Enantioselective Carbon-Carbon Bond Formation via SN2 Displacements of Acyclic Allylic Mesylates

Article abstract of DOI:10.1021/jo961292i

The copper-mediated S_N2′ displacement of enantiomerically pure allylic mesyloxy vinyl sulfoxides takes place with high yields and stereoselectivities. In these adducts, the newly created chiral center is adjacent to a vinyl sulfoxide functionality which should allow for subsequent chirality transfer operations. Alternatively, enantiopure alkenyl sulfones and alkenes bearing an allylic stereocenter are readily available from these adducts with high geometric control. The S_N2′ displacements of structurally related mesyloxy sulfides and sulfones with organocuprates have been examined. From a single enantiomer at the allylic alcohol position, the absolute configuration of the new chiral center may be controlled by adjusting the oxidation level on sulfur.

Full text of DOI:10.1021/jo961292i

J . Org. Chem. 1997, 62, 645-653
645
En a n tioselective Ca r bon -Ca r bon Bon d F or m a tion via SN2′
Disp la cem en ts of Acyclic Allylic Mesyla tes1
J oseph P. Marino,* Alma Viso,† and J ae-Don Lee
Department of Chemistry, The University of Michigan, Ann Arbor, Michigan 48109-1055
Roberto Ferna´ndez de la Pradilla,* Paloma Ferna´ndez, and M. Bele´n Rubio
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva, 3, 28006 Madrid, Spain
Received J uly 9, 1996X
The copper-mediated SN2′ displacement of enantiomerically pure allylic mesyloxy vinyl sulfoxides
takes place with high yields and stereoselectivities. In these adducts, the newly created chiral
center is adjacent to a vinyl sulfoxide functionality which should allow for subsequent chirality
transfer operations. Alternatively, enantiopure alkenyl sulfones and alkenes bearing an allylic
stereocenter are readily available from these adducts with high geometric control. The SN2′
displacements of structurally related mesyloxy sulfides and sulfones with organocuprates have
been examined. From a single enantiomer at the allylic alcohol position, the absolute configuration
of the new chiral center may be controlled by adjusting the oxidation level on sulfur.
Acyclic stereocontrol2 remains a challenging problem
in synthesis, especially when efficient methods for enan-
tiocontrolled carbon-carbon bond formation are required.
While enantiomerically pure sulfoxides are valuable
synthetic intermediates3 for a variety of processes, in-
cluding enantiocontrolled carbon-carbon bond formation
by conjugate addition in cyclic cases,4 their usefulness
for such alkylations in acyclic cases has not been firmly
established.4f Moreover, most sulfoxide-directed alkyla-
tion protocols utilize the valuable sulfur auxiliary just
once, and this limits the synthetic versatility of the
process.
subsequent chirality transfer operations after the crucial
alkylation step and thus significantly enhance the syn-
thetic versatility of the process. To this end, and in
connection with our interest in the use of vinyl sulfoxides
in synthesis and in organocopper chemistry,5 we consid-
ered that allylic sulfinyl alcohols A6 (Scheme 1) could lead
to the desired targets B (n ) 1), if conditions to carry
out the proposed SN2′ process7 in a highly regio- and
stereoselective fashion were developed. It should be
pointed out that systems such as B would not just allow
for subsequent sulfoxide (n ) 1)-directed chemistry but
also, if desired, the related sulfones (n ) 2) and sulfides
With this background in mind, we considered the
design of a vinyl sulfoxide system which would allow for
(5) For
a summary of the enantiospecific lactonization of vinyl
sulfoxides, see: (a) Marino, J . P. Pure Appl. Chem. 1993, 65, 667-
674. See also: (b) Ferreira, J . T. B.; Marques, J . A.; Marino, J . P.
Tetrahedron: Asymmetry 1994, 5, 641-648. (c) Marino, J . P.; Bogdan,
S.; Kimura, K. J . Am. Chem. Soc. 1992, 114, 5566-5572. For leading
organocopper references, see: (d) Marino, J . P.; Ferna´ndez de la
Pradilla, R.; Laborde, E. J . Org. Chem. 1987, 52, 4898-4913. (e)
Marino, J . P.; Tucci, F.; Comasseto, J . V. Synlett 1993, 761-763.
(6) For the early report on R-metalation of vinyl sulfoxides, see: (a)
Posner, G. H.; Tang, P. W.; Mallamo, J . P. Tetrahedron Lett. 1978,
3995-3998. (b) Okamura, H.; Mitsuhira, Y.; Miura, M.; Takei, H.
Chem. Lett. 1978, 517-520. For other related reports, see: (c) Fawcett,
J .; House, S.; J enkins, P. R.; Lawrence, N. J .; Russell, D. R. J . Chem.
Soc., Perkin Trans. 1 1993, 67-73. (d) Cheng, H.-C.; Yan, T.-H.
Tetrahedron Lett. 1990, 31, 673-676. (e) House, S.; J enkins, P. R.;
Fawcett, J .; Russell, D. R. J . Chem. Soc., Chem. Commun. 1987, 1844-
1845. (f) Holton, R. A.; Kim, H. B. Tetrahedron Lett. 1986, 27, 2191-
2194. (g) Posner, G. H.; Kogan, T. P.; Haines, S. R.; Frye, L. L.
Tetrahedron Lett. 1984, 25, 2627-2630.
(7) For reviews on SN2′ reactions, see: (a) Marshall, J . A. Chem.
Rev. 1989, 89, 1503-1511. (b) Magid, R. M. Tetrahedron 1980, 36,
1901-1930. For reviews on organocopper chemistry, see: (c) Knochel,
P.; Singer, R. D. Chem. Rev. 1993, 93, 2117-2188. (d) Wipf, P.
Synthesis 1993, 537-557. (e) Lipshutz, B. H.; Sengupta, S. Org. React.
1992, 41, 135-631. (f) Kozlowski, J . A.: Organocuprates in the
Conjugate Addition Reaction. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4,
pp 169-198. (g) Lipshutz, B. H. Synlett 1990, 119-128. (h) Lipshutz,
B. H. Synthesis 1987, 325-341. (i) Yamamoto, Y. Angew. Chem., Int.
Ed. Engl. 1986, 25, 947-959, and references cited therein. For leading
references on copper-mediated cross-coupling reactions with allylic
derivatives, see: (j) Gais, H.-J .; Mu¨ller, H.; Bund, J .; Scommoda, M.;
Brandt, J .; Raabe, G. J . Am. Chem. Soc. 1995, 117, 2453-2466. (k)
Ba¨ckvall, J .-E.; Persson, E. S. M.; Bombrun, A. J . Org. Chem. 1993,
59, 4126-4130. (l) Arai, M.; Kawasuji, T.; Nakamura, E. J . Org. Chem.
1993, 58, 5121-5129. (m) Ibuka, T.; Suzuki, K.; Habashita, H.; Otaka,
A.; Tamamura, H.; Mimura, N.; Miwa, Y.; Taga, T.; Fujii, N. J . Chem.
Soc., Chem. Commun. 1994, 2151-2152. (n) Girard, C.; Mandville, G.;
Bloch, R. Tetrahedron: Asymmetry 1993, 4, 613-616. (o) Kang, S.-K.;
Lee, D.-H.; Sim, H.-S.; Lim, J .-S. Tetrahedron Lett. 1993, 34, 91-94.
(p) Valverde, S.; Bernabe´, M.; Go´mez, A. M.; Puebla, P. J . Org. Chem.
1992, 57, 4546-4550.
† Current address, Departamento de Qu´ımica Orga´nica I, Univer-
sidad Complutense, 28040 Madrid Spain.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1997.
(1) For a preliminary report, see: Marino, J . P.; Viso, A.; Ferna´ndez
de la Pradilla, R.; Ferna´ndez, P. J . Org. Chem. 1991, 56, 1349-1351.
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York, 1989; Vol. 19, pp 227-407. (b) Evans, D. A.; Nelson, J . V.; Taber,
T. R. Ibid. Allinger, N. L., Eliel, E. L., Wilen, S. H., Eds.; Wiley: New
York, 1982; Vol. 13, pp 1-115. (c) Mukaiyama, T.; Kobayashi, S. Org.
React. 1994, 46, 1-103. (d) Nakai, T.; Mikami, K. Org. React. 1994,
46, 105-209. (d) Bartlett, P. A. Tetrahedron 1981, 36, 3-72.
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1760. (b) Rayner, C. M. Contemporary Organic Synthesis 1995, 2, 409-
440. (c) Walker, A. J . Tetrahedron: Asymmetry 1992, 3, 961-968. (d)
The Chemistry of Sulphones and Sulphoxides; Patai, S., Rappoport,
Z., Stirling, C. J . M., Eds.; Wiley: New York, 1988. (e) Solladie´, G.
Synthesis 1981, 185-196. For leading references, see: (f) Arai, Y.;
Kontani, T.; Koizumi, T. J . Chem. Soc. Perkin Trans. 1 1994, 15-23.
(g) Maezaki, N.; Soejima, M.; Takeda, M.; Sakamoto, A.; Tanaka, T.;
Iwata, C. J . Chem. Soc., Chem. Commun. 1994, 1345-1346. (h) Kita,
Y.; Shibata, N.; Kawano, N.; Tohjo, T.; Fujimori, C.; Matsumoto, K.
Tetrahedron Lett. 1995, 36, 115-118. (i) Chan, W.; Lee, A. W. M.;
J iang, L. Tetrahedron Lett. 1995, 36, 715-718. (j) Alonso, I.; Carretero,
J . C.; Garc´ıa Ruano, J . L. J . Org. Chem. 1994, 59, 1499-1508. (k)
Girodier, L. D.; Rouessac, F. P. Tetrahedron: Asymmetry 1994, 5,
1203-1206. (l) Solladie´, G.; Almario, A. Tetrahedron: Asymmetry 1994,
5, 1717-1726. (m) Hua, D. H.; Park, J .-G.; Katsuhira, T.; Bharathi,
S. N. J . Org. Chem. 1993, 58, 2144-2150. (n) Watanabe, H.; Shimizu,
H.; Mori, K. Synthesis 1994, 1249-1254.
(4) (a) Posner, G. H. Acc. Chem. Res. 1987, 20, 72-78. (b) Posner,
G. H.; Hamill, T. G. J . Org. Chem. 1988, 53, 6031-6035. (c) Holton,
R. A.; Kennedy, R. M.; Kim, H.-B.; Krafft, M. E. J . Am. Chem. Soc.
1987, 109, 1597-1600. (d) Imanishi, T.; Ohra, T.; Sugiyama, K.; Ueda,
Y.; Takemoto, Y.; Iwata, C. J . Chem. Soc., Chem. Commun. 1992, 269-
270. (e) Pan, L.-R.; Tokoroyama, T. Tetrahedron Lett. 1992, 33, 1469-
1472. (f) Posner, G. H.; Mallamo, J . P.; Miura, K. J . Am. Chem. Soc.
1981, 103, 2886-2888.
S0022-3263(96)01292-3 CCC: $14.00 © 1997 American Chemical Society

646 J . Org. Chem., Vol. 62, No. 3, 1997
Marino et al.
Sch em e 1
focused on the use of mesylates 4a and 5a , available by
standard methods (MsCl, Et3N, THF, 0 °C). Unfortu-
nately, most attempts to isolate and/or purify phenyl-
substituted mesylate 5a resulted in spontaneous loss of
methanesulfonic acid to generate 2-sulfinyl diene 7 in
variable yields and with high E selectivity.16 At the time,
we focused on avoiding formation of these dienes and
therefore, we carried out the cuprate reaction by addition
of the crude mesylate solution onto the preformed orga-
nocuprate reagent. In this fashion, when 5a was treated
with Gilman cuprate Me2CuLi‚LiI (6 equiv, THF, -78
°C to rt), a 45:55 mixture of displacement products 10a
and 11a (Scheme 3) was obtained in a disappointing 23%
yield (Table 1, entry 2).17 Interestingly, when the crude
mixture was refluxed for 30 min (entry 3), the yield of
displacement products was increased substantially. Al-
ternatively, the use of cyanocuprate MeCuCNLi under
the same conditions afforded a much better yield (89%)
and a higher selectivity (28:72, Table 1, entry 4). Fur-
thermore, a significant improvement of the diastereose-
lectivity (6:94) of the process was realized when the
cyanocuprate was generated from a Grignard reagent
(entry 5). In contrast, diastereomeric mesylate 4a re-
acted with MeCuCNLi to produce a 6:94 ratio of isomers
8a and 9a (entry 1).18
(n ) 0) should be readily available, as well as the
corresponding desulfurized enantiopure alkenes.
In this paper we report a full account of our efforts in
this field which have resulted in an efficient methodology
to prepare enantiomerically pure trisubstituted vinyl
sulfoxides, as well as the corresponding sulfide and
sulfone analogs, B. A remarkable feature of this meth-
odology is that the absolute configuration of the newly
created chiral center may be controlled by adjusting the
oxidation state of the sulfur atom.
P r ep a r a tion of Su bstr a tes. Scheme 2 shows the
straightforward preparation of the required diastereo-
meric alcohols 2 and 3, based on the acidity of the R
hydrogen of vinyl sulfoxides6 and subsequent trapping
with an aldehyde. This process took place in good yield
but with low diastereoselectivity;8 however, all isomeric
alcohols 2 and 3 were separated readily by column
chromatography.
While at this early stage of the project, access to both
diastereomeric series was in fact desirable, we also
explored the interconversion of diastereomeric alcohols
2a and 3a . Oxidation of either isomer to keto vinyl
sulfoxide 69 proceeded smoothly (MnO2, CH2Cl2, rt, 77%),
but we were unable to effect a clean stereoselective 1,2-
reduction under a variety of reaction conditions.10 In-
stead, complex mixtures of 1,4, 1,2, and complete reduc-
tion products were obtained. Nevertheless, both isomers
could be interconverted via a Mitsunobu protocol11 (Ph3P,
DEAD, PhCO2H, THF, rt; NaOMe, MeOH; 70% two
steps) in good overall yield.
The structures of alcohols 2a and 3a and of the
corresponding displacement products (8a -10a ) were
tentatively assigned by spectroscopic methods, primarily
1
by inspection of their H NMR data and on the basis of
(15) (a) Fujii. N.; Nakai, K.; Habashita, H.; Yoshizawa, H.; Ibuka,
T.; Garrido, F.; Mann, A.; Chounan, Y.; Yamamoto, Y. Tetrahedron
Lett. 1993, 34, 4227-4230. (b) Ibuka, T.; Taga, T.; Habashita, H.;
Nakai, K.; Tamamura, H.; Fujii, N.; Chounan, Y.; Nemoto, H.;
Yamamoto, Y. J . Org. Chem. 1993, 58, 1207-1214. (c) Ibuka, T.;
Yoshizawa, H.; Habashita, H.; Fujii, N.; Chounan, Y.; Tanaka, M.;
Yamamoto, Y. Tetrahedron Lett. 1992, 33, 3783-3786. (d) Ibuka, T.;
Yamamoto, Y. Synlett 1992, 769-777 and references cited therein. (e)
Burke, S. D.; Piscopio, A. D.; Kort, M. E. Tetrahedron Lett. 1991, 32,
855-856.
(16) The structure of this diene was deduced from its 1H NMR data
(CDCl3, 300 MHz) δ 1.77 (d, 3 H, J ) 5.1 Hz), 2.38 (s, 3 H), 6.06 (dq,
1 H, J ) 16.2, 5.5 Hz), 6.20 (d, 1 H, J ) 16.5 Hz), 7.26-7.60 (m, 10 H).
For other reports on enantiomerically pure 2-sulfinyl dienes, see: (a)
Paley, R. S.; Weers, H. L.; Ferna´ndez, P.; Ferna´ndez de la Pradilla,
R.; Castro, S. Tetrahedron Lett. 1995, 36, 3605-3608. (b) Bonfand, E.;
Gosselin, P.; Maignan, C. Tetrahedron: Asymmetry 1993, 4, 1667-
1676. (c) Bonfand, E.; Gosselin, P.; Maignan, C. Tetrahedron Lett. 1992,
33, 2347-2348. (d) Aversa, M. C.; Bonaccorsi, P.; Gianneto, P.; J afari,
S. M. A.; J ones, D. N. Tetrahedron: Asymmetry 1992, 3, 701-704. For
reports on the highly stereoselective Diels-Alder reactivity of these
dienes, see: (e) Gosselin, P.; Bonfand, P.; Hayes, P.; Retoux, R.;
Maignan, C. Tetrahedron: Asymmetry 1994, 5, 781-784. (f) Aversa,
M. C.; Bonaccorsi, P.; Gianneto, P.; J ones, D. N. Ibid. 1994, 5, 805-
808.
Cu p r a te SN2′ Disp la cem en ts on Su lfoxid es. At the
initial stage of this investigation we focused on phenyl-
substituted substrates 2a , 3a , and we attempted to carry
out the allylic displacement on the free alcohols, by the
use of organocopper reagents in the presence of BF3‚
OEt2 or TMSCl/Et3N13 which resulted in recovery of
12
starting material or formation of silyl ethers, respectively.
We then turned our attention into the corresponding
acetates14 (Ac2O, pyr) with mixed results, and, in some
instances we obtained low yields of the desired displace-
ment products, along with some deacetylation to the
parent alcohols.
(17) Under these conditions, the major product found was assigned
as PhCHdCdCHEt. For
a discussion of these allene producing
In view of recent reports on efficient chirality transfer
experiments, see: Ferna´ndez de la Pradilla, R.; Rubio, M. B.; Marino,
J . P.; Viso, A. Tetrahedron Lett. 1992, 33, 4985-4988.
by cuprate SN2′ displacements on allylic mesylates15 we
(18) The behavior for the enantiomeric series of phenyl-substituted
sulfinyl alcohols, ent-2a and ent-3a (prepared in a standard fashion
from commercially available (+)-menthyl (RS)-p-toluenesulfinate) was
examined, giving rise to the expected displacement products ent-9a
and ent-11a with good yields and stereoselectivities. These products
were fully characterized by spectroscopic techniques, and their data
was found to be identical to their corresponding enantiomers with the
exception of the sign of their optical rotation.
(8) Low stereoselectivities have been reported for these processes.
See: (a) Posner, G. H.; Mallamo, P.; Miura, K.; Hulce, M. Pure Appl.
Chem. 1981, 54, 2307-2314. For one example in which
a high
diastereoselectivity was found, see: (b) Solladie´, G.; Moine, G. J . Am.
Chem. Soc. 1984, 106, 6097-6098.
(9) Trapping of the vinyl anion with propionyl chloride or ethyl
propionate, more direct routes to 6, failed in our hands.
(10) These include: DIBALH; DIBALH/ZnCl2; LAH; NaBH4/CeCl3;
LAH/CeCl3; 9-BBN.
(11) (a) Grynkiewicz, G.; Burzynska, H. Tetrahedron 1976, 32,
2109-2111. (b) Hughes, D. L., Org. React. 1992, 42, 335-669.
(12) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Maruyama, K. J .
Am. Chem. Soc. 1980, 102, 2318-2325.
(13) Amri, H.; Rambaud, M.; Villieras, J . Tetrahedron 1990, 46,
3535-3546.
(14) For pertinent references on coupling of cuprates with allylic
carboxylates, see: Underiner, T. L.; Paisley, S. D.; Schmitter, J .;
Lesheski, L.; Goering, H. L. J . Org. Chem. 1989, 54, 2369-2374 and
references cited therein.

Carbon-Carbon Bond Formation via SN2′ Displacements
Sch em e 2
J . Org. Chem., Vol. 62, No. 3, 1997 647
Sch em e 3
In a parallel fashion, the behavior of diastereomer 5b was
explored; interestingly, MeCuCNLi produced the E iso-
mer 10b as major product (entry 13). An additional
improvement was found when Me2CuLi‚LiI was em-
ployed. In view of the results found for phenyl-substi-
tuted mesylate 5a and Grignard-derived cuprates, we
tested MeCuCNMgBr and we found a remarkable rever-
sal of selectivity albeit not quite synthetically useful
(entry 15). Furthermore, Me2CuMgBr afforded exclu-
sively Z isomer 11b (entry 16). Since the reaction
proceeded in modest yield, we cannot rule out selective
destruction of the E isomer; nevertheless, entries 15 and
16 suggest that complete control of the selectivity of the
process may also be possible at least in some cases, after
the appropriate optimization.
Hydrocinnamaldehyde-derived substrates 4d and 5d
were studied next with the intent of probing any effects
of a tethered phenyl ring on the stereoselectivity. The
results largely paralleled those found for 4b and 5b. Thus
4d displayed good selectivity upon reaction with MeCuCN-
Li, even at 0 °C (entries 18 and 19) and 5d displayed
good E selectivity with Me2CuLi‚LiI (entry 20). Methyl-
substituted mesylate 5c, on the other hand, reacted in
high yield but low selectivity with n-BuCuCNLi (entry
21) and with very high selectivity but modest yield with
n-Bu2CuMgCl (compare with entries 13 and 16). Alter-
natively, Grignard-derived phenyl homo and cyanocu-
prates gave good yields and high diastereoselectivities
(entries 23 and 24). On the other hand, the reactions
between diastereomeric mesylate 4c and n-BuCuCNLi
and PhCuCNLi proceeded in very good yields and with
good stereocontrol (entries 25 and 26).
an anti attack of the nucleophile.7,15 The stereochemistry
of the double bond was deduced from the chemical shift
of the vinylic proton (0.40-0.55 ppm more deshielded in
E isomers 8a and 10a ). Additionally, the newly intro-
duced methyl group appeared shielded in isomers 8a
(0.35 ppm) and 11a (0.52 ppm) relative to 10a and 9a ,
respectively (a similar unusual shielding had been ob-
served for the CH3SO2 methyl of mesylate 4a ). All of
these spectral characteristics were consistent with a
predominant conformation in solution which would place
the aforementioned methyl groups in the shielding region
of the anisotropic tolyl group.
To extend the scope of the methodology, the introduc-
tion of a bulky tert-butyl group was addressed and good
selectivities were encountered (entries 6 and 7 of Table
1) with lithium and Grignard-derived cuprates. The
reactivity of n-butyl-substituted vinyl sulfoxides 4b and
5b was then studied, and the results are shown in Table
1 (entries 8-16). In the case of isomer 4b, a significant
increase in selectivity was achieved with MeCuCNLi
relative to Gilman’s cuprate. With MeCuCNLi a further
improvement was observed when the reaction was car-
ried out in a DME/THF (9:1) solvent mixture. Entry 10
shows that the process is compatible with the use of
Lewis acids while a small decrease in selectivity and in
yield was observed. On the other hand, the use of Me2-
CuMgBr resulted in a significant decrease in selectivity.
Cu p r a t e Disp la cem en t s on Vin yl Su lfid es a n d
Su lfon es. While the diastereomeric nature of our me-
sylates and displacement adducts indicated that both
chiral centers (allylic alcohol and sulfur) participated in
the stereocontrol of the process, at least in some cases
(see below), we considered that varying the oxidation
state on sulfur to sulfone and sulfide would not just
extend the scope of the methodology but also shed some
light on the stereochemical course of the process.
Enantiomerically pure sulfonyl- and sulfenyl-substi-
tuted allylic alcohols 12 and 13 were prepared in excel-
lent yields by oxidation or deoxygenation, respectively,
of the corresponding sulfoxides (Scheme 4). We decided
to focus our efforts on the conjugate addition of methyl

648 J . Org. Chem., Vol. 62, No. 3, 1997
Marino et al.
yield (%)b
Ta ble 1. Rea ction of Or ga n ocop p er Rea gen ts w ith Allylic Su lfin yl Mesyla tes
product ratio
entry
substrate
R2Cua (conditions)
8
9
10
11
1c
2c
4a
5a
5a
5a
5a
4a
5a
4b
4b
4b
4b
4b
5b
5b
5b
5b
4d
4d
4d
5d
5c
5c
5c
5c
4c
4c
MeCuCNLi
Me2CuLi
Me2CuLi (-78 °C-∆)
MeCuCNLi
MeCuCNMgBr
t-BuCuCNLi
t-BuCuCNMgCl
Me2CuLi
6 (8a )
94 (9a )
81
23
80
89
80
69
71
81
80
58
52
86
86
80
80
50
82
77
77
85
93
43
80
70
74
85
45 (10a )
45 (10a )
28 (10a )
6 (10a )
55 (11a )
55 (11a )
72 (11a )
94 (11a )
3c
4c
5c
6c
9 (8e)
91 (9e)
7c
6 (10e)
94 (11e)
8
9
25 (8b)
12 (8b)
15 (8b)
36 (8b)
9 (8b)
75 (9b)
88 (9b)
85 (9b)
64 (9b)
91 (9b)
MeCuCNLi
10
11
12d
13
14
15
16
17
18
19
20
21
22
23
24
25
26d
MeCuCNLi‚BF3‚OEt2
Me2CuMgBr
MeCuCNLi
MeCuCNLi
Me2CuLi
MeCuCNMgBr
Me2CuMgBr
Me2CuLi
MeCuCNLi (0 °C)
MeCuCNLi (-78 °C)
Me2CuLi
n-BuCuCNLi
n-Bu2CuMgCl
PhCuCNMgBr
Ph2CuMgBr
n-BuCuCNLi
PhCuCNLi
80 (10b)
90 (10b)
37 (10b)
0 (10b)
20 (11b)
10 (11b)
63 (11b)
100 (11b)
28 (8d )
16 (8d )
8 (8d )
72 (9d )
84 (9d )
92 (9d )
85 (10d )
15 (11d )
60 (8b)
0 (8b)
9 (8a )
6 (8a )
40 (9b)
100 (9b)
91 (9a )
94 (9a )
15 (10b)
0 (10a )
85 (11b)
100 (11a )
a
Cuprates R2Cu were prepared from the appropriate organolithium or Grignard reagent and CuI or CuCN. All experiments were
b
carried out from -78 °C to rt unless otherwise stated. Yields of pure products calculated from alcohols 2 and 3. Product ratios were
measured by integration of well separated absorptions of the 1H NMR spectra of crude reaction mixtures. c The crude mesylate solution
d
was added to the organocuprate solution (6 equiv) at -78 °C. The reaction was carried out in a DME/THF (9:1) solvent mixture; these
conditions produced a slight increase of the selectivity of the reaction.
Sch em e 4
Sch em e 5
stereoselectivity toward the Z isomers 17, and ent-17
(entries 6 and 7), as was found for the sulfoxides.
nucleophiles and the experiments performed are gathered
in Scheme 5 and Table 2. Vinyl sulfone 12 was first
examined (entries 1-4), and the best results were
obtained with “higher order” cyanocuprates derived from
a Grignard reagent (entry 4), in sharp contrast with the
lithium analogs (entry 1). The very high E selectivity of
this process, opposite to the related sulfoxides, is note-
worthy. A similar behavior was observed for ent-12
within experimental error (Table 2, entry 5). On the
other hand, vinyl sulfides 13 and ent-13 displayed high
While the stereochemistry of the double bond of these
vinyl sulfones and sulfides was readily established by 1H
NMR, the configuration of the new chiral center required
a chemical correlation for vinyl sulfide 17 to the corre-
sponding sulfone 15 which possessed an identical optical
rotation to the sample prepared by oxidation of sulfoxide
11a of known absolute configuration1 (Scheme 6). Fur-
thermore, the structures of the minor SN2′ displacement

Carbon-Carbon Bond Formation via SN2′ Displacements
J . Org. Chem., Vol. 62, No. 3, 1997 649
Ta ble 2. Rea ction of Or ga n ocop p er Rea gen ts w ith
Allylic Su lfon yl a n d Su lfen yl Mesyla tes
Sch em e 8
yield
entrya substrate
“MeCu”
products
ratio (%)b
1c
2
3
12
12
12
Me2CuCNLi2
MeCuCNLi
MeCuCNMgBr
-
14:15
14:15
-
-
50:50 72
83:17 74
4
5
6
7
12
ent-12
13
Me2CuCN(MgBr)2 14:15
Me2CuCN(MgBr)2 ent-14:ent-15 93:7
91:9
76
81
MeCuCNMgBr
MeCuCNMgBr
16:17
6:94 58
ent-13
ent-16:ent-17 6:94 61
a
Reactions carried out in THF (-78 °C to rt) by addition of the
b
crude mesylate solution to the organocuprate solution. Yields of
pure products for two steps (mesylation and cuprate displacement).
c Only product observed was PhCHdCdCHEt; the yield was not
determined.
Sch em e 9
Sch em e 6
Sch em e 7
ucts; that is to say, in no case were products 10 and 11
detected from mesylates 4.21,22 Diastereomers 4a -d
generally afforded products consistent with oxidative
addition anti to the mesylate and away from the tolyl
group on conformation C. Diastereomers 5a -d display
a somewhat more complex behavior. Indeed conforma-
tion D represents a very delicately balanced case, highly
dependent on the reaction conditions and on the steric
requirements of the substrate. Thus, when the steric
interaction between R and R1 is very strong (R ) Ph, R1
) Et), adduct 11 becomes the main product of the
reaction (entries 5 and 7, Table 1), indicating that E is
the reactive conformation in this substrate. However,
when Grignard-derived cuprates are employed the best
selectivities toward 11 were achieved. This trend may
also be reinforced by participation of chelated forms
involving the sulfoxide oxygen and the mesylate group
(entries 14-16) and may be rationalized in terms of a
reactive conformation similar to E′.
The behavior of sulfide 13 with MeCuCNMgBr closely
parallels the corresponding sulfoxides, and a highly anti
selective displacement on a conformation related to C is
observed to provide the corresponding displacement
product 17 (Scheme 5). The results found for sulfones
12 may be interpreted in terms of an anti addition to
reactive conformer F (Scheme 9) to provide adduct 14 of
E geometry, although a severe steric interaction between
Et and Ph is present in that conformer. Alternatively
14 may arise from a syn nucleophilic attack on reactive
sulfoxides 8a and 10a (Scheme 3) were secured by
oxidation of 10a with MMPP to produce sulfone 14.
Syn th esis of Alk en es Con ta in in g a n Allylic Asym -
m etr ic Ca r bon . To begin exploring the synthetic use-
fulness of our SN2′ adducts, we decided to focus on the
cleavage of the carbon-sulfur bond to produce enan-
tiopure alkenes.19 We selected adducts 10d and 11d
(Scheme 7) to diminish losses of material due to the
predicted volatility of other alkenes derived from different
substrates. In this regard, we found that Okamura’s
method20 gave rise to alkenes 18 and 19 in good yield
and with complete preservation of the stereochemistry
of the double bond.
Resu lts a n d Discu ssion
The results obtained for the cuprate displacement of
allylic sulfinyl mesylates may be rationalized in terms
of an anti SN2′ process taking place on reactive conforma-
tions C and D for sulfoxides 4 and 5 (Scheme 8). The
clean anti stereochemistry of these displacements is
firmly established from the absence of “crossover” prod-
(19) Enantiopure alkenes are frequently found in nature. The
structure of some pheromones is an example, see: The Synthesis of
Insect Pheromones. In The Total Synthesis of Natural Products; Mori,
K., ApSimon, J ., Eds.; J ohn Wiley & Sons: New York, 1992; Vol. 9.
(20) Park, G.; Okamura, W. H. Synth. Commun. 1991, 21, 1047-
1054.
(21) For leading references on syn selective SN2′ displacements
involving organocopper reagents, see ref 15b and references cited
therein. See also ref 5d.
(22) Mesylates 5c and 4c produce “crossover” products only in a
formal sense due to the exchange of the ligand on copper and the R
group on the mesylate.

650 J . Org. Chem., Vol. 62, No. 3, 1997
Marino et al.
placements were carried out in a 0.5-2 mmol scale. Reagents
and solvents were handled by using standard syringe tech-
niques. Diethyl ether, tetrahydrofuran, and 1,2-dimethoxy-
ethane were distilled from sodium and benzophenone; N,N-
diisopropylamine, triethylamine, and pyridine from barium
oxide or calcium hydride. Commercial methyllithium (low
halide solution in ether), n-butyllithium (solution in hexane),
phenyllithium (solution in cyclohexane:ether, 70:30), and tert-
butyllithium (in pentane) were purchased from Aldrich and
titrated prior to use.27 Methylmagnesium bromide (in ether),
phenylmagnesium bromide (in ether), and tert-butylmagne-
sium chloride (in ether) were purchased from Aldrich. Copper
cyanide, copper iodide, propionaldehyde, and hydrocinnamal-
dehyde were purchased from Aldrich. Copper cyanide was
heated at 90-100 °C in vacuo for 2 h and stored in a desiccator.
Copper iodide was purified from aqueous KI28 and dried or
washed with refluxing THF in a Soxhlet apparatus and stored
in a desiccator. Flash chromatography was performed using
Baker 40-µm and Merck 230-400-mesh silica gel. Analytical
TLC was carried out on 250-µm Analtech or Merck (Kiesegel
60F-254) silica gel plates with detection by UV light, iodine,
acidic vanillin solution, or phosphomolybdic acid solution in
ethanol. Melting points are uncorrected. 1H and 13C NMR
spectra were recorded at 300 or 360 MHz (1H) using CDCl3 as
solvent. The following abbreviations were used to describe
peak patterns when appropriate: br ) broad, s ) singlet, d )
doublet, t ) triplet, q ) quartet, m ) multiplet. Optical
rotations were measured at 20 °C using a sodium lamp and
in CHCl3 solution.
conformer G followed by rotation of the intermediate
R-sulfonyl carbanion to deliver the thermodynamically
more stable E configuration about the newly formed
carbon-carbon double bond. It should also be noted that
the greater carbanion-stabilizing power of the sulfone
group could be rendering the addition process less
concerted than for the sulfide or sulfoxide systems. The
lack of selectivity found for MeCuCNLi (Table 2, entry
2) is in sharp contrast with previous results in the
literature for simpler sulfonyl acetates23 for which com-
plete E selectivity was found upon reaction with lithium
cyanocuprates; this suggests that while syn SN2′ pro-
cesses are well documented for cyclic vinyl sulfones24 our
displacement is likely taking place with predominantly
anti stereochemistry in a single SN2′ step on chelated
conformer F ′, especially when Grignard derived cuprates
are employed.
Overall the stereochemical outcome of these processes
is primarily controlled by the configuration of the allylic
mesylate with sulfides and sulfoxides displaying very
similar results. The related sulfones allow for a reversal
of stereochemistry at the newly created center from a
starting material of the same absolute configuration at
the allylic alcohol.
Con clu sion s
Gen er a l P r oced u r e for th e Con d en sa tion betw een
Vin yl Su lfoxid es a n d Ald eh yd es. To a cold (-78 °C) 0.1 M
THF solution of 1.5 equiv of LDA, previously formed at 0 °C,
was added 1 equiv of 1a -d in THF (5 mL/mmol). After
stirring for 15 min, 1.5 equiv of the aldehyde was added
dropwise. The mixture was quenched after 15 min of stirring
with a saturated NH4Cl solution. The aqueous layer was
washed with ethyl acetate (4 × 10 mL/mmol of starting
material). Then, the organic layer was washed with a satu-
rated NaCl solution, dried over anhydrous MgSO4, and filtered.
Concentration under reduced pressure gave a crude product,
which was purified by column chromatography on silica gel,
using the appropriate mixture of CH2Cl2 and ethyl acetate as
eluent.
(E)-1-P h en yl-2(Ss)-(p-tolylsu lfin yl)pen t-1-en -3(R)-ol, 2a,
a n d (E)-1-P h en yl-2(Ss)-(p-tolylsu lfin yl)p en t-1-en -3(S)-ol,
3a . 2a and 3a were obtained as a 40:60 mixture and were
separated by chromatography on silica gel (80% combined
yield). Data of 2a : white solid. Mp: 143-144 °C (CH2Cl2:
hexane). Rf ) 0.33 (10% EtOAc-CH2Cl2). [R] ) +91.9 (1.02).
1H NMR: δ 0.85 (t, 3 H, J ) 7.4 Hz), 1.58-1.69 (m, 1 H), 1.70-
1.81 (m, 1 H), 2.39 (s, 3 H), 4.72 (dd, 1 H, J ) 8.5, 5.5 Hz),
7.25-7.49 (m, 8 H), 7.61-7.64 (d, 2 H, J ) 8.2 Hz). 13C NMR:
δ 10.3, 21.3, 29.2, 71.2, 125.8, 128,7, 128.8, 129.5, 130.1, 133.3,
134.4, 141.8, 147.8. Data of 3a : white solid. Mp: 116-117
°C (CH2Cl2:hexane). Rf ) 0.18 (10% EtOAc-CH2Cl2). [R] )
-16.0 (1.23). 1H NMR: δ 0.78 (t, 3 H, J ) 7.4 Hz), 1.36 (m, 2
H), 2.39 (s, 3 H), 3.40 (br s, 1 H), 4.68 (t, 1 H, J ) 6.8 Hz),
7.24-7.44 (m, 8 H), 7.50-7.63 (m, 2 H). 13C NMR: δ 10.5,
21.4, 29.0, 71.5, 126.2, 128.6, 129.6, 130.1, 132.1, 134.4, 140.9,
141.9, 148.8.
A new methodology to effect the regio- and stereocon-
trolled SN2′ displacement of allylic mesyloxy vinyl sulf-
oxides and their oxidation/reduction analogs has been
developed. The scope of this methodology has been
defined, and in this manner, the newly created chiral
center is adjacent to the synthetically useful functionality
of a vinyl sulfoxide which should allow for straightfor-
ward subsequent asymmetric transformations. Addition-
ally, removal of the sulfur auxiliary to generate enan-
tiopure alkenes or oxidation to the corresponding sulfones25
are readily accomplished. The possibility of controlling
the absolute configuration of the displacement products
by adjusting the oxidation level on sulfur is remarkable.
Additional extensions of this methodology as well as
further applications to the synthesis of natural products
are being pursued in our laboratories.26
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were carried out under a
positive pressure of dry nitrogen or argon, using freshly
distilled solvents under anhydrous conditions. Cuprate dis-
(23) Auvray, P.; Knochel, P.; Normant, J . F. Tetrahedron 1988, 44,
6095-6106.
(24) For some syn SN2′ processes on cyclic vinyl sulfones, see: (a)
Arjona, O.; de Dios, A.; Ferna´ndez de la Pradilla, R.; Plumet, J .; Viso,
A. J . Org. Chem. 1994, 59, 3906-3916. (b) Braish, T.; Saddler, J . C.;
Fuchs, P. L. J . Org. Chem. 1988, 53, 3647-3658. (c) Saddler, J . C.;
Fuchs, P. L. J . Am. Chem. Soc. 1981, 103, 2112-2114.
(25) Vinyl sulfones are versatile synthetic intermediates. For re-
views, see: (a) Simpkins, N. S. Sulphones in Organic Synthesis;
Tetrahedron Organic Chemistry Series, Vol. 10; Baldwin, J . E.,
Magnus, P. D., Eds.; Pergamon Press: Oxford, 1993. (b) Cossu, S.; De
Lucchi, O.; Fabbri, D. Org. Prep. Proced. Int. 1991, 23, 571-592. (c)
Simpkins, N. S. Tetrahedron 1990, 46, 6951-6984. (d) See ref 3b. (e)
De Lucchi, O.; Pasquato, L. Tetrahedron 1988, 44, 6755-6794. (f)
Fuchs, P. L.; Braish, T. F. Chem. Rev. 1986, 86, 903-917. For leading
references, see: (g) Isobe, M.; J iang, Y. Tetrahedron Lett. 1995, 36,
567-570. (h) Enders, D.; J andeleit, B.; Raabe, G. Angew. Chem., Int.
Ed. Engl. 1994, 33, 1949-1951. (i) Carretero, J . C.; Diaz, N.; Rojo, J .;
Tetrahedron Lett. 1994, 35, 6917-6920. (j) Padwa, A.; Filipkowski, M.
A.; Meske, M.; Murphree, S. S.; Watterson, S. H.; Ni, Z. J . Org. Chem.
1994, 59, 588-596. (k) Li, C.; Fuchs, P. L. Synlett 1994, 629-630.
(26) For an application to the formal synthesis of Brassinolide, see:
Marino, J . P.; de Dios, A.; Anna, L. J .; Ferna´ndez de la Pradilla, R. J .
Org. Chem. 1996, 61, 109-117.
(E)-4(Ss)-(p-Tolylsu lfin yl)n on -4-en -3(R)-ol, 2b, a n d (E)-
4(Ss)-(p-Tolylsu lfin yl)n on -4-en -3(S)-ol, 3b. 2b and 3b were
obtained as a 44:56 mixture and were separated by chroma-
tography on silica gel (85% combined yield). Data of 2b:
transparent oil. Rf ) 0.28 (10% EtOAc-CH2Cl2). [R] ) +38.4
(3.62). 1H NMR: δ 0.84 (t, 3 H, J ) 7.3 Hz), 0.96 (t, 3 H, J )
7.2 Hz), 1.35-1.54 (m, 5 H), 1.63-1.70 (m, 1 H), 2.30-2.39
(m, 2 H), 2.42 (s, 3 H), 2.55-2.65 (br s, 1 H), 4.51 (dd, 1 H, J
) 8.3, 5.9 Hz), 6.50 (t, 1 H, J ) 7.6 Hz), 7.31 (d, 2 H, J ) 8.2
Hz), 7.55 (d, 2 H, J ) 8.2 Hz). 13C NMR: δ 10.3, 13.8, 21.3,
22.4, 28.2, 30.0, 31.1, 71.5, 125.0, 129.8, 138.2, 140.9, 141.2,
145.1. Data of 3b: transparent oil. Rf ) 0.16 (10% EtOAc-
(27) Watson, S. C.; Easthman, J . E. J . Organomet. Chem. 1967, 9,
165-168.
(28) Kauffman, G. B.; Teter, L. A. Inorg. Synth. 1963, 7, 10.

Carbon-Carbon Bond Formation via SN2′ Displacements
J . Org. Chem., Vol. 62, No. 3, 1997 651
CH2Cl2). [R] ) -5.5 (1.84). 1H NMR: δ 0.79 (t, 3 H, J ) 7.3
Hz), 0.92 (t, 3 H, J ) 6.8 Hz), 1.18-1.60 (m, 6 H), 2.23-2.44
(m, 2 H), 2.40 (s, 3 H), 2.70-2.71 (m, 1 H), 4.37 (ddd, 1 H, J
) 8.9, 4.9, 4.3 Hz), 6.31 (t, 1 H, J ) 7.6 Hz), 7.28 (d, 2 H, J )
7.4 Hz), 7.51 (d, 2 H, J ) 7.4 Hz). 13C NMR: δ 10.5, 13.8,
21.4, 22.8, 30.3, 31.2, 70.2, 125.3, 129.8, 137.4, 140.3, 141.4,
146.4.
transformed into sulfone 14 which was purified by chroma-
tography on silica gel using 10% EtOAc-hexane as eluent
(82% yield). This compound was found to be identical to
sulfone 14 obtained from the addition of Me2CuCN(MgBr)2 to
sulfone 12 as major product and whose structure was con-
firmed by X-ray analysis.
Syn th esis of (E)-1-P h en yl-2-(p-tolylsu lfen yl)p en t-1-en -
3(S)-ol, 13. A round-bottomed flask was charged with ether
(10 mL) and Zn dust (295 mg, 4.53 mmol). The flask was
immersed in an ice bath, and titanium(IV) chloride (0.25 mL,
2.26 mmol) was added with stirring at 0 °C. After 2 min the
solution of sulfoxide ent-2a (340 mg, 1.13 mmol) in dichlo-
romethane (10 mL) was slowly added. After 10 min, water
(20 mL) was added to the mixture. The organic layer was
separated and the aqueous layer was extracted with dichlo-
romethane (2 × 10 mL). The combined organic layers were
dried over MgSO4 and evaporated to give a crude product
which was purified by column chromatography on silica gel
(15% EtOAc-hexane) to afford 13 (90%). ent-13 was prepared
from ent-3a by the same procedure (92%). Data of 13: [R] )
+90.5 (1.35). 1H NMR: δ 0.93 (t, 3 H, J ) 7.4 Hz), 1.79 (m, 2
H), 2.04 (d, 1 H, J ) 7.4 Hz), 2.33 (s, 3 H), 4.72 (dd, 1 H, J )
13.8, 7.4 Hz), 6.43 (s, 1 H), 7.30-7.44 (m, 9 H). 13C NMR: δ
10.1, 21.0, 29.7, 72.0, 127.1, 128.3, 128.5, 130.1, 130.7, 132.1,
133.0, 136.6, 137.9, 143.2. Data of ent-13 was found to be
identical to 13 except for the sign of the optical rotation [R] )
-91.1 (2.17).
(E)-1-P h en yl-4(Ss)-(p-tolylsu lfin yl)n on -4-en -3(R)-ol, 2d ,
a n d (E)-1-p h en yl-4(Ss)-(p-tolylsu lfin yl)n on -4-en -3(S)-ol,
3d . 2d and 3d were obtained as a 50:50 mixture and were
separated by chromatography on silica gel (86% combined
yield). Data of 2d : white solid. Mp: 48-50 °C. Rf ) 0.36
(10% EtOAc-CH2Cl2). [R] ) +46.8 (1.12). 1H NMR: δ 0.90
(t, 3 H, J ) 7.3 Hz), 1.30-1.47 (m, 4 H), 1.60-1.70 (m, 1 H),
1.88-1.94 (m, 1 H), 2.19-2.25 (m, 2 H), 2.40 (s, 3 H), 2.40-
2.48 (m, 1 H), 2.60-2.73 (m, 2 H), 4.56 (dt, 1 H, J ) 9.0, 5.0
Hz), 6.45 (t, 1 H, J ) 7.6 Hz), 7.01 (d, 2 H, J ) 8.1 Hz), 7.13-
7.29 (m, 5 H), 7.51 (d, 2 H, J ) 8.2 Hz). 13C NMR: δ 13.7,
21.3, 22.3, 28.1, 31.0, 31.9, 38.3, 69.5, 125.2, 125.8, 128.3, 128.4,
129.9, 138.1, 140.8, 141.2, 141.3, 145.2. Data of 3d : white
solid. Mp: 112-114 °C. Rf ) 0.17 (10% EtOAc-CH2Cl2). [R]
) +74.1 (0.64). 1H NMR: δ 0.89 (t, 3 H, J ) 7.2 Hz), 1.20 (m,
1 H), 1.25-1.45 (m, 4 H), 1.87 (m, 1 H), 2.18 (m, 1 H), 2.30
(m, 1 H), 2.41 (s, 3 H), 2.45 (m, 1 H), 2.66 (m, 1 H), 3.27 (d, 1
H, J ) 4.3 Hz), 4.46 (ddd, 1 H, J ) 9.2, 5.4, 4.2 Hz), 6.30 (t, 1
H, J ) 7.6 Hz), 6.98 (d, 2 H, J ) 8.3 Hz), 7.13-7.30 (m, 5 H),
7.45 (d, 2 H, J ) 8.2 Hz). 13C NMR: δ 13.7, 21.3, 22.3, 28.4,
31.1, 32.2, 38.9, 67.5, 125.1, 125.8, 128.2, 128.4, 129.8, 138.1,
140.2, 141.2, 141.3, 146.9.
Gen er a l P r oced u r e for Oxid a tion of Su lfid es a n d
Su lfoxid es to Su lfon es. Meth od A. To a solution of 1 equiv
of sulfoxide or sulfide and NaHCO3 (2 g/mmol) in CH2Cl2 (10
mL/mmol) at 0 °C was added a solution of m-CPBA (50-60%;
1.3 or 2.6 equiv) in CH2Cl2 (2 mL). The reaction mixture was
stirred at this temperature until complete conversion was
observed by TLC and quenched with H2O (10 mL/mmol). The
organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 10 mL/mmol). The combined
organic extracts were dried over MgSO4 and evaporated to give
a crude oil which was purified by column chromatography on
silica gel to afford the corresponding sulfone.
Meth od B. To a solution of the corresponding sulfoxide (1
equiv) in MeOH (5 mL/mmol) was added MMPP (1.5 equiv).
The mixture was stirred at room temperature until complete
conversion was observed by TLC. The mixture was diluted
with CH2Cl2 and was extracted with a 5% solution of NaHCO3
and washed with brine. The organic extract was dried over
MgSO4, and the solvent was removed under reduced pressure
to yield the crude product that was purified by chromatography
on silica gel.
Syn th esis of (E)-1-P h en yl-2-(p-tolylsu lfon yl)p en t-1-en -
3(S)-ol, 12. Following the above procedure (method A), 12
was obtained from 3a (350 mg, 1.17 mmol) and was purified
by chromatography on silica gel (CH2Cl2) (86% yield). ent-12
was prepared from 2a by the same procedure (92% yield). Data
of 12. Mp: 110-111 °C. [R] ) -49.6 (1.21). Rf ) 0.20 (CH2-
Cl2). 1H NMR: δ 0.75 (t, 3 H, J ) 7.4 Hz), 1.54-1.89 (m, 2
H), 2.43 (s, 3 H), 2.87 (d, 1 H, J ) 8.9 Hz), 4.65 (m, 1 H), 7.26-
7.93 (m, 10 H). 13C NMR: δ 10.3, 21.4, 28.7, 70.4, 127.8, 128.5,
129.5, 129.6, 129.7, 133.0, 138.2, 141.0, 144.1. Data of ent-12
was found to be identical to that of 12 except for the sign of
the optical rotation [R] ) +49.9 (1.37).
Gen er a l P r oced u r e for Mesyla tion of Alcoh ols 2 a n d
3. To a cold (0 °C) solution of the alcohol in THF (0.1 M) were
added Et3N (3 equiv) and MsCl (3 equiv), and the mixture was
stirred for 1 h after which time the reaction was quenched
with a saturated NaHCO3 solution and diluted with ether, and
the layers were separated. The organic layer was washed with
a saturated NH4Cl solution and brine and dried over MgSO4.
Filtration and concentration under reduced pressure gave a
crude product which was filtered through a short column of
deactivated silica gel (washed with 5% NaHCO3 in MeOH),
using 50% EtOAc-hexane as eluent. Removal of the solvent
afforded the mesylate which was used for the cuprate displace-
ment without further purification. In the case of alcohols 2a
and 3a , the crude mesylate solution in THF was filtered and
immediately added dropwise to the cuprate reagent to avoid
formation of diene 7. The same procedure was employed for
additions to sulfones 12 and sulfides 13. Formation of all the
1
mesylates 4b-d and 5b-d was checked by H NMR.
Mesyla te of (E)-4(Ss)-(p-Tolylsu lfin yl)n on -4-en -3(R)-ol,
2b, 4b. 1H NMR: δ 0.94 (t, 3 H, J ) 7.2 Hz), 0.95 (t, 3 H, J
) 7.4 Hz), 1.35-1.54 (m, 5 H), 1.73-1.76 (m, 1 H), 1.96-2.02
(m, 1 H), 2.31 (s, 3 H), 2.38-2.45 (m, 1 H), 2.40 (s, 3 H), 5.22
(dd, 1 H, J ) 8.5, 6.8 Hz), 6.72 (t, 1 H, J ) 7.7 Hz), 7.31 (d, 2
H, J ) 8.2 Hz), 7.57 (d, 2 H, J ) 8.2 Hz).
Mesyla te of (E)-4(Ss)-(p-Tolylsu lfin yl)n on -4-en -3(S)-ol,
3b, 5b. 1H NMR: δ 0.70 (t, 3 H, J ) 7.1 Hz), 0.88 (m, 2 H),
0.95 (t, 3 H, J ) 7.2 Hz), 1.40-1.43 (m, 4 H), 2.40 (m, 2 H),
2.41 (s, 3 H), 3.01 (s, 3 H), 5.06 (dd, 1 H, J ) 5.7 Hz), 6.65 (t,
1 H, J ) 7.7 Hz), 7.32 (d, 2 H, J ) 8.1 Hz), 7.48 (d, 2 H, J )
8.2 Hz).
Mesyla te of (E)-1-P h en yl-4(Ss)-(p-tolylsu lfin yl)n on -4-
en -3(R)-ol, 2d , 4d . 1H NMR: δ 0.91 (t, 3 H, J ) 7.2 Hz), 1.30-
1.50 (m, 5 H), 1.84 (m, 1 H), 2.23-2.37 (m, 2 H), 2.40 (s, 6 H),
2.59 (m, 1 H), 2.71 (m, 1 H), 5.25 (dd, 1 H, J ) 9.1, 4.8 Hz),
6.70 (t, 1 H, J ) 7.8 Hz), 7.10 (m, 2 H), 7.17 (m, 5 H), 7.53 (d,
2 H, J ) 8.2 Hz).
Mesyla te of (E)-1-P h en yl-4(Ss)-(p-tolylsu lfin yl)n on -4-
en -3(S)-ol, 3d , 5d . 1H NMR: δ 0.80-0.92 (m, 1 H), 0.93 (t, 3
H, J ) 7.2 Hz), 1.35-1.56 (m, 4 H), 1.92 (m, 1 H), 2.23-2.51
(m, 3 H), 2.43 (s, 3 H), 2.62 (m, 1 H), 3.06 (s, 3 H), 5.19 (dd, 1
H, J ) 10.3, 3.1 Hz), 6.64 (t, 1 H, J ) 7.8 Hz), 6.85 (m, 2 H),
7.14-7.32 (m, 5 H), 7.46 (d, 2 H, J ) 8.2 Hz).
Gen er a l P r oced u r e for SN2′ Ad d ition of Or ga n ocu -
p r a te Rea gen ts to Mesyla tes 4, 5, 12, a n d 13. To a cold
(-78 °C) solution of the organocuprate reagent (formed from
3 equiv of CuI or CuCN and 6 or 3 equiv of the appropriate
organolithium or Grignard reagent, respectively) in THF (20
mL/mmol of mesylate) was added dropwise mesylate 4 or 5 in
THF (5 mL/mmol of mesylate) with vigorous stirring. The
Oxid a tion of Su lfid e 17 to Su lfon e, 15. Following the
above procedure (method A), 17 (0.39 mmol, 110 mg) was
transformed into sulfone 15 which was purified by chroma-
tography on silica gel using CH2Cl2 as eluent (89% yield). This
compound was found to be identical to the sulfone obtained
from the oxidation of sulfoxide 11a (see below). Data of 15:
[R] ) +5.5 (1.29). Rf ) 0.31 (10% EtOAc-hexane). 1H NMR:
δ 0.96 (t, 3 H, J ) 7.4 Hz), 1.41 (d, 3 H, J ) 7.3 Hz), 2.35 (s,
3 H), 2.47-2.74 (m, 2 H), 4.14 (q, 1 H, J ) 7.1 Hz), 6.04 (t, 1
H, J ) 7.7 Hz) 7.04-7.43 (m, 9 H). 13C NMR: δ 13.5, 21.5,
22.3, 22.5, 41.0, 126.4, 127.5, 127.5, 128.4, 129.3, 139.0, 143.5,
143.6, 144.1, 145.8.
Oxid a tion of Su lfoxid e 10a to Su lfon e, 14. Following
the above procedure (method B), 10a (0.07 mmol, 21.4 mg) was

652 J . Org. Chem., Vol. 62, No. 3, 1997
Marino et al.
reaction mixture was allowed to warm up to room temperature
over ca. 5 h after which time a saturated NH4Cl solution was
added. The aqueous layer was extracted with ether (4 × 5
mL/mmol), and the combined organic extracts were washed
with a saturated solution of Na2S2O3 and brine. After drying
(MgSO4) and concentration under reduced pressure, the crude
product was purified by column chromatography on silica gel.
In the case of sulfoxides 2a and 3a , sulfones 12, and sulfides
13, the crude mesylate solution in THF was filtered and
immediately added dropwise to the preformed cuprate solution.
Yields are always given from the initial alcohol.
(E)-2(R)-P h en yl-3(Ss)-(p-tolylsu lfin yl)h ex-3-en e, 8a, an d
(Z)-2(S)-P h en yl-3(Ss)-(p-tolylsu lfin yl)h ex-3-en e, 9a . From
4a and MeCuCNLi, a 6:94 mixture of 8a and 9a was obtained
in 81% yield. An enriched sample of 8a was obtained by
column chromatography, and pure 9a was obtained by recrys-
tallization. Data of 8a : transparent oil. Rf ) 0.24 (20%
EtOAc-hexane). 1H NMR: δ 0.78 (t, 3 H, J ) 7.5 Hz), 1.05
(d, 3 H, J ) 7.4 Hz), 1.85-2.05 (m, 2 H), 2.41 (s, 3 H), 3.87 (q,
1 H, J ) 7.3 Hz), 6.37 (t, 1 H, J ) 7.7 Hz), 7.14-7.30 (m, 7 H),
7.53 (d, 2 H, J ) 8.2 Hz). Data of 9a : white solid. Mp: 74-
76 °C (hexane). [R] ) -313.9 (1.40). Rf ) 0.24 (20% EtOAc-
hexane). 1H NMR: δ 1.13 (t, 3 H, J ) 7.4 Hz), 1.47 (d, 3 H, J
) 7.2 Hz), 2.48 (m, 1 H), 2.81 (m, 1 H), 3.96 (q, 1 H, J ) 7.2
Hz), 5.98 (dd, 1 H, J ) 8.7, 6.6 Hz), 6.62-6.66 (m, 2 H), 6.96-
7.00 (m, 3 H), 7.07-7.10 (m, 2 H), 7.23-7.27 (m, 2 H). 13C
NMR: δ 14.1, 21.2, 22.4, 23.7, 35.2, 124.4, 125.7, 127.1, 127.9,
129.4, 139.6.
(E)-2(S)-P h en yl-3(Ss)-(p-tolylsu lfin yl)h ex-3-en e, 10a, an d
(Z)-2(R)-P h en yl-3(Ss)-(p-tolylsu lfin yl)h ex-3-en e, 11a. From
5a and MeCuCNMgBr, a 6:94 separable mixture of 10a and
11a was obtained in 80% yield. Data of 10a : transparent oil.
Rf ) 0.22 (20% EtOAc-hexane). [R] ) -48.2 (0.56). 1H
NMR: δ 0.87 (t, 3 H, J ) 7.5 Hz), 1.40 (d, 3 H, J ) 7.3 Hz),
1.88-2.15 (m, 2 H), 2.37 (s, 3 H), 3.74 (q, 1 H, J ) 7.3 Hz),
6.40 (t, 1 H, J ) 7.6 Hz), 6.89-7.64 (m, 9 H). 13C NMR: δ
13.0, 19.2, 21.4, 22.2, 35.3, 125.6, 126.9, 128.1, 129.7, 137.2,
140.0, 141.5, 142.5, 147.8. Data of 11a : transparent oil. Rf
) 0.30 (20% EtOAc-hexane). [R] ) -56.4 (1.60). 1H NMR:
δ 0.95 (d, 3 H, J ) 7.2 Hz), 1.05 (t, 3 H, J ) 7.5 Hz), 2.42 (s,
3 H), 2.47-2.70 (m, 2 H), 3.98 (q, 1 H, J ) 7.2 Hz), 5.85 (t, 1
H, J ) 7.6 Hz), 7.14-7.32 (m, 7 H), 7.50 (d, 2 H, J ) 8.2 Hz).
13C NMR: δ 13.9, 21.4, 21.8, 22.3, 34.0, 124.2, 126.1, 127.5,
128.3, 140.1, 140.6, 145.0, 149.9.
(E)-6,6-Dim eth yl-5(R)-ph en yl-4(Ss)-(p-tolylsu lfin yl)h ept-
3-en e, 8e, a n d (Z)-6,6-Dim eth yl-5(S)-p h en yl-4(Ss)-(p-tolyl-
su lfin yl)h ep t-3-en e, 9e. From 4a and t-BuCuCNLi, a 9:91
mixture of 8e and 9e was obtained in 69% yield. Pure 9e and
an enriched sample of 8e were obtained by column chroma-
tography. Data of 8e: transparent oil. Rf ) 0.22 (25%
EtOAc-hexane). 1H NMR: δ 0.99 (t, 3 H, J ) 7.4 Hz), 1.06
(s, 9 H), 2.35 (s, 3 H), 2.39-2.52 (m, 2 H), 2.96 (s, 1 H), 6.54 (t,
1 H, J ) 9.7 Hz), 6.67-6.70 (m, 2 H), 6.95-7.03 (m, 3 H), 7.13
(d, 2 H, J ) 8.1 Hz), 7.43 (d, 2 H, J ) 8.1 Hz). 13C NMR: δ
13.4, 21.3, 23.7, 29.8, 35.9, 56.9, 125.9, 127.4, 127.5, 129.5,
129.7, 134.7, 139.9, 141.9, 143.3. Data of 9e: transparent oil.
[R] ) -123.5 (2.4). Rf ) 0.40 (25% EtOAc-hexane). 1H
NMR: δ 0.95 (s, 9 H), 1.24 (t, 3 H, J ) 7.4 Hz), 2.18 (s, 3 H),
2.62 (m, 1 H), 2.91 (m, 1 H), 3.48 (s, 1 H), 6.66-6.71 (m, 3 H),
6.80-6.94 (m, 5 H), 7.01 (d, 2 H, J ) 8.1 Hz). 13C NMR: δ
14.4, 21.0, 22.6, 28.9, 35.0, 49.5, 124.4, 125.1, 126.8, 128.8,
129.5, 138.4, 139.7, 140.3, 141.2, 146.4.
(m, 1 H), 3.48 (s, 1 H), 6.50 (dd, 1 H, J ) 8.6, 6.6 Hz), 7.15-
7.33 (m, 7 H), 7.49 (d, 2 H, J ) 8.2 Hz). 13C NMR: δ 14.2,
21.3, 22.7, 28.7, 34.3, 50.5, 124.4, 126.0, 127.4, 129.6, 130.1,
138.5, 140.6, 141.6, 146.6.
(E)-5(R)-Meth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-en e, 8b, an d
(Z)-5(S)-Meth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-en e, 9b. From
4b and MeCuCNLi, an inseparable 9:91 mixture of 8b and 9b
was obtained in 86% yield. A small amount of practically pure
9b was obtained by chromatography. Data of 8b: 1H NMR:
δ 0.76 (d, 3 H, J ) 7.2 Hz), 6.36 (t, 1 H, J ) 7.6 Hz). The rest
of the signals could not be measured accurately. Data of 9b:
transparent oil. Rf ) 0.28 (12% EtOAc-hexane). 1H NMR:
δ 0.60 (t, 3 H, J ) 6.7 Hz), 0.70-1.20 (m, 6 H), 1.11 (d, 3 H, J
) 6.9 Hz), 1.14 (t, 3 H, J ) 7.5 Hz), 2.38 (s, 3 H), 2.40-2.54
(m, 1 H), 2.56 (sext, 1 H, J ) 7.2 Hz), 2.65-2.90 (m, 1 H), 5.89
(dd, 1 H, J ) 8.5, 6.9 Hz), 7.26 (d, 2 H, J ) 8.3 Hz), 7.41 (d, 2
H, J ) 8.3 Hz). 13C NMR: δ 13.8, 14.2, 21.2, 22.2, 23.7, 29.0,
29.4, 36.9, 124.2, 129.5, 136.8, 140.1, 140.4, 150.3.
(E)-5(S)-Meth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-en e, 10b,
a n d (Z)-5(R)-Meth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-en e, 11b.
From 5b and Me2CuLi‚LiI, a 90:10 separable mixture of 10b
and 11b was obtained in 80% yield. Data of 10b: transparent
1
oil. Rf ) 0.19 (12% EtOAc-hexane). [R] ) +113.9 (1.10). H
NMR: δ 0.75 (t, 3 H, J ) 7.3 Hz), 0.94 (d, 3 H, J ) 7.1 Hz),
0.96-1.20 (m, 3 H), 1.11 (t, 3 H, J ) 7.5 Hz), 1.20-1.38 (m, 3
H), 2.21 (sext, 1 H, J ) 7.2 Hz), 2.32 (quint, 2 H, J ) 7.6, 1.4
Hz), 2.39 (s, 3 H), 6.35 (t, 1 H, J ) 7.7 Hz), 7.26 (d, 2 H, J )
7.9 Hz), 7.52 (d, 2 H, J ) 7.9 Hz). 13C NMR: δ 13.7, 13.8,
19.7, 21.3, 22.3, 22.4, 29.9, 32.2, 35.8, 125.9, 129.5, 136.0, 140.4,
141.4, 147.5. Data of 11b: transparent oil. Rf ) 0.34 (12%
EtOAc-hexane). [R]) -191.6 (1.13). 1H NMR: δ 0.56 (d, 3
H, J ) 6.9 Hz), 0.86 (t, 3 H, J ) 6.9 Hz), 1.13 (t, 3 H, J ) 7.5
Hz), 1.19-1.38 (m, 5 H), 1.42-1.50 (m, 1 H), 2.38 (s, 3 H),
2.47-2.58 (m, 2 H), 2.70-2.81 (m, 1 H), 5.93 (dd, 1 H, J )
8.5, 6.9 Hz), 7.26 (d, 2 H, J ) 8.1 Hz), 7.42 (d, 2 H, J ) 8.2
Hz). 13C NMR: δ 13.9, 14.1, 21.1, 22.0, 22.3, 22.6, 28.9, 29.3,
38.2, 124.1, 129.5, 137.1, 140.2, 140.5, 150.4.
(E)-1-P h en yl-5(S)-m eth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-
en e, 8d , a n d (Z)-1-P h en yl-5(S)-m eth yl-4(Rs)-(p-tolylsu lfi-
n yl)n on -3-en e, 9d . From 4d and MeCuCNLi, an 8:92 in-
separable mixture of 8d and 9d was obtained in 77% yield. A
small amount of practically pure 9d was obtained by careful
chromatography. Data of 8d : 1H NMR: δ 0.67 (d, 3 H, J )
7.0 Hz), 6.42 (t, 1 H, J ) 7.5 Hz). The rest of the signals could
not be measured accurately. Data of 9d : transparent oil. Rf
) 0.32 (25% EtOAc-hexane). 1H NMR: δ 0.59 (t, 3 H, J )
7.2 Hz), 0.65-1.10 (m, 6 H), 1.08 (d, 3 H, J ) 6.9 Hz), 2.35 (s,
3 H), 2.42 (sext, 1 H, J ) 7.0 Hz), 2.79-2.93 (m, 3 H), 3.03 (m,
1 H), 5.93 (t, 1 H, J ) 7.3 Hz), 7.13-7.38 (m, 9 H). 13C NMR:
δ 13.7, 21.1, 22.2, 23.7, 28.9, 29.7, 30.5, 35.8, 36.8, 124.2, 126.2,
128.5, 128.6, 129.4, 134.4, 139.7, 140.3, 140.6, 151.5.
(E)-1-P h en yl-5(S)-m eth yl-4(Rs)-(p-tolylsu lfin yl)n on -3-
en e, 10d , a n d (Z)-1-P h en yl-5(R)-m eth yl-4(Rs)-(p-tolyl-
su lfin yl)n on -3-en e, 11d . From 5d and Me2CuLi‚LiI, an 85:
15 separable mixture of 10d and 11d was obtained in 85%
yield. Data of 10d : transparent oil. Rf ) 0.15 (25% EtOAc-
hexane). [R] ) +77.9 (1.07). 1H NMR: δ 0.72 (t, 3 H, J ) 6.8
Hz), 0.84 (d, 3 H, J ) 7.1 Hz), 0.86-1.26 (m, 6 H), 2.15 (sext,
1 H, J ) 7.2 Hz), 2.36 (s, 3 H), 2.62 (m, 2 H), 2.81 (m, 2 H),
6.39 (t, 1 H, J ) 7.5 Hz), 7.18-7.31 (m, 7 H), 7.41 (d, 2 H, J )
8.2 Hz). 13C NMR: δ 13.7, 19.4, 21.2, 22.3, 29.8, 30.7, 32.2,
35.3, 35.6, 125.9, 126.1, 128.4, 129.5, 132.2, 140.3, 140.9, 141.4,
148.8. Data of 11d : transparent oil. Rf ) 0.25 (25% EtOAc-
hexane). [R] ) -486.0 (0.35). 1H NMR δ 0.51 (d, 3 H, J ) 7.0
Hz), 0.86 (t, 3 H, J ) 6.8 Hz), 1.19-1.51 (m, 6 H), 2.36 (s, 3
H), 2.47 (sext, 1 H, J ) 7.0 Hz), 2.78-2.90 (m, 3 H), 3.02-
3.08 (m, 1 H), 5.95 (dd, 1 H, J ) 7.9, 6.3 Hz), 7.18-7.35 (m, 9
H). 13C NMR: δ 14.0, 21.2, 22.5, 22.7, 29.3, 29.4, 30.4, 35.9,
38,4, 124.3, 126.3, 128.6, 129.6, 134.8, 140.1, 140.3, 140.7,
151.7.
(E)-6,6-Dim eth yl-5(S)-ph en yl-4(Ss)-(p-tolylsu lfin yl)h ept-
3-en e, 10e, a n d (Z)-6,6-Dim et h yl-5(R)-p h en yl-4(Ss)-(p -
tolylsu lfin yl)h ep t-3-en e, 11e. From 5a and t-BuCuCN-
MgCl, a 6:94 mixture of 10e and 11e was obtained in 71%
yield. Pure 11e and an enriched sample of 10e were obtained
by column chromatography. Data of 10e: transparent oil. Rf
) 0.20 (25% EtOAc-hexane). 1H NMR: δ 1.07 (t, 3 H, J )
7.5 Hz), 1.14 (s, 9 H), 2.26 (s, 3 H), 2.39-2.51 (m, 2 H), 3.80
(s, 1 H), 6.46 (t, 1 H, J ) 7.5 Hz), 6.90-6.97 (m, 4 H), 7.11-
7.19 (m, 5 H). 13C NMR: δ 13.2, 21.1, 23.3, 29.6, 35.8, 55.8,
125.1, 126.5, 128.0, 129.1, 130.3, 139.9, 140.1, 143.3, 148.0.
Data of 11e: white solid. Mp: 134-136 °C. [R] ) -100.1
(1.09). Rf ) 0.29 (25% EtOAc-hexane). 1H NMR: δ 0.59 (s,
9 H), 1.22 (t, 3 H, J ) 7.4 Hz), 2.41 (s, 3 H), 2.60 (m, 1 H), 2.91
(E)-2(S)-P h en yl-3-(p-tolylsu lfon yl)h ex-3-en e, 14, a n d
(Z)-2(R)-P h en yl-3-(p-tolylsu lfon yl)h ex-3-en e, 15. From
the mesylate derived from 12 and Me2CuCN(MgBr)2, a 91:9
mixture of 14 and 15 was obtained in 76% yield. An enriched
sample of 15 was obtained by chromatography, and pure 14
was obtained by recrystallization from hexane. Data of 14:
white solid. Mp: 97-97.5 °C. Rf ) 0.40 (20% EtOAc-hexane).

Carbon-Carbon Bond Formation via SN2′ Displacements
J . Org. Chem., Vol. 62, No. 3, 1997 653
[R] ) -70.1 (1.19). 1H NMR: δ 0.78 (t, 3 H, J ) 7.5 Hz), 1.39
(d, 3 H, J ) 7.3 Hz), 1.72-2.04 (m, 2 H), 2.43 (s, 3 H), 4.04 (q,
1 H, J ) 7.3 Hz), 6.90 (t, 1 H, J ) 7.8 Hz), 7.03-7.77 (m, 9 H).
13C NMR: δ 12.3, 18.1, 21.4, 22.0, 36.4, 126.1, 127.0, 128.1,
128.4, 129.6, 137.1, 142.10, 143.9, 144.0, 145.6. Data of ent-
14 and ent-15 (obtained from ent-12 by the same procedure)
was found to be identical to data of 14 and 15 except for sign
of the optical rotation [R] (ent-14)) +71.1 (1.35).
oil. Rf ) 0.50 (20% EtOAc-hexane). [R] ) -31.0 (0.60). 1H
NMR: δ 0.84-1.00 (m, 6 H), 1.11-1.29 (m, 6 H), 2.30-2.39
(m, 3 H), 2.65 (t, 2 H, J ) 7.4 Hz), 5.13 (tm, 1 H, J ) 9.6 Hz),
5.33 (dt, 1 H, J ) 10.9, 7.0 Hz), 7.30-7.14 (m, 5 H). 13C
NMR: δ 14.1, 21.2, 22.8, 29.4, 29.7, 31.7, 36.2, 37.2, 125.7,
127.1, 128.2, 128.4, 137.2, 142.2.
(E)-5(R)-Meth yl-1-p h en yln on -3-en e, 19. From 11d and
t-BuLi, 19 was obtained in 78% yield. Data of 19: transparent
oil. Rf ) 0.50 (20% EtOAc-hexane). [R] ) -15.5 (0.90). 1H
NMR: δ 0.87 (t, 3 H, J ) 6.6 Hz), 0.92 (d, 3 H, J ) 6.7 Hz),
1.19-1.30 (m, 6 H), 2.02 (br quint, 1 H), 2.25-2.32 (m, 2 H),
2.65 (apt, 2 H, J ) 7.2 Hz), 5.26 (dd, 1 H, J ) 15.3, 7.3 Hz),
5.38 (dt, 1 H, J ) 15.3, 6.2 Hz), 7.13-7.28 (m, 5 H). 13C
NMR: δ 14.1, 20.8, 22.8, 25.0, 29.5, 34.4, 36.2, 36.8, 125.6,
127.3, 128.2, 128.5, 137.3, 142.2.
(E)-2(S)-P h en yl-3-(p-tolylsu lfen yl)h ex-3-en e, 16, a n d
(Z)-2(R)-P h en yl-3-(p-tolylsu lfen yl)h ex-3-en e, 17. From
the mesylate derived from 13 and MeCuCNMgBr a 6:94
mixture of 16 and 17 was obtained in 58% yield. Data of 17:
transparent oil. [R] ) +9.2 (1.67). 1H NMR: δ 0.99 (t, 3 H, J
) 7.5 Hz), 1.41 (d, 3 H, J ) 7.1 Hz), 2.25-2.39 (m, 2 H), 2.30
(s, 3 H), 3.53 (q, 1 H, J ) 7.1 Hz), 5.95 (t, 1 H, J ) 7.0 Hz),
7.02-7.28 (m, 9 H). 13C NMR: δ 13.7, 20.8, 20.9, 23.4, 46.4,
126.2, 127.7, 128.1, 129.5, 129.7, 132.6, 135.7, 137.4, 138.0,
144.7. Data of ent-17 (obtained from ent-13 by the same
procedure) was found to be identical to data of 17 except for
sign of the optical rotation [R] (ent-17) ) -8.8 (1.53).
Gen er a l P r oced u r e for Desu lfin yla tion of Vin yl Su lf-
oxid es. To a cold (-78 °C) 0.4 M Et2O solution of 1 equiv of
vinyl sulfoxide was added MeLi (2 equiv of a 1.6 M Et2O
solution). After 5 min t-BuLi was added (4 equiv of a 1.51 M
pentane solution). When TLC analysis of the crude mixture
showed dissapearance of the starting material (ca. 10 min),
the reaction was quenched with MeOH (200 equiv), diluted
with EtOAc, and washed with a saturated NaCl solution. The
organic extracts were dried over MgSO4 and filtered. Con-
centration under reduced pressure gave a crude product, which
was purified by chromatography on silica gel (5-20% EtOAc-
hexane).
Ack n ow led gm en t. This research was supported by
NIH (CA 22237) and DGICYT (PB93-0154 and PB94-
0104). We thank the Universidad Complutense for a
doctoral fellowship to A.V. We thank the Comunidad
de Madrid for visiting fellowships to A.V. and R.F.P. We
are grateful to Dr. J eff Kampf (Department of Chem-
istry, The University of Michigan) for the X-ray analyses
of 2a , 9a , and 14.
Su p p or tin g In for m a tion Ava ila ble: Additional data for
all new compounds (10 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(Z)-5(S)-Meth yl-1-p h en yln on -3-en e, 18. From 10d and
t-BuLi, 18 was obtained in 78% yield. Data of 18: transparent
J O961292I