Novel synthesis of a highly functionalized cyclopropane derivative

Article abstract of DOI:10.1139/v03-119

A model study was carried out to explore the feasibility of synthesizing fused tricyclic ring structures containing a C₇-C₈ double bond juncture (steroid numbering) by employing an S_N2′ cyclization of a silyl enol ether to displace an allylic acetate as the key step. Instead of the anticipated product, highly functionalized cyclopropanes were obtained. These novel cyclopropane structures are the result of the concomitant 1,2-migration of a dithiane thioether moiety and the eventual displacement of the acetate group, followed by the cyclization of the silyl enol ether.

Full text of DOI:10.1139/v03-119

1003
Novel synthesis of a highly functionalized
cyclopropane derivative
Stéphane Trudeau and Pierre Deslongchamps
Abstract: A model study was carried out to explore the feasibility of synthesizing fused tricyclic ring structures con-
taining a C7—C8 double bond juncture (steroid numbering) by employing an SN2′ cyclization of a silyl enol ether to
displace an allylic acetate as the key step. Instead of the anticipated product, highly functionalized cyclopropanes were
obtained. These novel cyclopropane structures are the result of the concomitant 1,2-migration of a dithiane thioether
moiety and the eventual displacement of the acetate group, followed by the cyclization of the silyl enol ether.
Key words: tricycles, SN2′ cyclization, inductive effect, cyclopropane.
Résumé : Une étude modèle a été réalisée pour vérifier la possibilité de produire des tricycles possédant une double
liaison entre les carbones C7 et C8 (numérotation des stéroïdes) par une réaction de cyclisation SN2′ entre un éther
d’énol silylé et un acétate allylique comme étape clé. Or, une réaction inattendue s’est produite pour conduire à la syn-
thèse de cyclopropanes hautement fonctionnalisés au lieu du produit attendu. Cela étant le résultat d’une cyclisation
entre un éther d’énol silylé sur un groupement dithiane où l’un des thioéthers a subi une migration-1,2 tout en dépla-
çant le groupement acétate partant.
Mots clés : tricycles, cyclisation SN2′, effet inductif, cyclopropane.
Trudeau and Deslongchamps 1011
Introduction
carvone. Thus, Michael addition of phenylthiomethyl phenyl
sulfone (2, 3) and trapping of the attendant enolate with tert-
butyldimethylsilyl trifluoromethanesulfonate furnished thio-
ether 4 (Scheme 1). It is noteworthy that the presence of the
thioether moiety in the nucleophile was necessary to achieve
exclusive 1,4-addition. Thioether 4 was then subjected to n-
Bu3SnH–AIBN reduction in refluxing benzene to obtain
sulfone 5. Deprotonation of sulfone 5 with n-BuLi, followed
by alkylation with the commercially available reagent, 1-
cyclohexene-1-carboxaldehyde, afforded the alcohol 6. The
latter product was then acylated with acetic anhydride and
catalytic DMAP in pyridine to yield the acetate 7. All at-
tempts to procure the ABC-fused tricyclic structure, 8, using
the acetate 7 were in vain. For instance, in protic acidic me-
dium, Lewis acid medium, or under anionic conditions, only
deprotection of the silyl enol ether was observed. Even with
palladium, the formation of the π-allyl palladium species
was not observed, and only starting material was recovered
instead. It may therefore be concluded that the inductive ef-
fect of the sulfonyl group prohibits the solvolysis of the ace-
tate, thus precluding the formation of the π-allyl cation that
would have been trapped by the silyl enol ether.
More than 25 years ago, Nozaki and co-workers (1) stud-
ied cationic cyclization of allylic acetates via nucleophilic
participation of silyl enol ether. In light of this study, we re-
cently conducted a model study to investigate the possibility
of using an SN2′-type cyclization of a silyl enol ether to dis-
place an allylic acetate to generate C7–C8 (steroid number-
ing) unsaturated fused tricyclic ring structures (cf. 1, Fig. 1).
In model structures containing a sulfone moiety (X = SO2Ph,
Y = H) or a methylene group (X = Y = H) next to the ace-
tate leaving group no cyclization occurred. In contrast, when
the model compound was decorated with a dithiane func-
tionality (X, Y = S-(CH2)3-S) adjacent to the acetate leaving
group, instead of obtaining the anticipated product 1
(Fig. 1), the unexpected formation of a highly functionalized
cyclopropane was observed (cf. 2, Fig. 1). The details of this
investigation are disclosed herein.
Results and discussion
The use of a sulfone connector for the coupling of rings A
and C was explored initially. The intermediate 7 was synthe-
sized starting from the commercially available (R)-(–)-
To circumvent the obstacle encountered with the sulfonyl
group, alcohol 6 was oxidized with TPAP–NMO in dichloro-
methane in the presence of 4 Å molecular sieves to produce
the ketosulfone 9 (Scheme 2). Subsequent desulfurization
with n-Bu3SnH–AIBN in refluxing toluene yielded ketone
10 (4), which was immediately converted to the correspond-
ing alcohol using Luche reduction conditions (NaBH4–CeCl3
in methanol). The alcohol thus obtained was then acylated
with acetic anhydride – DMAP (catalytic) in pyridine to ob-
tain the acetate 11. To our dismay, all efforts directed at ef-
fecting cyclization of the precursor acetate 11 to form 12
Received 28 February 2003. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 29 August 2003.
S. Trudeau and P. Deslongchamps.1 Laboratoire de synthèse
organique, Département de Chimie, Institut de Pharmacologie
de Sherbrooke, Université de Sherbrooke, 3001, 12e Avenue
nord, Sherbrooke, QC J1H 5N4, Canada.
1Corresponding author (e-mail:
pierre.deslongchamps@usherbrooke.ca).
Can. J. Chem. 81: 1003–1011 (2003)
doi: 10.1139/V03-119
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Can. J. Chem. Vol. 81, 2003
Scheme 1. (a) i. Phenylsulfonylphenylthiomethane, n-BuLi, THF; ii. (R)-(–)-carvone; iii. TBS-OTf, Et3N (quant.); (b) n-Bu3SnH,
AIBN, PhH (87%); (c) i. n-BuLi, THF; ii. 1-cyclohexene-1-carboxaldehyde (61%); (d) Ac2O, DMAP, pyridine (92%).
Scheme 2. (a) TPAP, NMO, MS 4A, CH2Cl2 (60%); (b) n-Bu3SnH, AIBN, toluene (quant.); (c) NaBH4, CeCl3, MeOH (79%);
(d) Ac2O, DMAP, pyridine (86%).
Fig. 1. Target structures.
SN2′ coupling with silyl enol ether in the presence of a
Lewis acid. Keeping this in mind, the synthesis of acetate 17
was then undertaken, starting from the commercially avail-
able 1,3-dithiane 13 (Scheme 3). Deprotonation of the latter
with LDA and trapping of the attendant anion with n-
Bu3SnCl furnished stannane 14 in quantitative yield (6).
Deprotonation of intermediate 14 with LDA followed by a
1,4-Michael addition with (R)-(–)-carvone and trapping of
the resultant enolate with tert-butyldimethylsilyl trifluoro-
methanesulfonate in the presence of triethylamine yielded
compound 15. Transmetallation of the stannyl moiety in 15
with n-BuLi, followed by alkylation with 1-cyclohexene-1-
carboxaldehyde, afforded alcohol 16 in a 3:1 diastereomeric
ratio. The alcohol 16 was then acylated with acetic anhy-
dride – DMAP (catalytic) in pyridine to provide the acetate
17 (3:1 diastereomeric mixture). With acetate 17 in hand, a
preliminary attempt was made to induce the SN2′ cyclization
using p-TSA in benzene. The neighboring group participa-
tion induced by the dithiane helped the departure of the ace-
tate group, furnishing compound 18 in 64% yield. Thus,
were unsuccessful. Exclusive deprotection of the silyl enol
ether occurred in most cases (acidic medium as well as an-
ionic conditions). With palladium species, only starting ma-
terial was recovered. On the basis of the above studies, it
can be concluded that even in absence of the inductive effect
of the sulfonyl group, the acetate group is reluctant to leave
and thereby induce cyclization.
Recently, Saigo and co-workers (5) reported that allylic
acetates with a thioether as a neighboring group can undergo
© 2003 NRC Canada

Trudeau and Deslongchamps
1005
Scheme 3. (a) i. LDA, THF; ii. n-Bu3SnCl (quant.); (b) i. LDA, THF; ii. (R)-(–)-carvone, HMPA; iii. TBS-OTf, Et3N (88%); (c) i. n-
BuLi, THF ii. 1-cyclohexene-1-carboxaldehyde (75%) (ratio of diastereoisomers = 3:1); (d) Ac2O, DMAP, pyridine (79%); (e) p-TSA,
PhH (64%); (f) TMS-OTf, CH2Cl2 (77%) (ratio 2a:2b:18:19 = 3:1:1.2:1.5); (g) LiAlH4, THF (71%) (ratio of diastereoisomers = 7.5:1);
(h) 4-nitrobenzoyl chloride, DMAP, pyridine, CH2Cl2 (40%).
hydrogen abstraction and formation of a double bond in-
duced a net 1,2-migration of a thioether. The structure of
compound 18 was assigned by spectral analysis, including
DEPT NMR studies. A similar 1,2-migration of a thioether
has also been recently reported by Kutateladze and co-
workers (7).
We next explored the possibility of effecting the SN2′
cyclization under Lewis acid conditions. To our great sur-
prise, however, when acetate 17 was treated with trimethyl-
silyl trifluoromethanesulfonate in dichloromethane at –78 °C,
cyclopropane 2 was obtained in 46% yield as a separable 3:1
mixture of two diastereoisomers. Compounds 18 and 19
were also isolated from the reaction mixture (14% and 17%
yield, respectively). Again, it can be surmised that the
dithiane facilitated the departure of the acetate group in
compounds 17a and 17b to form intermediate 21a and 21b
as sulfonium cations (Fig. 2). These sulfonium cations could
then rearrange to intermediates 22a and 22b and, thereby,
induce a net 1,2-migration of a thioether moiety. Thus, the
silyl enol ether participates in a C—C bond formation at C6
in a Mukaiyama thio-aldol fashion instead of promoting
cyclization at C9 in an SN2′ manner, contrary to our initial
expectations. Moreover, it can be presumed that the
Mukaiyama thio-aldol process was stereoselective, as the
diastereoisomeric composition in cyclopropane products was
identical to that in the acetate starting material. The structure
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Can. J. Chem. Vol. 81, 2003
Fig. 2. Proposed mechanism for formation of cyclopropanes 2a and 2b.
of the major diastereoisomer 2a was assigned by single-
crystal X-ray diffraction crystallography of the benzoate 20
(Fig. 3).2 This product was prepared from compound 2a,
which was reduced with LiAlH4 in THF to give two dias-
tereoisomers (7.5:1) that were readily separable by flash
chromatography on silica gel. The major diastereoisomer
was subsequently acylated, using 4-nitrobenzoyl chloride –
DMAP (catalytic) – pyridine in dichloromethane, to provide
20.
0.75 h, and then triethylamine (1.2 mL, 8.7 mmol) was
added. The mixture was warmed to room temperature,
stirred for 0.15 h, poured into a saturated aqueous solution
of NaHCO3 (30 mL), and extracted with ether (3 × 30 mL).
The combined organic phases were washed with brine
(100 mL), dried with MgSO4, filtered, and concentrated un-
der reduced pressure. The crude product was purified by
flash chromatography (hexane–ether 8:2) to give the thio-
ether 4 (0.97 g, quantitative) as a pale yellow oil (mixture of
diastereoisomers). [α]D = +63.51° (c 1.71, CHCl3). IR
(film, cm–1) ν: 3476, 3063, 2955, 2857, 1710, 1583, 1472,
1448, 1307, 1255, 1148, 1083, 836, 741, 688. 1H NMR
(300 MHz, CDCl3, ppm) δ: 7.92 (2H, m, H arom. ortho to
SO2R), 7.58 (1H, m, H arom. para to SO2R), 7.46 (2H, m, H
arom. meta to SO2R), 7.14 (2H, m, H arom. ortho to SR),
7.07 (2H, m, H arom. meta to SR), 6.96 (1H, m, H arom.
para to SR), 4.73 and 4.64 (2H, 2d, J = 17.9 and 35.5 Hz,
(CH3)C=CH2), 4.30 (1H, dd, J = 37.0 and 2.0 Hz, PhSO2-
CH-SPh), 3.29 (1H, m), 3.00 (1H, m), 2.38–1.78 (4H, m),
1.77 and 1.63 (3H, 2s, (CH3)C=CH2), 1.60 and 1.42 (3H, 2s,
TBSO-C=C-CH3), 0.95 (9H, m, (CH3)3-C-Si), 0.13 (6H, m,
(CH3)2-Si). 13C NMR (75 MHz, CDCl3, ppm) δ: 148.1,
147.9, 147.1, 138.4, 137.7, 134.3, 133.7, 133.6, 132.3,
131.8, 129.8, 129.4, 129.1, 129.0, 128.8, 127.9, 112.8,
111.0, 109.5, 109.3, 107.8, 105.2, 80.2, 76.4, 39.9, 38.2,
37.8, 37.7, 36.2, 35.4, 34.4, 28.7, 27.2, 26.0, 25.8, 25.8,
25.6, 22.6, 21.2, 20.2, 18.2, 18.0, 16.6, 14.2, –3.5, –3.6. EI-
MS: 528 ([M]+). HR-MS ([M]+) calcd. for C29H40O3S2Si:
528.2188; found: 528.2184.
Experimental
General
All reactions were performed under N2 atmosphere with
flame-dried glassware. Solvents were distilled and dried ac-
cording to standard procedures. Analytical TLC were per-
formed on precoated glass plates (0.25 mm) with silica gel
60F-250 (Merck). Flash-chromatography was performed
1
with 230–400 mesh gel 60 (Merck). H and 13C NMR spec-
tra were recorded on a Brüker AC-300 and are referenced
with respect to the residual signals of the solvent; they are
described using standard abbreviations. IR spectra were re-
corded on a PerkinElmer 1600 FT-IR. Mass spectra were re-
corded on a ZAB-1F micromass spectrometer.
Thioether (4)
To a solution of phenylthiomethyl phenyl sulfone (2, 3)
(0.55 g, 2.1 mmol) in THF (27.0 mL) cooled to –78 °C was
added n-butyllithium (1.24 mol·L–1 in hexane) (1.7 mL,
2.1 mmol). The solution was stirred for 1 h at –78 °C, then
(R)-(–)-carvone (0.26 g, 1.7 mmol) in THF (6.0 mL) was
added. The mixture was stirred for 2 h at –78 °C before tert-
butyldimethylsilyl trifluoromethanesulfonate (1.2 mL,
5.2 mmol) was added. The mixture was stirred for another
Sulfone (5)
To a solution of thioether 4 (1.1 g, 2.0 mmol) in benzene
(52.0 mL) was added tributyltin hydride (1.1 mL, 4.3 mmol)
and AIBN (0.033 g, 0.20 mmol). N2 was bubbled for 0.1 h
2 Crystallographic data (excluding structure factors) for the structures in this paper have been deposited. Supplementary data may be pur-
chased from the Depository of Unpublished Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0S2,
Canada (http://www.nrc.ca/cisti/irm/unpub_e.shtml for information on ordering electronically). CCDC 200815 contain the supplementary
data for this paper. These data can be obtained, free of charge, via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crys-
tallographic Data Centre, 12 Union Road, Cambridge, U.K.; fax +44 1223 336033; or deposit@ccdc.cam.ac.uk).
© 2003 NRC Canada

Trudeau and Deslongchamps
1007
Fig. 3. Single-crystal X-ray structure of cyclopropane 20.
into the solution to exclude O2. The solution was then heated
at reflux for 2 h, cooled to room temperature, and concen-
trated under reduced pressure. The crude product was puri-
fied by flash chromatography (hexane–ether 9:1) to give the
sulfone 5 (0.69 g, 87%) as a clear oil. [α]D = +26.56° (c
1.51, CHCl3). IR (film, cm–1) ν: 2930, 2858, 1683, 1472,
and extracted with ether (3 × 5 mL). The combined organic
phases were washed with brine (15 mL), dried with MgSO4,
filtered, and concentrated under reduced pressure. The crude
product was purified by flash chromatography (hexane–ether
9:1 to 7:3) to give the alcohol 6 (0.095 g, 61%) as a pale
yellow oil (mixture of diastereoisomers). [α]D = +34.76° (c
1.03, CHCl3). IR (film, cm–1) ν: 3491, 2931, 2858, 1682,
1447, 1302, 1176, 1140, 1083, 1056, 913, 834, 731. 1H
NMR (300 MHz, CDCl3, ppm) δ: 7.89 (2H, m, H arom.
ortho to SO2R), 7.53 (3H, m, H arom. meta and para to
SO2R), 5.77 (1H, s, HC=C-CH-OH), 4.71 (2H, d, J =
33.5 Hz, (CH3)C=CH2), 4.66 (1H, d, J = 12.5 Hz, CH-OH),
3.70 (1H, dd, J = 8.5 and 3.0 Hz, CH-SO2Ph), 3.00 (1H, d,
J = 4.5 Hz, CH-OH), 2.56 (2H, s), 2.26 (2H, m), 2.00
(4H, m, CH2-CH=C-CH2), 1.78 (1H, qu, J = 6.5 Hz), 1.71
(3H, s, (CH3)C=CH2), 1.63 (1H, m), 1.55 (3H, s, TBSO-
C=C-CH3), 1.46 (4H, m, CH2-CH2-CH=C-CH2-CH2), 0.94
1
1447, 1306, 1253, 1197, 1150, 1087, 1064, 929, 837. H
NMR (300 MHz, CDCl3, ppm) δ: 7.93 (2H, m, H arom.
ortho to SO2R), 7.61 (3H, H arom. meta and para to SO2R),
4.71 (3H, d, J = 17.0 Hz, (CH3)C=CH2), 3.10 (2H, m, -CH2-
SO2Ph), 2.64 (1H, s), 2.21 (1H, m), 2.00 (3H, m), 1.69
(3H, s, (CH3)C=CH2), 1.49 (1H, td, J = 13.0 and 5.0 Hz),
1.40 (3H, s, TBSO-C=C-CH3)), 0.91 (9H, s, (CH3)3-C-Si),
0.08 (6H, s, (CH3)2-Si). 13C NMR (75 MHz, CDCl3, ppm) δ:
147.9, 145.7, 139.6, 133.6, 129.3, 128.0, 110.9, 109.7,
105.2, 58.1, 37.0, 35.3, 34.7, 31.3, 25.7, 20.8, 18.2, 14.2,
–3.7, –3.8. EI-MS: 420 ([M]+). HR-MS ([M]+) calcd. for
C23H36O3SSi: 420.2154; found: 420.2151.
(9H, s, (CH3)3-C-Si), 0.15 (6H, d, J = 10 Hz, (CH3)2-Si). 13
C
NMR (75 MHz, CDCl3, ppm) δ: 147.2, 144.5, 142.9, 136.3,
133.0, 128.6, 128.1, 127.7, 109.6, 109.4, 75.9, 67.9, 37.7,
37.7, 34.2, 28.0, 25.8, 25.1, 22.9, 22.2, 22.1, 21.7, 18.1,
14.5, –3.6. EI-MS: 530 ([M]+). HR-MS ([M]+) calcd. for
C30H46O4SSi: 530.2886; found: 530.2894.
Alcohol (6)
To a solution of sulfone 5 (0.14 g, 0.32 mmol) in THF
(2.0 mL) at –78 °C was added n-butyllithium (1.24 mol·L–1
in hexane) (0.26 mL, 0.32 mmol). The solution was stirred
for 1 h at –78 °C and then 1-cyclohexene-1-carboxaldehyde
(0.033 mL, 0.29 mmol) was added. The mixture was stirred
for 2.5 h and was slowly warmed to –50 °C. It was then
poured into a saturated aqueous solution of NH4Cl (4 mL)
Acetate (7)
Acetic anhydride (0.068 mL, 0.72 mmol) and DMAP
(0.012 g, 0.10 mmol) were added to a solution of the alcohol
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Can. J. Chem. Vol. 81, 2003
6 (0.26 g, 0.48 mmol) in pyridine (5.0 mL). The solution
was stirred for 2 h at room temperature, neutralized with
HCl 1 N (5 mL) at 0 °C, and extracted with ethyl acetate
(3 × 5 mL). The organic phase was washed with brine
(20 mL), dried with MgSO4, filtered, and concentrated under
reduced pressure. The crude product was purified by flash
chromatography (hexane–ether 8:2 to 7:3) to yield acetate 7
(0.25 g, 92%) as a clear oil (mixture of diastereoisomers).
[α]D = +13.98° (c 1.18, CHCl3). IR (film, cm–1) ν: 2930,
2858, 1747, 1682, 1447, 1306, 1229, 1177, 1144, 913, 832,
730. 1H NMR (300 MHz, CDCl3, ppm) δ: 7.80 (2H, dd, J =
8.0 and 1.2 Hz, H arom. ortho to SO2R), 7.52 (3 H, m, H
arom. meta and para to SO2R), 5.91 (1H, s, CH=C-(C=O)),
5.74 (1H, d, J = 10.1 Hz, CH-OAc), 4.72 (2H, d, J =
30.5 Hz, (CH3)C=CH2), 4.00 (1H, dd, J = 10.1 and 2.2 Hz,
CH-SO2Ph), 2.64 (1H, m), 2.57 (1H, m), 2.42–2.24 (2H, m),
2.00 (4H, m, CH2-CH2-CH=C-CH2-CH2), 1.85 (1H, m),
1.80 (3H, s, CH-O(C=O)-CH3), 1.74 (1H, m), 1.71 (3H, s,
(CH3)C=CH2), 1.50 (4H, m, CH2-CH=C-CH2), 1.43 (3H, s,
TBSO-C=C-CH3), 0.95 (9H, m, (CH3)3C-Si), 0.17 (6H, d,
J = 10.0 Hz, (CH3)2Si). 13C NMR (75 MHz, CDCl3, ppm)
δ: 168.6, 147.2, 144.0, 143.8, 132.7, 132.1, 131.5, 128.9,
126.9, 109.9, 109.4, 77.8, 64.1, 37.6, 37.1, 34.4, 26.9, 25.9,
25.1, 22.8, 22.1, 21.9, 20.8, 18.1, 14.2, –3.7, –3.8. EI-MS:
572 ([M]+). HR-MS ([M]+) calcd. for C32H48O5SSi:
572.2992; found: 572.3000.
2.16 mmol). N2 was bubbled for 5 min into the solution to
exclude O2. The solution was then heated at reflux, and
AIBN (0.060 g, 0.37 mmol) was added. The solution was
heated at reflux 5 min, and then a second portion of AIBN
(0.037 g, 0.12 mmol) was added. The solution was heated at
reflux another 10 min, cooled to room temperature, and con-
centrated under reduced pressure. The crude product was pu-
rified by flash chromatography (hexane–ether 10:0 to 8:2) to
give the enone 10 (0.23 g, quantitative) as a clear liquid.
[α]D = +19.46° (c 1.12, CHCl3). IR (film, cm–1) ν: 2929,
1
2858, 1661, 1463, 1378, 1252, 1174, 1072, 926, 837. H
NMR (300 MHz, CDCl3, ppm) δ: 6.89 (1H, m, CH=C-
(C=O)), 4.71 (2H, m, (CH3)C=CH2), 2.69 (2H, s, CH2-
(C=O)), 2.32 (1H, m), 2.24 (4H, m), 2.03 (1H, m), 1.70
(3H, s, (CH3)C=CH2), 1.76–1.24 (8H, m), 1.50 (3H, s,
TBSO-C=C-CH3), 0.95 (9H, m, (CH3)3C-Si), 0.13 (6H, s,
(CH3)2Si). 13C NMR (75 MHz, CDCl3, ppm) δ: 201.2,
148.9, 143.9, 139.7, 113.7, 109.0, 40.0, 37.4, 35.8, 35.6,
31.9, 27.8, 26.8, 26.1, 25.8, 23.2, 22.0, 21.5, 17.5, 13.6,
–3.7, –3.9. EI-MS: 388 ([M]+). HR-MS ([M]+) calcd. for
C24H40O2Si: 388.2797; found: 388.2801.
Acetate (11)
Sodium borohydride (0.012 g, 0.32 mmol) was dissolved
in methanol (0.50 mL), and the mixture was cooled to 0 °C.
To this mixture was added dropwise a solution of cerium
(III) chloride heptahydrate (0.12 g, 0.32 mmol) and ketone
10 (0.11 g, 0.29 mmol) in methanol (0.94 mL). The mixture
was stirred for 0.5 h at 0 °C and 0.5 h at room temperature.
It was cooled back to 0 °C, and a saturated aqueous solution
of NH4Cl (2 mL) was added. The mixture was extracted
with dichloromethane (3 × 3 mL). The combined organic
phases were washed with brine (10 mL), dried with MgSO4,
filtered, and concentrated under reduced pressure. The crude
product was purified by flash chromatography (hexane–ether
95:5 to 9:1) to give the alcohol (0.089 g, 79%) as a colorless
liquid (mixture of diastereoisomers). [α]D = +14.22° (c 1.16,
CHCl3). IR (film, cm–1) ν: 3350, 2929, 2858, 1682, 1645,
1448, 1256, 1178, 922, 889, 837, 779, 735. 1H NMR
(300 MHz, CDCl3, ppm) δ: 5.65 (1H, d, J = 3.5 Hz, CH=C-
(C=O)), 4.72 (2H, d, J = 0.45 Hz, (CH3)C=CH2), 4.08–3.97
(1H, m, CH-OH), 2.40–1.35 (16H, m), 1.74 (3H, s,
(CH3)C=CH2), 1.59 (3H, s, TBSO-C=C-CH3), 0.93 (9H, s,
(CH3)3C-Si), 0.10 (6H, d, J = 1.1 Hz, (CH3)2Si). 13C NMR
(75 MHz, CDCl3, ppm) δ: 149.2, 143.3, 143.1, 140.7,
139.2, 124.8, 122.1, 114.8, 114.4, 108.9, 108.8, 76.3, 74.5,
38.1, 37.3, 37.2, 36.9, 36.2, 35.7, 35.7, 35.5, 31.6, 31.4,
30.9, 25.9, 25.1, 24.9, 24.0, 22.6, 22.5, 20.7, 18.2, 15.1,
14.9, –3.7, –3.8, –3.8, –3.9. EI-MS: 390 ([M]+). HR-MS
([M]+) calcd. for C24H42O2Si: 390.2954; found: 390.2951.
Ketosulfone (9)
To a solution of alcohol 6 (0.49 g, 0.92 mmol) in di-
chloromethane (9.2 mL) was added 4 Å molecular sieves
(0.92 g), 4-methylmorpholine N-oxide (0.22 g, 1.9 mmol),
and tetrapropylammonium
perruthenate
(0.032 g,
0.090 mmol). The mixture was stirred for 0.5 h at room tem-
perature, and the solvent was then concentrated under re-
duced pressure. Ether (10 mL) was added, and the mixture
was filtered through a silica gel pad. The pad was rinsed
with ether (10 mL), and the combined flitrates were concen-
trated under reduced pressure. The crude product was puri-
fied by flash chromatography (hexane–ether 9:1 to 7:3) to
give the ketosulfone 9 (0.30 g, 60%) as a pale yellow oil.
[α]D = +78.64° (c 1.03, CHCl3). IR (film, cm–1) ν: 2931,
2859, 1663, 1633, 1448, 1321, 1255, 1196, 1146, 1083, 921,
1
840. H NMR (300 MHz, CDCl3, ppm) δ: 7.89 (2H, m, H
arom. ortho to SO2R), 7.57 (1H, m, H arom. para to SO2R),
7.47 (2H, m, H arom. meta to SO2R), 6.70 (1H, t, J =
4.0 Hz, CH=C-(C=O)), 4.96 (1H, d, J = 10.1 Hz, CH-
SO2Ph), 4.79 (2H, m, (CH3)C=CH2), 3.11 (1H, m), 2.69
(1H, m), 2.61 (1H, d, J = 13.6 Hz), 2.12 (6H, m), 1.79
(3H, s, (CH3)C=CH2), 1.58 (1H, td, J = 13.0 and 4.4 Hz),
1.42 (4H, m, CH2-CH=C-CH2), 1.25 (3H, s, TBSO-C=C-
CH3), 0.88 (9H, s, (CH3)3C-Si), 0.04 (6H, d, J = 12.6 Hz,
(CH3)2Si). 13C NMR (75 MHz, CDCl3, ppm) δ: 193.2,
148.2, 147.5, 142.6, 140.5, 138.7, 133.6, 129.9, 128.6,
111.6, 109.6, 70.7, 41.2, 37.0, 35.1, 31.1, 26.3, 25.7, 23.2,
21.5, 21.1, 20.5, 18.1, 17.4, –3.7, –3.8. EI-MS: 528 ([M]+).
HR-MS ([M]+) calcd. for C30H44O4SSi: 528.2729; found:
528.2722.
Acetic anhydride (0.032 mL, 0.34 mmol) and DMAP
(5.5 mg, 0.050 mmol) were added to a solution of the alco-
hol (0.088 g, 0.23 mmol) of the preceding reaction in
pyridine (2.3 mL). The solution was stirred for 3 h at room
temperature, neutralized with an aqueous solution of HCl
1 N (5 mL), and extracted with ethyl acetate (3 × 5 mL).
The organic phase was washed with brine (15 mL), dried
with MgSO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by flash chromatogra-
phy (hexane–ether 97:3) to yield acetate 11 (0.083 g, 86%)
Ketone (10)
To a solution of ketosulfone 9 (0.29 g, 0.54 mmol) in tolu-
ene (5.4 mL) was added tributyltin hydride (0.58 mL,
as a colorless liquid (mixture of diastereoisomers). [α]D
=
© 2003 NRC Canada

Trudeau and Deslongchamps
1009
+10.10° (c 1.00, CHCl3). IR (film, cm–1) ν: 2927, 1738,
of n-butyllithium (1.35 mol·L–1 in hexane) (1.3 mL,
1.8 mmol) was added dropwise. The solution was stirred for
0.5 h at –100 °C, and a solution of 1-cyclohexene-1-car-
boxaldehyde (0.33 mL, 2.9 mmol) in THF (15.0 mL) was
added via canula. The solution was stirred for 1.25 h at
–100 °C, brought to 0 °C, neutralized with a saturated aque-
ous solution of NH4Cl (20 mL), and extracted with ether
(3 × 25 mL). The combined organic phases were washed
with brine (50 mL), dried with MgSO4, filtered, and concen-
trated under reduced pressure. The crude product was puri-
fied by flash chromatography (hexane–ether 100:0 to 95:5)
to give alcohol 16 (0.33 g, 75%) as a clear oil (mixture of
diastereoisomers, ratio = 3:1). [α]D = +10.50° (c 1.14,
CHCl3). IR (film, cm–1) ν: 3444, 2929, 2857, 1667, 1644,
1252, 1192, 927, 837, 780, 734. 1H NMR (300 MHz,
CDCl3, ppm) δ: 6.00 (1H, s, CH=C-CH-OH), 4.73 (2H, m,
(CH3)C=CH2), 4.51 (1H, m, CH-OH), 3.29–1.34 (15H, m),
1.80 (3H, d, J = 9.3 Hz, TBSO-C=C-CH3), 1.75 (3H, d, J =
4.3 Hz, (CH3)C=CH2), 1.61 (4H, m), 1.40 (1H, tt, J = 13.1
and 4.8 Hz), 0.95 (9H, d, J = 1.7 Hz, (CH3)3C-Si), 0.16
(6H, s, (CH3)2Si). 13C NMR (75 MHz, CDCl3, ppm) δ:
149.4, 149.3, 148.8, 136.8, 136.4, 127.4, 127.1, 111.9,
111.5, 108.8, 108.7, 78.1, 76.4, 62.1, 61.9, 45.1, 43.0, 38.2,
37.4, 35.3, 35.1, 31.9, 31.8, 28.8, 28.5, 28.5, 27.8, 27.4,
27.2, 25.9, 25.9, 25.5, 24.4, 24.1, 23.1, 23.1, 22.4, 22.1,
20.5, 20.4, 19.5, 18.9, –3.2, –3.3, –3.4. EI-MS: 476 ([M –
H2O]+); 437 ([M – C4H9]+). HR-MS ([M – H2O]+) calcd.
for C27H44OS2Si: 476.2603; found: 476.2596.
1682, 1645, 1448, 1371, 1236, 1180, 1017, 922, 838, 780,
1
734. H NMR (300 MHz, CDCl3, ppm) δ: 5.69 (1H, d, J =
13.7 Hz, CH=C-CH-OAc), 5.15 (1H, m, CH-OAc), 4.72
(2H, s, (CH3)C=CH2), 2.38–2.28 (1H, m), 2.02 (3H, d, J =
11.2 Hz, CH-O-(C=O)-CH3), 1.99–1.34 (15H, m), 1.73 (3H,
d, J = 5.9 Hz, (CH3)C=CH2), 1.58 (3H, d, J = 5.5 Hz,
TBSO-C=C-CH3), 0.93 (9H, m, (CH3)3C-Si), 0.10 (6H, m,
(CH3)2Si). 13C NMR (75 MHz, CDCl3, ppm) δ: 170.5,
170.3, 149.0, 148.9, 143.5, 143.4, 136.4, 135.1, 126.5,
125.9, 124.3, 123.8, 114.2, 114.0, 110.5, 110.4, 109.0,
108.9, 105.2, 78.2, 76.3, 40.0, 39.4, 38.9, 37.3, 37.2, 36.4,
36.1, 35.9, 35.6, 35.6, 34.4, 31.1, 30.9, 25.8, 25.0, 24.9,
24.8, 23.3, 22.4, 21.4, 21.3, 20.8, 20.7, 18.2, 15.0, 14.8,
–3.7, –3.9. EI-MS: 432 ([M]+). HR-MS ([M]+) calcd. for
C26H44O3Si: 432.3060; found: 432.3063.
Stannane (15)
Tributyl-[1,3]dithian-2-yl-stannane 14 (1.2 g, 2.9 mmol)
was dried via azeotropic removal of water with benzene (3 ×
3 mL) and was then dissolved in THF (2.5 mL) and cooled
to –30 °C. In another flask, diisopropylamine (0.40 mL,
2.9 mmol) was dissolved in THF (2.5 mL), cooled to 0 °C,
and a solution of n-butyllithium (1.35 mol·L–1 in hexane)
(2.0 mL, 2.7 mmol) was added dropwise. The solution was
stirred for 0.25 h at 0 °C, cooled down to –30 °C, and trans-
ferred via canula to the first solution containing the
stannane. The mixture was stirred for 3 h at –30 °C and
cooled to –78 °C; HMPA (1.0 mL, 5.7 mmol) was added,
and the mixture was stirred for another 0.5 h. A solution of
(R)-(–)-carvone (0.20 g, 1.3 mmol) in THF (1.5 mL) pre-
cooled to –78 °C was transferred via canula to the mixture,
which was stirred for 1.25 h at –78 °C before tert-butyl-
dimethylsilyl trifluoromethanesulfonate (0.60 mL, 2.6 mmol)
was added. The mixture was stirred for 0.25 h at –78 °C,
triethylamine (0.55 mL, 3.9 mmol) was added, and the mix-
ture was warmed at room temperature and stirred for 0.5 h.
Water (10 mL) was added, and the mixture was extracted
with ether (3 × 10 mL). The combined organic phases were
washed with brine (25 mL), dried with MgSO4, filtered, and
concentrated under reduced pressure. The crude product was
purified by flash chromatography (hexane) to give the
stananne 15 (0.78 g, 88%) as a colorless oil. [α]D = +28.14°
(c 1.13, CHCl3). IR (film, cm–1) ν: 2956, 2856, 1667, 1463,
Acetate (17)
Acetic anhydride (0.27 mL, 2.9 mmol) and DMAP
(71.0 mg, 0.58 mmol) were added to a solution of the alco-
hol 16 (0.79 g, 0.58 mmol) in pyridine (5.8 mL). The solu-
tion was stirred for 4 h at room temperature, neutralized
with HCl 1 N (5 mL), and extracted with ethyl acetate (3 ×
10 mL). The organic phase was washed with brine (15 mL),
dried with MgSO4, filtered, and concentrated under reduced
pressure. The crude product was purified by flash chroma-
tography (hexane–ether 95:5) to give acetate 17 (0.24 g,
79%) as a colorless oil (mixture of diastereoisomers, ratio =
3:1). [α]D = +9.56° (c 1.13, CHCl3). IR (film, cm–1) ν: 2929,
2857, 1742, 1667, 1438, 1368, 1230, 1170, 1019, 926, 837,
1
780, 733. H NMR (300 MHz, CDCl3, ppm) δ: 5.94 (1H, s,
CH=C-CH-OAc), 5.76 (1H, d, J = 19.2 Hz, CH-OAc), 4.74
(2H, m, (CH3)C=CH2), 3.30–3.09 (2H,m), 2.98 (1H, m),
2.76 (1H, m), 2.64–2.46 (1H, m), 2.33–2.12 (3H, m), 2.08
(3H, d, J = 2.7 Hz, CH-O-(C=O)-CH3), 2.03–1.89 (1H, m),
1.84 (3H, d, J = 10.5 Hz, TBSO-C=C-CH3), 1.75 (3H, d, J =
3.8 Hz, (CH3)C=CH2), 1.26 (6H, m), 0.95 (9H, d, J =
1.0 Hz, (CH3)3C-Si), 0.16 (6H, t, J = 4.5 Hz, (CH3)2Si). 13C
NMR (75 MHz, CDCl3, ppm) δ: 169.5, 149.5, 149.4, 148.4,
134.9, 134.6, 129.5, 128.5, 111.7, 111.2, 108.8, 108.6, 82.4,
78.5, 59.7, 59.3, 45.7, 43.5, 37.7, 35.3, 35.1, 31.8, 31.7,
31.6, 28.8, 28.0, 27.7, 27.5, 27.4, 25.9, 25.4, 24.3, 24.2,
22.9, 22.6, 22.0, 22.0, 21.4, 20.5, 20.4, 19.8, 19.2, 18.2,
14.1, –3.3, –3.4. CI-MS: 537 ([MH]+). HR-MS ([MH]+)
calcd. for C29H49O3S2Si: 537.2892; found: 537.2887.
1
1252, 1194, 931, 837. H NMR (300 MHz, CDCl3, ppm) δ:
4.74 (2H, s, (CH3)C=CH2), 3.19 (1H, m), 3.13 (1H, m), 2.90
(1H, m), 2.69 (1H, m), 2.35–1.97 (8H, m), 1.94 (3H, s,
TBSO-C=C-CH3), 1.76 (3H, s, (CH3)C=CH2), 1.52 (6H, m,
Sn-(CH2-CH2-CH2-CH3)3), 1.33 (6H, m, Sn-(CH2-CH2-CH2-
CH3)3), 1.06 (6H, m, Sn-(CH2-CH2-CH2-CH3)3), 0.91
(18H, m, (CH3)3C-Si and Sn-(CH2-CH2-CH2-CH3)3), 0.14
(6H, s, (CH3)2-Si). 13C NMR (75 MHz, CDCl3, ppm) δ:
149.3, 145.4, 114.9, 108.7, 46.8, 36.6, 35.5, 34.0, 29.2, 27.6,
26.5, 25.9, 25.1, 25.0, 20.6, 18.7, 13.7, 10.1, –3.1, –3.3. EI-
MS: 617 ([M – C4H9]+). HR-MS ([M – C4H9]+) calcd. for
C28H53OS2SiSn: 617.2329; found: 617.2322.
Alcohol (16)
Ketone (18)
Stannane 15 (0.61g, 0.91 mmol) was dried via azeotropic
removal of water with benzene (3 × 10 mL); it was then dis-
solved in THF (10.0 mL), cooled to –100 °C, and a solution
Acetate 17 (0.026 g, 0.048 mmol) was dried via
azeotropic removal of water with benzene (3 × 1 mL) and
© 2003 NRC Canada

1010
Can. J. Chem. Vol. 81, 2003
then dissolved in benzene (1.0 mL), and p-toluenesulfonic
acid monohydrate (2.0 mg, 0.010 mmol) was added. The so-
lution was heated at reflux for 16 h, cooled to room temper-
ature, neutralized with a saturated aqueous solution of
NaHCO3 (3 mL), and extracted with ether (3 × 5 mL). The
organic phase was dried with MgSO4, filtered, and concen-
trated under reduced pressure. The crude product was puri-
fied by flash chromatography (hexane–ether 95:5) to give
ketone 18 (8.1 mg, 46%) as a yellow oil. [α]D = –72.35° (c
1.15, CHCl3). IR (film, cm–1) ν: 2929, 1708, 1448, 904, 733.
1H NMR (300 MHz, CDCl3, ppm) δ: 5.39 (1H, m, CH=C),
4.84 and 4.61 (2H, 2s, (CH3)C=CH2), 3.08–2.51 (9H, m),
2.18 (4H, m), 1.97 (2H, m), 1.77 (1H, dd, J = 13.7 and
2.7 Hz), 1.70 (3H, d, J = 0.6 Hz, (CH3)C=CH2), 1.63–1.47
(5H, m), 0.94 (3H, d, J = 6.5 Hz, (C=O)-C-CH3). 13C NMR
(75 MHz, CDCl3, ppm) δ: 212.6, 146.9, 141.0, 138.1, 137.9,
125.9, 112.4, 47.8, 45.9, 44.6, 41.0, 33.0, 32.4, 31.8, 31.4,
28.3, 25.1, 22.6, 22.5, 21.7, 12.5. EI-MS: 362 ([M]+). HR-
MS ([M]+) calcd. for C21H30OS2: 362.1738; found:
362.1729.
C21H30OS2: 362.1738; found: 362.1743. Compound 19:
[α]D = –41.06° (c 2.63, CHCl3). IR (film, cm–1) ν: 2929,
1708, 1438, 1414, 892, 754. H NMR (300 MHz, CDCl3,
1
ppm) δ: 5.45 (1H, m, CH=C), 4.74 (2H, d, J = 12.3 Hz,
C(CH3) = CH2), 3.55 (1H, m), 3.17 (2H, m), 2.92 (1H, m),
2.85 (1H, m), 2.77 (1H, m), 2.60 (1H, dd, J = 15.0 and
4.4 Hz), 2.36 (1H, qu, J = 6.5 Hz), 2.18 (3H, m), 2.05
(4H, m), 1.90 (2H, m), 1.72 (3H, s, (CH3)C=CH2), 1.71–
1.54 (4H, m), 1.06 (3H, d, J = 6.8 Hz, CH3-CH).13C NMR
(75 MHz, CDCl3, ppm) δ: 211.8, 147.9, 138.6, 128.3, 125.4,
112.4, 109.8, 47.2, 47.0, 45.3, 41.1, 36.6, 33.3, 32.5, 31.3,
28.4, 25.1, 22.7, 21.8, 20.6, 12.7. EI-MS: 362 ([M]+). HR-
MS ([M]+) calcd. for C21H30OS2: 362.1738; found: 362.1729.
Nitrobenzoate (20)
To a solution of cyclopropane 2a (0.024 g, 0.066 mmol)
in THF (1.3 mL) was added lithium aluminum hydride
(3.7 mg, 0.099 mmol). The solution was stirred for 15 min at
room temperature, neutralized with a dropwise addition of a
saturated aqueous solution of NH4Cl (5 mL), and extracted
with ether (3 × 5 mL). The organic phase was dried with
MgSO4, filtered, and concentrated under reduced pressure.
The crude product was purified by flash chromatography
(hexane–ether 100:0 to 98:2) to give the alcohol as the major
diastereoisomer (0.015 g, 63%) and the minor
diastereoisomer (2.0 mg, 8%). Major diastereoisomer: [α]D =
–173.82° (c 1.10, CHCl3). IR (film, cm–1) ν: 3788, 3492,
Cyclopropanes (2a and 2b)
Acetate 17 (0.35 g, 0.65 mmol) was dried via azeotropic
removal of water with benzene (3 × 10 mL) and then dis-
solved in dichloromethane (33.0 mL) and cooled to –78 °C.
Trimethylsilyl
trifluoromethanesulfonate
(0.12
mL,
0.65 mmol) was added slowly, and the solution was stirred
for 5 min before a saturated aqueous solution of NaHCO3
(25 mL) was added. The mixture was extracted with ether
(3 × 25 mL). The combined organic phases were washed
with brine (50 mL), dried with MgSO4, filtered, and concen-
trated under reduced pressure. The crude product was puri-
fied by flash chromatography (hexane–ether 95:5) to give
compound 19 (0.041 g, 17%), compound 18 (0.033 g, 14%),
and the cyclopropane 2 (0.11 g, 46%) as a mixture of two
diastereoisomers, which were separated by preparative TLC
(eluted 2 times with toluene) to give the major product 2a
(0.033 g) and the minor product 2b (0.011 g). Major product
2a: [α]D = –361.07° (c 1.40, CHCl3). IR (film, cm–1) ν:
1
2921, 1641, 1446, 1403, 1013, 885. H NMR (300 MHz,
CDCl3, ppm) δ: 6.46 (1H, s, CH=C), 4.79 (2H, d, J =
24.2 Hz, (CH3)C=CH2), 3.75 (1H, t, J = 9.2 Hz, CH-OH),
3.25 (1H, m), 3.10 (1H, m), 2.87 (1H, m), 2.63 (2H, m),
2.40 (2H, m), 2.36–2.11 (3H, m), 2.07 (2H, m), 1.92
(2H, m), 1.78 (1H, m), 1.74 (3H, s, (CH3)C=CH2), 1.61
(5H, m), 1.14 (3H, s, (C=O)-C-CH3), 1.11 (1H, m). 13C
NMR (75 MHz, CDCl3, ppm) δ: 147.4, 133.5, 127.3, 110.2,
73.9, 61.5, 46.0, 39.7, 36.9, 34.8, 34.7, 31.7, 30.6, 28.5,
25.8, 25.3, 23.8, 23.3, 23.0, 22.6, 22.3. EI-MS: 364 ([M]+).
HR-MS ([M]+) calcd. for C21H32OS2: 364.1894; found:
364.1888.
1
2923, 1693, 1438, 1407, 1376, 1301, 1103, 894, 755. H
The major diastereoisomer of the preceding alcohol
(4.5 mg, 0.012 mmol) was dissolved in dichloromethane
(0.35 mL) and pyridine (0.35 mL). 4-Nitrobenzoyl chloride
(0.023 g, 0.12 mmol) and DMAP (0.7 mg, 6.0 µmol) were
added, and the solution was stirred for 16 h at room temper-
ature and concentrated under reduced pressure, and the crude
product was purified by flash chromatography (hexane–ether
95:5) to give nitrobenzoate 20 (2.5 mg, 40%) as a yellow
solid. IR (film, cm–1) ν: 2928, 1720, 1608, 1529, 1148,
NMR (300 MHz, CDCl3, ppm) δ: 6.19 (1H, s, C=CH), 4.86
and 4.59 (2H, 2s, (CH3)C=CH2), 3.25 (1H, m), 3.05
(1H, m), 2.81 (2H, m), 2.63 (3H, m), 2.38 (3H, m), 2.12
(3H, m), 1.95 (2H, m), 1.79 (3H, s, (CH3)C=CH2), 1.62
(5H, m), 1.27 (1H, dd, J = 8.1 and 4.0 Hz), 1.17 (3H, s,
(C=O)-C-CH3). 13C NMR (75 MHz, CDCl3, ppm) δ: 208.9,
147.4, 132.2, 128.1, 111.1, 59.9, 45.0, 43.7, 40.4, 39.5, 35.4,
31.5, 30.7, 28.3, 25.8, 25.1, 24.2, 23.2, 22.5, 21.7, 18.2. EI-
MS: 362 ([M]+). HR-MS ([M]+) calcd. for C21H30OS2:
1
1409, 1348, 1321, 1272, 1117, 1104, 755, 719. H NMR
362.1738; found: 362.1743. Minor product 2b: [α]D
=
(300 MHz, CDCl3, ppm) δ: 8.32 (4H, m, H arom.), 6.46
(1H, s, C=CH), 5.35 (1H, dd, J = 7.7 and 10.9 Hz, CH-
OAc), 4.91 (2H, d, J = 24.3 Hz, (CH3)C=CH2), 3.26
(1H, m), 3.13 (1H, m), 2.91 (1H, dt, J = 13.9 and 3.1 Hz),
2.67 (2H, m), 2.45 (1H, m), 2.37 (3H, m), 2.25 (1H, m),
1.98 (2H, m), 1.87 (1H, m), 1.83 (3H, s, (CH3)C=CH2),
1.65–1.46 (7H, m), 1.26 (1H, m), 1.14 (3H, s, -CO2-C-C-
CH3). 13C NMR (75 MHz, CDCl3, ppm) δ: 164.5, 146.7,
134.1, 130.8, 126.6, 123.5, 110.8, 85.0, 78.0, 61.0, 46.9,
46.6, 39.8, 37.1, 32.0, 31.2, 30.5, 30.5, 28.3, 25.3, 25.2,
23.3, 23.2, 22.9, 22.4, 22.4. EI-MS: 513 ([M]+). HR-MS
([M]+) calcd. for C28H35NO4S2: 513.2007; found: 513.1997.
–96.25° (c 0.40, CHCl3). IR (film, cm–1) ν: 2925, 1692,
1448, 1409, 1305, 1101, 894, 730. 1H NMR (300 MHz,
CDCl3, ppm) δ: 5.91 (1H, s, C=CH), 4.85 and 4.62 (2H, 2s,
(CH3)C=CH2), 3.30 (1H, m), 3.26 (1H, m), 2.90 (3H, m),
2.76 (1H, dd, J = 16.7 and 4.9 Hz), 2.63 (3H, m), 2.46–2.18
(3H, m), 2.12 (3H, m), 1.88 (3H, m), 1.77 (3H, s,
(CH3)C=CH2), 1.66 (3H, m), 1.35 (3H, s, (C=O)-C-CH3),
1.27 (1H, m). 13C NMR (75 MHz, CDCl3, ppm) δ: 210.2,
147.5, 133.1, 128.3, 126.7, 111.0, 56.7, 44.2, 40.4, 35.9,
31.6, 30.6, 28.2, 25.8, 25.7, 24.0, 23.1, 22.4, 21.6, 17.4,
14.1. EI-MS: 362 ([M]+). HR-MS ([M]+) calcd. for
© 2003 NRC Canada

Trudeau and Deslongchamps
1011
search Council of Canada (NSERC) and Le fonds québécois
de la recherche sur la nature et les technologies (FQRNT).
We wish to thank Mr. Andreas Decken (University of New
Brunswick) for X-ray analysis, as well as Mr. Gaston Boulay
for MS analyses and Dr. Hamid Hoveyda for the preparation
of the manuscript.
Conclusion
We have studied the plausibility of an SN2′ cyclization us-
ing a silyl enol ether onto an allylic acetate by varying the
functional groups adjacent to the acetate leaving group.
Clearly, the inductive effect of the neighboring group plays a
significant role in the departure of the leaving group, as the
results with the dithiane neighboring group revealed. Several
other alternatives were pursued but without success. Unfor-
tunately, the model studies discussed herein proved that this
strategy cannot be employed to access the C7–C8 unsaturated
tricyclic structures. However, in the case of the substrates
containing a dithiane next to the allylic acetate, the synthesis
of novel highly functionalized cyclopropanes was observed
instead of the desired SN2′ cyclization. This cyclopro-
panation is due to the cyclization of the silyl enol ether with
concomitant 1,2-migration of a thioether and displacement
of the acetate.
References
1. S. Hashimoto, A. Itoh, Y. Kitawaga, H. Yamamoto, and H.
Nozaki. J. Am. Chem. Soc. 99, 4192 (1977).
2. F.G. Bordwell and B.B. Jarvis. J. Org. Chem. 33, 1182 (1968).
3. N. Toyooka, M. Okumura, H. Takahata, and H. Nemoto. Tetra-
hedron, 55, 10 673 (1999).
4. A.B. Smith III, K.J. Hale, and J.P. McCauley, Jr. Tetrahedron
Lett. 30, 5579 (1989).
5. K. Kudo, Y. Hashimoto, H. Houchigai, M. Hasegawa, and K.
Saigo. Bull. Chem. Soc. Jpn. 66, 848 (1993).
6. D. Seebach, I. Willert, A.K. Beck, and B-T. Gröbel. Helv.
Chim. Acta, 61, 2510 (1978).
7. Y. Wan, A. Kurchan, and A. Kutateladze. J. Org. Chem. 66,
1894 (2001).
Acknowledgments
A research chair from Merck Frosst is gratefully acknowl-
edged, as well as the Natural Sciences and Engineering Re-
© 2003 NRC Canada