s, 3H), 0.75
(s, 9H), 0.13 (s, 3H), −0.11 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
217.8, 157.2, 151.7, 146.4, 139.3, 128.9 (2C), 128.45 (2C), 128.37
(2C), 127.39 (2C), 127.21, 126.6, 110.2, 106.5, 60.7, 54.8, 54.3, 53.2,
41.7, 25.6 (3C), 21.4, 18.0, −4.1, −4.7; IR (thin film) 1744 cm−1;
HRMS (ESI) calcd for [C29H36O2SiNa]+ 467.2377, found 467.2381.
(1R*,5R*,6S*,8R*)-4-[(tert-Butyldimethylsilyl)oxy]-1,5-dimethyl-
7-methylene-8-phenylbicyclo[4.2.1]non-3-en-9-one (40a) and
H
DOI: 10.1021/acs.joc.5b00914
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(1R*,5S*,6S*,8R*)-4-[(tert-butyldimethylsilyl)oxy]-1,5-dimethyl-7-
methylene-8-phenylbicyclo[4.2.1]non-3-en-9-one (40b). AVK 38
(70 mg, 0.40 mmol), 19 (0.40 g, 2.0 mmol), and BF3·OEt2 (0.05
mL, 0.44 mmol) gave a 2.7:1 mixture of 40a and 40b (34 mg, 22%) as
a colorless oil. For 40a: 1H NMR (500 MHz, CDCl3) δ 7.26−7.22 (m,
2H), 7.18−7.15 (m, 1H), 6.96−6.93 (m, 2H), 5.16 (s, 1H), 4.93 (s,
1H), 4.80 (dd, J = 5.7, 4.6 Hz, 1H), 3.78 (s, 1H), 3.05 (dd, J = 5.7, 1.0
Hz, 1H), 2.47 (quintet, J = 6.7 Hz, 1H), 2.24−2.19 (m, 2H), 1.24 (d, J
= 7.1 Hz, 3H), 0.92 (s, 9H), 0.66 (s, 3H), 0.14 (s, 6H); 13C NMR
(126 MHz, CDCl3) δ 219.8, 155.3, 152.2, 144.5, 128.9, 128.4 (2C),
126.5 (2C), 111.6, 102.9, 57.9, 56.8, 54.4, 44.9, 41.5, 26.0 (3C), 20.4,
7.9 Hz, 2H), 7.22 (t, J = 7.2 Hz, 1H), 7.08 (d, J = 7.5 Hz, 2H), 3.96 (s,
1H), 2.87−2.83 (m, 1H), 2.68−2.59 (m, 4H), 2.42 (dd, J = 11.8, 4.4
Hz, 1H), 2.06−2.02 (m, 1H), 1.79 (s, 3H), 1.31 (d, J = 7.0 Hz, 3H),
1.23 (d, J = 6.4 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 213.1, 210.2,
175.8, 141.0, 135.7, 129.1 (2C), 127.4, 127.2 (2C), 64.6, 54.1, 53.5,
45.7, 35.9, 35.0, 23.7, 17.5, 9.4; IR (thin film) 1705, 1640 cm−1;
HRMS (ESI) calcd for [C19H22O2Na]+ 305.1512, found 305.1498.
(1R*,2S*,5S*,6S*,7S*)-1,2,5-Trimethyl-8-methylene-7-
phenylbicyclo[4.2.1]nonane-4,9-dione (45), (4R*,5R*)-2,3-Dimeth-
yl-5-((R*,E)-3-oxohex-4-en-2-yl)-4-phenylcyclopent-2-enone (46),
and (1R*,2R*,5S*,10R*)-2,5,8-Trimethyl-10-phenylbicyclo[5.2.1]-
dec-7-ene-3,9-dione (47). Compound 37 (35 mg, 0.40 mmol) and
BF3·OEt2 (0.05 mL, 0.44 mmol) gave 45 (4 mg, 15%), 46 (11 mg,
1
18.1, 16.7, −4.11, −4.15. For 40b: H NMR (500 MHz, CDCl3) δ
7.26−7.22 (m, 2H), 7.18−7.15 (m, 1H), 6.96−6.93 (m, 2H), 5.18 (s,
1H), 4.91−4.90 (m, 2H), 3.72 (s, 1H), 3.08 (s, 1H), 2.71−2.69 (m,
1H), 2.24−2.19 (m, 1H), 2.15−2.11 (m, 1H), 1.33 (d, J = 7.3 Hz,
3H), 0.93 (s, 9H), 0.67 (s, 3H), 0.16 (s, 3H), 0.15 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 222.2, 154.2, 149.6, 144.3, 129.4, 129.0 (2C),
128.3 (2C), 113.6, 102.7, 59.2, 58.1, 54.6, 41.4, 40.4, 25.8 (3C), 19.9,
18.4, 17.9, −4.23 (2C). For 40a and 40b: IR (thin film) 1742 cm−1;
HRMS (ESI) calcd for [C24H34O2SiNa]+ 405.2220, found 405.2217.
Procedure for Compounds 41−47. BF3·OEt2 (1.1 equiv) was
added to a solution of a Nazarov product in CH2Cl2 (0.1 M) at rt. The
solution was stirred for 5 min before saturated aqueous NaHCO3 (40
mL) was added. The aqueous layer was extracted with CH2Cl2 (3 × 40
mL). The combined organic solutions were dried over Na2SO4 and
concentrated under vacuum. The residue was purified by flash
chromatography (15% Et2O in pentane).
1
46%), and 47 (9 mg, 38%) as colorless oils. For 45: H NMR (500
MHz, CDCl3) δ 7.31 (t, J = 7.6 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 7.09
(d, J = 7.7 Hz, 2H), 5.24 (s, 1H), 5.10 (s, 1H), 4.00 (s, 1H), 3.00−2.97
(m, 1H), 2.63−2.62 (m, 2H), 2.43−2.39 (m, 1H), 2.00−1.97 (m, 1H),
1.28 (s, 3H), 1.26 (s, 3H), 0.96 (d, J = 7.0 Hz, 3H); 13C NMR
discernible signals (126 MHz, CDCl3) δ 146.0, 129.1 (2C), 127.1
(2C), 126.9, 112.2, 58.7, 57.3, 54.8, 50.4, 44.3, 20.4, 16.5; IR (thin
film): 1737, 1704 cm−1; HRMS (ESI) calcd for [C19H22O2Na]+
1
305.1512, found 305.1506. For 46: H NMR (500 MHz, CDCl3) δ
7.26−7.24 (m, 2H), 7.20−7.17 (m, 1H), 6.99 (d, J = 7.8 Hz, 2H), 6.73
(dq, J = 14.9, 7.3 Hz, 1H), 6.01 (d, J = 15.6 Hz, 1H), 3.57 (s, 1H),
3.38−3.33 (m, 1H), 2.67 (s, 1H), 1.80 (s, 3H), 1.79 (s, 3H), 1.70 (d, J
= 6.9 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ 208.9, 201.4, 171.5, 142.9, 141.4, 137.2, 130.0, 128.8 (2C), 128.0
(2C), 127.0, 56.6, 51.5, 44.0, 18.2, 15.6, 10.8, 8.4; IR (thin film) 1702,
1649 cm−1; HRMS (ESI) calcd for [C19H22O2Na]+ 305.1512, found
305.1513. For 47: 1H NMR (500 MHz, CDCl3) δ 7.30 (t, J = 7.5 Hz,
2H), 7.24 (t, J = 6.9 Hz, 1H), 7.14 (d, J = 7.7 Hz, 2H), 4.31 (s, 1H),
3.27 (dd, J = 6.6, 3.9 Hz, 1H), 3.01 (dd, J = 14.0, 3.3 Hz, 1H), 2.85 (d,
J = 3.7 Hz, 1H), 2.74 (dt, J = 7.0, 3.6 Hz, 1H), 2.64−2.60 (m, 1H),
2.52 (dd, J = 12.5, 3.8 Hz, 1H), 2.17 (dd, J = 14.0, 7.1 Hz, 1H), 1.68
(s, 3H), 1.28 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H); 13C NMR
(126 MHz, CDCl3) δ 211.1, 208.4, 173.5, 141.0, 135.2, 129.1 (2C),
127.5, 127.2 (2C), 65.4, 58.5, 53.3, 48.2, 35.3, 34.2, 22.7, 14.6, 9.4; IR
(thin film) 1703, 1641 cm−1; HRMS (ESI) calcd for [C19H22O2Na]+
305.1512, found 305.1499.
(4R*,5R*)-2,3-Dimethyl-5-((E)-2-oxopent-3-en-1-yl)-4-phenylcy-
clopent-2-enone (12). Compound 25 (41 mg, 0.11 mmol) and BF3·
OEt2 (0.01 mL, 0.12 mmol) gave 12 (29 mg, 90%) as a colorless oil.
(1R*,5S*,6S*,7S*)-1,5-Dimethyl-8-methylene-7-phenylbicyclo-
[4.2.1]nonane-4,9-dione (14a) and (1R*,5R*,6S*,7S*)-1,5-Dimeth-
yl-8-methylene-7-phenylbicyclo[4.2.1]nonane-4,9-dione (14b). A
7:1 mixture of 29a and 29b (86 mg, 0.22 mmol) and BF3·OEt2
(0.03 mL, 0.25 mmol) gave a 7:1 mixture of 14a and 14b (57 mg,
95%) as a colorless oil.
(1R*,5R*,6S*,7S*)-1-Methyl-8-methylene-7-phenyl-5-
isopropylbicyclo[4.2.1]nonane-4,9-dione (41). Compound 34 (62
mg, 0.40 mmol) and BF3·OEt2 (0.05 mL, 0.44 mmol) gave 41 (42 mg,
94%) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.29−7.26 (m,
2H), 7.20 (t, J = 7.4 Hz, 1H), 7.03 (d, J = 7.2 Hz, 2H), 5.16 (d, J = 2.1
Hz, 1H), 4.95 (d, J = 1.8 Hz, 1H), 3.88 (d, J = 2.0 Hz, 1H), 2.88 (dd, J
= 5.1, 2.4 Hz, 1H), 2.57−2.53 (m, 1H), 2.47−2.41 (m, 2H), 2.25−2.22
(m, 1H), 1.94−1.87 (m, 2H), 1.30 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H),
0.77 (d, J = 6.7 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 221.7, 210.8,
157.6, 146.0, 129.1 (2C), 127.3 (2C), 126.8, 112.4, 59.8, 54.4, 53.8,
47.2, 41.3, 40.5, 26.1, 22.3, 21.9, 20.4; IR (thin film) 1742, 1708 cm−1;
HRMS (ESI) calcd for [C20H24O2Na]+ 319.1669, found 319.1667.
(1R*,2R*,5R*,6S*,7S*)-1,2,5-Trimethyl-8-methylene-7-
phenylbicyclo[4.2.1]nonane-4,9-dione (42), (4R*,5R*)-2,3-Dimeth-
yl-5-((S*,E)-3-oxohex-4-en-2-yl)-4-phenylcyclopent-2-enone (43),
and (1R*,2S*,5S*,10R*)-2,5,8-Trimethyl-10-phenylbicyclo[5.2.1]-
dec-7-ene-3,9-dione (44). Compound 36 (32 mg, 0.40 mmol) and
BF3·OEt2 (0.05 mL, 0.44 mmol) gave 42 (1 mg, 5%), 43 (16 mg,
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra, NOE data, and the ORTEPs and the
CIFs for the X-ray analyses of 25 and 34. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.5b00914.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jean.burnell@dal.ca.
■
Notes
The authors declare no competing financial interest.
1
70%), and 44 (3 mg, 15%) as colorless oils. For 42: H NMR (500
MHz, CDCl3) δ 7.28 (t, J = 7.1 Hz, 2H), 7.20 (t, J = 7.4 Hz, 1H), 7.04
(d, J = 7.5 Hz, 2H), 5.10 (s, 1H), 4.93 (s, 1H), 3.71−3.70 (m, 1H),
2.95−2.93 (m, 1H), 2.65−2.59 (m, 2H), 2.39−2.36 (m, 1H), 2.04−
2.00 (m, 1H), 1.29 (s, 3H), 1.17 (d, J = 6.9 Hz, 3H), 1.02 (d, J = 6.9
Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 220.7, 210.7, 153.1, 146.3,
129.0 (2C), 128.0 (2C), 126.8, 115.2, 57.9, 57.6, 48.5, 48.1, 47.8, 40.3,
20.7, 16.6, 14.4; IR (thin film): 1740, 1708 cm−1; HRMS (ESI) calcd
ACKNOWLEDGMENTS
■
We thank Prof. T. Stanley Cameron for the X-ray crystal
structures, and we thank Dr. Zhe Li for the data regarding the
isomerization of the allyl cation. We are grateful to the Natural
Sciences and Engineering Research Council of Canada for
financial support of this research.
1
for [C19H22O2Na]+: 305.1512, found: 305.1500. For 43: H NMR
(500 MHz, CDCl3) δ 7.30 (t, J = 7.3 Hz, 2H), 7.23 (t, J = 7.0 Hz, 1H),
7.09 (d, J = 7.6 Hz, 2H), 6.85 (dq, J = 14.8, 7.3 Hz, 1H), 6.11 (d, J =
15.5 Hz, 1H), 3.86 (s, 1H), 2.51−2.41 (m, 2H), 1.85 (d, J = 6.9 Hz,
3H), 1.75 (s, 6H), 1.17 (d, J = 7.2 Hz, 3H); 13C NMR (126 MHz,
CDCl3) δ 209.3, 201.5, 170.7, 143.5, 142.4, 136.4, 130.5, 129.0 (2C),
127.9 (2C), 127.1, 58.4, 53.0, 44.5, 18.4, 15.6, 15.5, 8.4; IR (thin film)
1710, 1650 cm−1; HRMS (ESI) calcd for [C19H22O2Na]+ 305.1512,
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J. Org. Chem. XXXX, XXX, XXX−XXX

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