Highly Stereoselective Nucleophilic Epoxidation of Simple Vinyl Sulfoxides

Article abstract of DOI:10.1021/jo972358s

The nucleophilic epoxidation of readily available vinyl and dienyl sulfoxides with MOO-t-Bu (M = Li, Na, K) takes place in good yields, with complete preservation of double bond geometry in most cases and with moderate to excellent diastereofacial selectivity to produce enantio- and diastereomerically pure α,β-epoxy sulfoxides, valuable synthetic intermediates. Subsequent straightforward oxidation at sulfur affords the corresponding enantiopure sulfonyl oxiranes. For (1E)-2-sulfinyl dienes, the facial selectivity of this novel process may be controlled by the choice of metal (Li vs Na).

Full text of DOI:10.1021/jo972358s

4954
J . Org. Chem. 1998, 63, 4954-4966
High ly Ster eoselective Nu cleop h ilic Ep oxid a tion of Sim p le Vin yl
Su lfoxid es†
Roberto Ferna´ndez de la Pradilla,*,‡ Sonia Castro,‡ Pilar Manzano,‡ Mar´ıa Mart´ın-Ortega,‡
J ulia´n Priego,‡ Alma Viso,§ Ana Rodr´ıguez,| and Isabel Fonseca|
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva, 3, 28006 Madrid, Spain, Departamento de
Quı´mica Orga´nica I, Facultad de Qu´ımica, Universidad Complutense, 28040 Madrid, Spain, and
Departamento de Cristalografı´a, Instituto de Quı´mica-Fı´sica Rocasolano, CSIC, Serrano 119, 28006
Madrid, Spain
Received December 31, 1997
The nucleophilic epoxidation of readily available vinyl and dienyl sulfoxides with MOO-t-Bu (M )
Li, Na, K) takes place in good yields, with complete preservation of double bond geometry in most
cases and with moderate to excellent diastereofacial selectivity to produce enantio- and diastereo-
merically pure R,â-epoxy sulfoxides, valuable synthetic intermediates. Subsequent straightforward
oxidation at sulfur affords the corresponding enantiopure sulfonyl oxiranes. For (1E)-2-sulfinyl
dienes, the facial selectivity of this novel process may be controlled by the choice of metal (Li vs
Na).
In tr od u ction
In connection with our interest in the development of
sulfur-directed synthetic strategies,6 we required an
efficient route to enantiopure vinyl epoxy sulfoxides of
general structure B, R2 ) vinyl (Scheme 1), with high
regiocontrol, E-Z stereocontrol, and diastereofacial se-
lectivity. Inspection of the literature revealed that while
the chemistry of sulfinyl oxiranes has been thoroughly
studied,7 the existing routes to these intermediates are
somewhat limited. A general approach employs the
condensation between a metalated R-chloro sulfoxide, E,
and an aldehyde to produce an almost equimolar mixture
Asymmetric epoxidations of allylic alcohols and un-
functionalized alkenes are fundamental processes in
contemporary organic synthesis.1,2 In contrast to these
well-established methodologies, there are few protocols
available for effecting asymmetric epoxidations of elec-
tron deficient alkenes, and therefore, this field has been
attracting a great deal of attention in recent years.3 An
alternative approach to enantiopure oxiranes relies on
the diastereoselective epoxidation of an enantiomerically
pure alkene. In this context, J ackson conclusively es-
tablished that the treatment of a variety of enantiopure
(E)-N-(p-tolylsulfonyl) vinyl sulfoximines, available in
four steps from racemic methyl phenyl sulfoxide, with
LiOO-t-Bu produces the corresponding oxiranes with
perfect geometric and facial selectivity and in high
yields.4,5 These oxiranes have been subsequently trans-
formed into a variety of enantiomerically enriched bro-
mohydrins by reaction with MgBr2 and “in situ” reduction
with n-Bu4NBH4.4c
(4) (a) Bailey, P. L.; Clegg, W.; J ackson, R. F. W.; Meth-Cohn, O. J .
Chem. Soc., Perkin Trans. 1 1993, 343-350. For related studies, see:
(b) Briggs, A. D.; J ackson, R. F. W.; Clegg, W.; Elsegood, M. R. J .; Kelly,
J .; Brown, P. A. Tetrahedron Lett. 1994, 35, 6945-6948. (c) Bailey,
P. L.; Briggs, A. D.; J ackson, R. F. W.; Pietruszka, J . Tetrahedron Lett.
1993, 41, 6611-6614.
(5) For leading references on related nucleophilic epoxidations,
see: (a) J ackson, R. F. W.; Turner, D.; Block, M. H. Synlett 1997, 789-
790. (b) Clayden, J .; Nelson, A.; Warren, S. Tetrahedron Lett. 1997,
38, 3471-3474. (c) Evans, P.; Taylor, R. J . K. Tetrahedron Lett 1997,
38, 3055. (d) J ackson, R. F. W.; Palmer, N. J .; Wythes, M. J .; Clegg,
W.; Elsegood, M. R. J . J . Org. Chem. 1995, 60, 6431-6440. (e) J ackson,
R. F. W.; Standen, S. P.; Clegg, W.; McCamley, A. J . Chem. Soc., Perkin
Trans. 1 1995, 141-148. (f) J ackson, R. F. W.; Standen, S. P.; Clegg,
W. J . Chem. Soc., Perkin Trans. 1 1995, 149-156. (g) Linderman, R.
J .; Claassen, R. J ., II.; Viviani, F. Tetrahedron Lett. 1995, 36, 6611-
6614. (h) Yoshimatsu, M.; Gotoh, S.; Gotoh, E.; Tanabe, G.; Muraoka,
O. J . Chem. Soc., Perkin Trans. 1 1997, 3035-3041.
(6) (a) Ferna´ndez de la Pradilla, R.; Mart´ınez, M. V.; Montero, C.;
Viso, A. Tetrahedron Lett. 1997, 38, 7773-7776. (b) Paley, R. S.; de
Dios, A.; Estroff, L. A.; Lafontaine, J . A.; Montero, C.; McCulley, D. J .;
Rubio, M. B.; Ventura, M. P.; Weers, H. L.; Ferna´ndez de la Pradilla,
R.; Castro, S.; Dorado, R.; Morente, M. J . Org. Chem. 1997, 62, 6326-
6343. (c) Viso, A.; Ferna´ndez de la Pradilla, R.; Guerrero-Strachan,
C.; Alonso, M.; Mart´ınez-Ripoll, M.; Andre´, I. J . Org. Chem. 1997, 62,
2316-2317. (d) Marino, J . P.; Viso, A.; Lee, J .-D.; Ferna´ndez de la
Pradilla, R.; Ferna´ndez, P.; Rubio, M. B. J . Org. Chem. 1997, 62, 645-
653. (e) Paley, R. S.; Rubio, M. B.; Ferna´ndez de la Pradilla, R.;
Dorado, R.; Hundal, G.; Mart´ınez-Ripoll, M. Organometallics 1996, 15,
4672-4674. (f) Marino, J . P.; Anna, L. J .; Ferna´ndez de la Pradilla,
R.; Mart´ınez, M. V.; Montero, C.; Viso, A. Tetrahedron Lett. 1996, 37,
8031-8034. (g) Arjona, O.; Ferna´ndez de la Pradilla, R.; Mallo, A.;
Plumet, J .; Viso, A. Tetrahedron Lett. 1990, 31, 1475-1478. (h)
Ferna´ndez de la Pradilla, R.; Montero, C.; Viso, A. Chem. Commun.
1998, 409-410.
* To whom correspondence should be addressed. Tel: 34-(91)-562-
2900 Ext 210. Fax: 34-(91)-564-4853. E-mail: RIF@CC.CSIC.ES.
† Taken in part from the M. S. Theses of S. C., P. M., M. M.-O., and
J . P., Instituto de Qu´ımica Orga´nica, CSIC.
‡ Instituto de Qu´ımica Orga´nica.
§ Universidad Complutense.
| Instituto de Qu´ımica-F´ısica Rocasolano.
(1) For reviews on the asymmetric epoxidation of allylic alcohols,
see: (a) J ohnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed. VCH: New York, 1993; p 103. (b) Katsuki,
T.; Martin, V. S. Org. React. 1996, 48, 1.
(2) For a review on the asymmetric epoxidation of unfunctionalized
alkenes, see: J acobsen, E. N. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed. VCH: New York, 1993; p 159.
(3) For leading references, see: (a) Elston, C. L.; J ackson, R. F. W.;
MacDonald, S. J . F.; Murray, P. J . Angew. Chem., Int. Ed. Engl. 1997,
36, 410-412. (b) Enders, D.; Zhu, J .; Kramps, L. Liebigs Ann./ Recueil
1997, 1101-1113. (c) Adger, B. M.; Barkley, J . V.; Bergeron, S.; Cappi,
M. W.; Flowerdew, B. E.; J ackson, M. P.; McCague, R.; Nugent, T. C.;
Roberts, S. M. J . Chem. Soc., Perkin Trans. 1 1997, 3501-3507. (d)
Allen, J . V.; Cappi, M. W.; Kary, P. D.; Roberts, S. M.; Williamson, N.
M.; Wu, L. E. Ibid. 1997, 3297-3298. (e) Bougauchi, M.; Watanabe,
S.; Arai, T.; Sasai, H.; Shibasaki, M. J . Am. Chem. Soc. 1997, 119,
2329-2330. For a review on applications of polymeric amino acids to
this field, see: (f) Ebrahim, S.; Wills, M. Tetrahedron: Asymmetry
1997, 8, 3163-3173.
(7) For reviews, see: (a) Satoh, T.; Yamakawa, K. Synlett 1992, 455-
468. (b) Satoh, T. Chem. Rev. 1996, 96, 3303-3325. For a leading
reference on the generation of oxiranyllithium reagents from sulfinyl
oxiranes by ligand exchange, see; (c) Satoh, T.; Horiguchi, K. Tetra-
hedron Lett. 1995, 36, 8235-8238.
S0022-3263(97)02358-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/29/1998

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4955
Sch em e 1
Sch em e 2
of this research. Alkenyl sulfoxides A, R1 * H, display a
relatively low reactivity with nucleophiles,14 and the
sulfinyl functionality is labile toward oxidation, either
at the vinyl sulfoxide stage, A, to produce vinyl sulfones
C, which would afford racemic epoxy sulfones D, or at
the sulfinyl oxirane stage, B, leading to scalemic epoxy
sulfones D.15 Considering these potential problems, the
viability and, at best, the facial selectivity of the proposed
epoxidation became a matter of concern. In this paper
we report a full account of our efforts in this field,16 which
have resulted in an efficient and practical methodology
to prepare a variety of optically pure sulfinyl and sulfonyl
oxiranes from readily available alkenyl sulfoxides.
of two diastereomeric chlorohydrins due to low 1,3
asymmetric induction.8 Chromatographic separation fol-
lowed by base-induced cyclization affords the desired
epoxides. Alternatively, a vinyl sulfoxide, A, R1 ) Ph,
R2 ) H, has been treated with aqueous N-bromosuccin-
imide to produce a mixture of bromohydrins with good
selectivity; after separation, the major diastereomer was
transformed into the corresponding epoxide as described
above.9
We perceived that neither existing route was well
suited to our purposes; indeed, the synthesis and subse-
quent metalation of an enantiomerically pure R-chloro
allyl sulfoxide (E, R2 ) vinyl) could be plagued with regio-
and stereochemical problems, including a low configura-
tional stability at sulfur.10 Alternatively, the bromohy-
drin route would require a regioselective electrophilic
addition to the most electron deficient double bond of a
readily available 2-sulfinyl diene system.11 An alterna-
tive approach was then considered, and it was envisioned
that the desired vinyl epoxy sulfoxides B, R2 ) vinyl,
could be obtained by regioselective nucleophilic epoxida-
tion of the most electron deficient double bond of 2-sulfi-
nyl dienes, in close analogy to related findings for
2-sulfonyl dienes.12 Furthermore, the synthetic useful-
ness of enantiopure sulfinyl and sulfonyl oxiranes (B and
D, Scheme 1)5,7,13 prompted us to undertake the develop-
ment of the unprecedented nucleophilic epoxidation of
simple vinyl sulfoxides as a general reaction.
Ep oxid a tion of Vin yl a n d Dien yl Su lfoxid es
To establish if an activated vinyl sulfoxide could
undergo the proposed epoxidation without significant
oxidation to the sulfone, our initial efforts were focused
on keto vinyl sulfoxide 1 (Scheme 2), which afforded a
complex mixture of four diastereomeric epoxides, 2,
presumably geometric and facial isomers. Lowering the
reaction temperature to -78 °C gave a somewhat less
complex mixture but still devoid of synthetic usefulness.
The epoxidation of commercially available phenyl vinyl
sulfoxide 3 was then studied, and a low yield of peroxide
4 was obtained as the only product which could be
characterized from the complex reaction mixtures. In
view of these disappointing results, these examples were
not pursued further. Nonetheless, these experiments had
demonstrated that the reaction conditions were compat-
ible with the sulfinyl functionality, at least for short
reaction times.
Table 1 gathers our results on the epoxidation of simple
E alkenyl sulfoxides 5. Despite extensive experimenta-
tion, phenyl-substituted substrate 5a (Table 1, entries
1-4) was found to be totally unreactive, though forcing
reaction conditions led to variable amounts of epoxy
sulfone 6a , starting material, and the corresponding vinyl
sulfone. Since the lack of reactivity of 5a with nucleo-
philes is well-known,17 we sought to enhance the electron-
withdrawing character of the sulfinyl moiety by means
Two difficulties associated with this approach to sulfi-
nyl oxiranes B (Scheme 1) were apparent at the inception
(8) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J . Org. Chem.
1989, 54, 3130-3136.
(9) (a) Tsuchihashi, G.; Mitamura, S.; Ogura, K. Tetrahedron Lett.
1974, 455-458. For the early reports on the direct Darzens condensa-
tion route to epoxy sulfoxides, see: (b) Tsuchihashi, G.; Ogura, K. Bull.
Chem. Soc. J pn. 1972, 45, 2023-2027. (c) Tavares, D. F.; Estep, R.
E.; Blezard, M. Tetrahedron Lett. 1970, 2373-2376.
(10) Evans, D. A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147-
155.
(11) For a review on sulfinyl dienes, see: Aversa, M. C.; Baratucci,
A.; Bonaccorsi, P.; Gianneto, P. Tetrahedron: Asymmetry 1997, 8,
1339-1367. See also ref 6b.
(12) For selective epoxidations of 2-sulfonyl dienes, see: (a) Ba¨ckvall,
J .-E.; Ericsson, A. M.; J untunen, S.; Na´jera, C.; Yus, M. J . Org. Chem.
1993, 58, 5221-5225. (b) Ba¨ckvall, J .-E.; J untunen, S. J . Org. Chem.
1988, 53, 2398-2400. See also: (c) Hentemann, M. F.; Fuchs, P. L.
Tetrahedron Lett. 1997, 38, 5615-5618.
(13) For a synthesis of Hemibrevetoxin B based on sulfonyl oxiranes,
see: (a) Mori, Y.; Yaegashi, K.; Furukawa, H. J . Am. Chem. Soc. 1997,
119, 4557-4558. For related studies, see: (b)Mori, Y.; Yaegashi, K.;
Furukawa, H. J . Am. Chem. Soc. 1996, 118, 8158-8159. (c) Mori, Y.;
Yaegashi, K.; Kazutaka, I.; Yamamori, Y.; Furukawa, H. Tetrahedron
Lett. 1996, 37, 2605-2608. (d) Mori, Y.; Yaegashi, K.; Furukawa, H.
Tetrahedron 1997, 53, 12917-12932. See also: (e) Takemoto, Y.;
Kuraoka, S.; Ohra, T.; Yonetoku, Y.; Iwata, C. Tetrahedron 1997, 53,
603-616. For an early report on the R-lithiation of sulfonyl oxiranes,
see: (f) Ashwell, M.; Clegg, W.; J ackson, R. F. W. J . Chem. Soc., Perkin
Trans. 1 1991, 897-908.
(14) The Chemistry of Sulphones and Sulphoxides; Patai, S., Rap-
poport, Z., Stirling, C. J . H., Eds.; J ohn Wiley & Sons: New York, 1988.
(15) For the oxidation of sulfoxides with t-BuOOH, see: Breton, G.
W.; Fields, J . D.; Kropp, P. J . Tetrahedron Lett. 1995, 36, 3825-3828.
(16) For a preliminary communication, see: Ferna´ndez de la Pra-
dilla, R.; Castro, S.; Manzano, P.; Priego, J .; Viso, A. J . Org. Chem.
1996, 61, 3586-3587.
(17) Styryl sulfoxides 9a and, especially, 5a undergo conjugate
addition with benzylamine much slower than related, less conjugated,
substrates. See: (a) Pyne, S. G.; Griffith, R.; Edwards, M. Tetrahedron
Lett. 1988, 29, 2089-2092. (b) Pyne, S. G.; Bloem, P.; Griffith, R.
Tetrahedron 1989, 45, 7013-7022. (c) Pyne, S. G.; Bloem, P.; Chap-
man, S. L.; Dixon, C. E.; Griffith, R. J . Org. Chem. 1990, 55, 1086-
1093.

4956 J . Org. Chem., Vol. 63, No. 15, 1998
Ta ble 1. Ep oxid a tion of E Vin yl Su lfoxid es
Ferna´ndez de la Pradilla et al.
entry
substrate
R
R1
p-Tol
M
time (min)
sulfonea
R-epoxidea
â-epoxidea
yieldb (%)
1
2c
3
4
5
5a
5a
5a
5a
5b
5c
5c
5c
5d
5e
5e
5f
Ph
Ph
Ph
Ph
Ph
Li
Li
Na
K
Li
Li
Na
K
3 days
7 h
270
300
1 day
240
90
9
220
6a (63)
6a (17)
6a (91)
6a (24)
-
6c (25)
6c (13)
6c (-)
6d (2)
6e (1)
6e (13)
6f (8)
-
-
-
-
p-Tol
p-Tol
p-Tol
o-NO2-Ph
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
t-Bu
-
-
-
-
-
-
-
-
-
-
NR
70
75
65
67
-
6
n-Bu
n-Bu
n-Bu
(CH2)2Ph
t-Bu
7c (58)
7c (83)
7c (94)
7d (97)
7e (10)
7e (37)
7f (82)
8c (17)
8c (4)
8c (6)
8d (1)
-
7
8d
9
Na
Na
K
10e
11f
12g
5 days
3 days
75 h
t-Bu
n-Bu
-
-
87
65
K
a
1
Ratios of products measured by integration of the 300 MHz H NMR spectra of crude reaction mixtures are in parentheses.
Unoptimized combined yields of pure products. c Reaction conducted in Et2O. Reaction conducted with 2 equiv of KOO-t-Bu. e Starting
b
d
material detected in crude reaction mixture (89% ratio). f Starting material detected in crude reaction mixture (50% ratio). Starting
g
material detected in crude reaction mixture (10% ratio).
of an o-nitrophenyl substituent.18 Unfortunately, sub-
strate 5b was found to be strikingly unreactive with
LiOO-t-Bu (Table 1, entry 5) and led to complete decom-
position with NaOO-t-Bu.
dation of racemic 5f, the tert-butyl sulfoxide analogue of
5c,19 was studied, and a fair yield of oxirane 7f was
obtained in a somewhat sluggish reaction (Table 1, entry
12).
A simple alkyl-substituted substrate, 5c, was studied
next, and our initial efforts led to almost exclusive
formation of sulfone 6c. After screening the qualitative
influence of stoichiometry, temperature, concentration,
and time on the reaction, the desired epoxy sulfoxides
7c and 8c, were obtained albeit in low selectivity and
along with substantial amounts of sulfone 6c (Table 1,
entry 6). It should be pointed out that in most cases,
very careful monitoring of the reaction by TLC was
crucial since vinyl and epoxy sulfoxides present very
similar chromatographic mobilities; in addition, the
reaction temperature was also found to be a key factor
to the success of the process with 0 °C showing the best
balance between the rates of epoxidation and undesired
overoxidation. In an attempt to improve the yield and
selectivity of this process, the effect of the metal cation
was examined. The use of NaOO-t-Bu, generated from
oil free NaH, resulted in a substantial enhancement of
the reaction rate and selectivity, along with less over-
oxidation to the sulfone (Table 1, entry 7). Finally, the
use of KOO-t-Bu, generated from oil free KH, produced
a very fast reaction with good stereoselectivity but in
slightly lower yield than with NaOO-t-Bu. It should be
pointed out that, to the best of our knowledge, NaOO-t-
Bu has not been used before for related processes, and it
may be the reagent of choice for epoxidations of moder-
ately reactive substrates.
The effect of the alkene geometry on the process was
then addressed, and the results obtained for a variety of
Z vinyl sulfoxides, 9, are shown in Table 2. Phenyl-
substituted sulfoxide 9a produced R-epoxide 11a in high
yield and with excellent facial selectivity with either
lithium or, even better, the sodium reagents (Table 2,
entries 1 and 2). In addition, overoxidation to the sulfone
was hardly a problem in these cases. It should be
mentioned that the minor isomer obtained, which we
originally assigned as a cis-â-epoxide,16 was later found
to be the elusive trans-R-isomer, 7a (Table 1).
Entries 3-5 illustrate the remarkable selectivity found
for substrates bearing Me and n-Bu substituents at the
â-carbon. Furthermore, high yields and selectivities were
also obtained for i-Pr- and even t-Bu-substituted alkenyl
sulfoxides 9d and 9e (Table 2, entries 6-8). The pos-
sibility of using tert-butyl sulfoxides was also examined
with excellent results for the Z geometrical isomer, 9f
(Table 2, entry 9). Finally, sulfinyl oxirane 11g, immedi-
ate precursor of a key component of Mori’s recent
Hemibrevetoxin B synthesis,13a was prepared in a short
(four steps from 1,4-butanediol) and highly stereocon-
trolled sequence.
To determine the scope of the methodology, the epoxi-
dation of more highly substituted substrates was ex-
plored, and the results obtained are shown in Scheme 3.
To our dismay, both 13 and 14, representative examples
of R,â-disubstituted vinyl sulfoxides, were found to be
completely unreactive under a number of experimental
conditions. It should be noted that a dramatic loss of
reactivity has been reported for related R,â-disubstituted
vinyl sulfones and sulfoximines.5h,4a At this stage of the
project, the reactivity of phenyl-substituted substrates
The nucleophilic epoxidation of alkenyl sulfoxide 5d
(Table 1, entry 9) led to crystalline oxirane 7d as
practically a single isomer. Entries 10 and 11 (Table 1)
show that the process is viable, though not synthetically
useful at this stage, even when the â-carbon is highly
hindered by a tert-butyl substituent. Finally, the epoxi-
(18) o-Nitrophenyl ethynyl sulfoxides display an enhanced reactivity
with nucleophiles relative to their p-tolyl analogues. See: (a) Lee, A.
W. M.; Chan, W. H. Topics Curr. Chem. 1997, 190, 103-129. (b) Lee,
A. W. M.; Chan, W. H.; Tao, Y.; Lee, Y. K. J . Chem. Soc., Perkin Trans.
1 1994, 477-481.
(19) The use of tert-butyl sulfoxides allows for improved stereocontrol
vs their p-tolyl analogues in some cases. For the preparation of
optically pure tert-butyl sulfoxides, see: Khiar, N.; Ferna´ndez, I.;
Alcudia, F. Tetrahedron Lett. 1994, 35, 5719-5722, and references
therein.

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4957
Ta ble 2. Ep oxid a tion of Z Vin yl Su lfoxid es
entry
substrate
R
R1
M
time (min)
sulfonea
R-epoxidea
â-epoxidea
yieldb (%)
1c
2d
3
9a
9a
9b
9b
9c
9d
9d
9e
9f
Ph
Ph
Me
Me
n-Bu
i-Pr
i-Pr
t-Bu
n-Bu
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
t-Bu
Li
Na
Li
Na
Li
Na
K
Na
Li
Na
240
30
150
100
20
2 days
1 day
1 day
210
25
10a (6)
10a (3)
10b (6)
-
11a (86)
11a (96)
11b (92)
11b (98)
11c (98)
11d (85)
11d (73)
11e (85)
11f (98)
11g (92)
-
84
89
63
80
74
90
87
81
79
77
-
12b (2)
12b (2)
12c (2)
12d (2)
12d (1)
12e (2)
12f (2)
12g (2)
4
5
-
6e
7f
8g
9
10d (13)
10d (3)
10e (3)
-
10h
9g
(CH2)3OTBDPS
p-Tol
10g (1)
a
Ratios of products measured by integration of the 300 MHz 1H NMR spectra of crude reaction mixtures are in parentheses.
Unoptimized combined yields of pure products. c Trans oxirane 7a detected in crude reaction mixture (8% ratio). Trans oxirane 7a
b
d
detected in crude reaction mixture (1% ratio). e Reaction conducted with 6 equiv of NaOO-t-Bu. f Starting material detected in crude
g
h
reaction mixture (23% ratio). Starting material detected in crude reaction mixture (10% ratio). Corresponding allyl sulfoxide detected
in crude reaction mixture (5% ratio).
Sch em e 3
Sch em e 4
ity. Finally, the reactivity of vinyl stannane 216b was
examined, and complex mixtures of starting material and
destannylated oxiranes 6c, 7c, and 8c, identical to those
derived from 5c (Table 1, entries 6 and 7), were obtained.
The reversal of selectivity found for the epoxidation of
21 with LiOO-t-Bu (7c:8c, 1:2.3), relative to 5c (7c:8c,
3.4:1), suggests that, at least to some extent, cleavage of
the tin-carbon bond took place after epoxidation had
occurred. Therefore, it appears that substitution at the
R-position can significantly alter the facial selectivity of
the epoxidation with LiOO-t-Bu for this geometry.
The influence of an additional substituent at the
â-carbon was examined next, and the results obtained
for the epoxidation of 22 are shown in Scheme 4. Not
too unexpectedly, 22 was found to be significantly less
reactive than the disubstituted alkenes studied in Tables
1 and 2. Indeed, LiOO-t-Bu led to low conversions, and
prolonged reaction times afforded mixtures of starting
material and epoxy sulfone 23. On the other hand,
NaOO-t-Bu led to higher conversions, but complex mix-
tures of products 23-26, including an allylic sulfoxide,
26, were also obtained; therefore, this case was not
studied in more detail.
15 and 18 was examined. Our selection of these sub-
strates was dictated by concurrent results on preliminary
epoxidations of 2-sulfinyl dienes. However, a clean
epoxidation of E isomer 15 could not be achieved; instead,
variable mixtures of starting material, epoxy sulfone 16,
and small amounts of epoxy sulfoxide 17 were obtained.
Moreover, the use of KOO-t-Bu produced even more
complex mixtures of the above compounds and allylic
sulfoxides. In sharp contrast, the Z isomer 18 led to
oxiranes 19 and 20 in good yields and with high selectiv-
Table 3 is composed of our efforts on the epoxidation
of cyclic substrates 27. The simple cyclohexenyl sulfoxide
27a led to variable mixtures of starting material, vinyl
sulfone, and epoxy sulfone (Table 3, entries 1 and 2). For
this substrate, the use of KOO-t-Bu produced even more
complex mixtures of the above compounds and the
corresponding allylic sulfoxide. In contrast, the more

4958 J . Org. Chem., Vol. 63, No. 15, 1998
Ta ble 3. Ep oxid a tion of Cyclic Vin yl Su lfoxid es
Ferna´ndez de la Pradilla et al.
entry
substrate
X
n
M
time (min)
sulfonea
R-epoxidea
â-epoxidea
yieldb (%)
1c
2d
3
27a
27a
27a
27b
27b
27b
27b
27c
H, H
H, H
H, H
O
O
O
1
1
1
1
1
1
1
0
Li
Na
K
Na
Na
Li
Li
Li
26 h
31 h
510
17
40
10
28a (19)
28a (35)
-
-
-
-
-
trace
see text
29b (36)
29b (44)
29b (9)
29b (15)
29c (40)
4e
5f
6e
7g
8h
-
-
-
-
-
30b (64)
30b (56)
30b (91)
30b (85)
30c (60)
44
-
48
-
O
O
240
5
47
a
Ratios of products measured by integration of the 300 MHz 1H NMR spectra of crude reaction mixtures are in parentheses.
Unoptimized combined yields of pure products. c Starting material (42% ratio) and vinyl sulfone (39% ratio) detected in crude reaction
b
mixture. Starting material (42% ratio) and vinyl sulfone (13% ratio) detected in crude reaction mixture. e Reaction conducted at -78
d
°C. f Reaction performed by adding a solution of a 1:1 mixture of 27b and ZnBr2 to a cold (-78 °C) solution of NaOO-t-Bu. Reaction
g
performed by adding a solution of LiOO-t-Bu to a cold (-78 °C) solution of a 1:1 mixture of ZnBr2 and 27b and subsequent slow warming
h
to room temperature. Two equivalents of LiOO-t-Bu used.
Ta ble 4. Ep oxid a tion of (1E)-2-Su lfin yl Dien es
entry
substrate
R
M
time (min)
sulfonea
R-epoxidea
â-epoxidea
yieldb (%)
1
2
3
31a
31a
31b
31b
31b
31c
31c
31d
H
H
Ph
Ph
Ph
Li
Na
Li
Na
Na
Li
Na
Li
120
90
2 h
45
-
33a (20)
33a (84)
33b (12)
33b (64)
33b (77)
trace
34a (80)
34a (8)
34b (86)
34b (27)
34b (16)
-
75
61
74
76
74
-
32a (8)
32b (2)
32b (9)
32b (7)
-
4
5c
6
15
CH2OH
CH2OH
CH2OTBDPS
26 h
120
27 h
7
32c (3)
-
33c (97)
33d (15)
-
80
-
8d
34d (5)
a
Ratios of products measured by integration of the 300 MHz 1H NMR spectra of crude reaction mixtures are in parentheses.
Unoptimized combined yields of pure products. c Reaction conducted at -20 °C. Starting material detected in crude reaction mixture
(80% ratio).
b
d
activated keto sulfoxide 27b underwent smooth epoxi-
dation even at -78 °C, albeit in low yields (Table 3,
entries 4-7). While in this case, with NaOO-t-Bu, even
in the presence of ZnBr2, the selectivity found was poor,
the use of LiOO-t-Bu resulted in an acceptable ratio in
favor of the â isomer. In a final attempt to alter the
stereochemical outcome of the process, an inverse addi-
tion protocol with LiOO-t-Bu and ZnBr2 was carried out;
this experiment resulted in a slight decrease in selectivity
and very slow reaction rate (compare entries 6 and 7,
Table 3). The five-membered ring analogue 27c under-
went a smooth reaction to produce epoxides 29c and 30c
in low isolated yield and with marginal facial selectivity.
the desired transformation in high yield and with almost
perfect selectivity (Table 4, entries 6-8).
Table 5 is composed of our efforts on the epoxidation
of (1Z)-2-sulfinyl dienes 35. Entry 1 shows the results
obtained for the simple diene 35a , under standard
conditions using LiOO-t-Bu. A pronounced solvent effect
was found (Table 5, entries 2-4) for this epoxidation;
thus, while the use of the more polar solvent DME led to
a very slow reaction with comparable selectivity to THF,
the use of diethyl ether produced exclusively epoxy
sulfone 36a in high yield and with ca. 84% ee. The
optical purity of this sulfone was determined by com-
parison of the optical rotation of 36a (entry 3, [R] )
+82.8), with that of an enantiomerically pure sample ([R]
) +99.5) obtained by oxidation (Oxone, MeOH) of sulfinyl
epoxide 37a . This observation suggests that in ether the
reaction occurs with better selectivity (ca. 90:10) than in
THF, and that sulfoxides 37a and 38a are oxidized very
readily in ether. Entry 4 shows the best product distri-
bution obtained after an extensive study directed to
control this undesired oxidation in ether. Fortunately,
the use of NaOO-t-Bu in THF allowed for a substantial
enhancement of selectivity and in a straightforward
The epoxidation of 2-sulfinyl dienes was examined
next, and the results obtained for the 1E isomers 31 are
shown in Table 4. Entries 1 and 2 indicate that the metal
cation plays a crucial role in determining the facial
selectivity of this process. A similar reversal of selectivity
was found for substrate 31b (Table 4, entries 3-5). The
epoxidation of diene 31c, bearing a free hydroxyl func-
tionality, with LiOO-t-Bu was not effective, and protec-
tion as a TBDPS ether gave very low conversions of
epoxides 33d and 34d . In contrast, NaOO-t-Bu produced

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4959
Ta ble 5. Ep oxid a tion of (1Z)-2-Su lfin yl Dien es
entry
substrate
R
R1
M
time (min)
sulfonea
R-epoxidea
â-epoxidea
yieldb (%)
1
35a
35a
35a
35a
35a
35b
35c
35c
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Li
Li
Li
Li
Na
Na
Li
120
21 h
120
72 h
25
90
24 h
160
-
37a (77)
37a (43)
-
37a (76)
37a (95)
37b (98)
37c (58)
37c (92)
38a (23)
38a (14)
-
38a (6)
38a (5)
-
38c (28)
38c (5)
83
-
2c
3d
4e
5
-
36a (100)
36a (18)
-
36b (2)
36c (12)
36c (3)
92
-
81
94
-
6
7
8
CH2OH
H
H
Na
60
a
Ratios of products measured by integration of the 300 MHz 1H NMR spectra of crude reaction mixtures are in parentheses.
Unoptimized combined yields of pure products. c Reaction conducted in DME, starting material (43% ratio) detected in crude reaction
b
mixture. Reaction conducted in Et2O, sulfone 36a had 84% ee. e Reaction conducted in Et2O at -28 °C.
d
Sch em e 5
Sch em e 6
our vinyl sulfinyl oxiranes (33a and 34a , Table 4; 37a
and 38a , Table 5) was pursued. It was envisioned that
the application of Yamakawa’s methodology,7,8 of known
stereochemical outcome, to n-propyl p-tolyl sulfoxide 39
and n-pentanal should lead to two diastereomeric oxi-
ranes which would be either enantiomeric or diastereo-
meric to those obtained by hydrogenation of our vinyl
sulfinyl oxiranes. Thus, 39 was smoothly chlorinated to
yield an inseparable mixture of chloro sulfoxides 40
(Scheme 6) which were lithiated and treated with n-
pentanal to afford an almost equimolar mixture of
chlorohydrins 41 and 42; these were separated by chro-
matography and cyclized by treatment with KO-t-Bu to
produce sulfinyl epoxides 43 and 44.
The hydrogenation of our vinyl oxiranes 34a and 37a
(Scheme 7) was then addressed. After several fruitless
attempts to carry out catalytic hydrogenations (H2, Pd/
C, EtOH) which gave rise to complex mixtures, including
products of allylic rearrangement,20 the use of diimide
produced the desired saturated sulfinyl oxiranes ent-44
and 45.21 It should be pointed out that 43 and 45 had
manner (Table 5, entry 5). These conditions were also
optimal for diene 35b with a free hydroxyl substituent,
as well as, remarkably, for diene 35c, with a fully
substituted â-carbon (Table 5, entries 6 and 8).
Str u ctu r a l Assign m en ts
The structure of these sulfinyl oxiranes was derived
from their spectral features. To conclusively prove the
oxidation state at sulfur and our ability to prepare
sulfonyl oxiranes, several oxidations for representative
substrates under standard conditions were carried out,
and the results obtained are shown in Scheme 5. These
oxidations proceeded smoothly and in good yields to
produce a variety of epoxy sulfones; the chemoselectivity
found for 33b and 37a is noteworthy and allows for a
straightforward preparation of enantiomerically pure
acyclic vinyl epoxy sulfones, regioisomeric to the cyclic
epoxy vinyl sulfones described by Fuchs.12c
(20) This observation suggests that these vinyl oxiranes could be
adequate substrates for π-allyl palladium chemistry. This possibility
is being pursued in our laboratory.
(21) For a review, see: Pasto, D. J .; Taylor, R. J . K. Org. React. 1991,
40, 91-155.
With a secure assignment of the oxidation state at
sulfur, the clarification of the relative configuration of

4960 J . Org. Chem., Vol. 63, No. 15, 1998
Ferna´ndez de la Pradilla et al.
Sch em e 7
assign the structure of our major cis oxirane 11a .
Therefore, a more definitive structural proof was sought
and an X-ray diffraction analysis of 11a was carried out
(Supporting Information); this analysis confirmed our
initial tentative assignment.16
At this stage of the project the results of Tavares et
al.,9c on the condensation between chloro sulfoxide 46 and
benzaldehyde, were examined, in an attempt to clarify
the selectivity of that process. It should be pointed out
that the original report mentioned a cis oxirane as the
main product, along with some trans oxirane, but the
ratio of products and the relative stereochemistries were
not discussed. In our hands, this reaction afforded a low
yield (44% unoptimized) of a 21:73:6 mixture of sulfinyl
epoxides ent-8a , ent-12a , and ent-7a (Scheme 8).22
With regard to the epoxidation of simple E vinyl
sulfoxides (Table 1), the major products had been tenta-
tively assigned as â-epoxides,16 in analogy with our own
preliminary results for (1E)-dienes with LiOO-t-Bu (Table
4, entry 1) and with some literature precedents on
nucleophilic additions to alkenyl sulfoxides.23 However,
some results obtained at a later stage of this project24
made us question the accuracy of our previous assign-
ment. To clarify this issue, an X-ray diffraction analysis
of trans sulfinyl oxirane 7d was carried out (Supporting
Information); this analysis unequivocally showed an
R-epoxide structure for 7d .
Sch em e 8
Our stereochemical assignment for cyclic keto sulfinyl
oxiranes 29 and 30 (Table 3) is tentative and relies on
comparison of the 1H NMR chemical shifts of the oxirane
protons of 29b and 30b with those of related acyclic
substrates 7c/8c (Table 1) and 33a /34a (Table 4), for
which the â-epoxides had slightly more deshielded oxi-
rane protons (∆δ ) 0.12 and 0.05 ppm, respectively). In
addition, the â-epoxides 8c and 34a showed a slightly
higher chromatographic mobility (∆Rf ) 0.05 and 0.03,
respectively), comparable to the behavior found for 30b
relative to 29b (∆Rf ) 0.07). Finally, in the presence of
ZnBr2, a small but significant enhancement of R selectiv-
ity was found; this observation is consistent with Posner’s
results on additions of carbon-centered nucleophiles to
these systems.25
spectral data that clearly indicated a cis geometry and a
diastereomeric nature. In contrast, 44 and ent-44 had
identical spectral features and optical rotations of op-
posite sign (-53.6 and +52.1, respectively), thus indicat-
ing an enantiomeric relationship.
Resu lts a n d Discu ssion
The stereochemical outcome of the nucleophilic epoxi-
dation of simple vinyl and dienyl sulfoxides with NaOO-
t-Bu or KOO-t-Bu may be rationalized in terms of an
initial nucleophilic addition to the R-face of reactive
conformation A (Scheme 9), with an s-trans coplanar
arrangement of SdO and CdC bonds, followed by epoxide
To carry out a comparable correlation for our simple
oxiranes (Tables 1 and 2) the condensation between
lithiated chloromethyl sulfoxide 468 and benzaldehyde
was explored. To our dismay, a low yield of an insepa-
rable mixture of three diastereomeric chlorohydrins 47-
49 was obtained (Scheme 8). The subsequent cyclization
proceeded smoothly and trans epoxide ent-8a (J 2,3 ) 1.7
Hz) was separated from the mixture of cis epoxides ent-
12a (J 2,3 ) 3.4 Hz) and ent-11a (J 2,3 ) 3.7 Hz). Since
reliable spectral data for three of the four possible
diastereomeric oxiranes bearing a phenyl substituent was
now available, by exclusion, the correct structure for 7a
(4.70 ppm, s, 2 H, H-2, H-3) (Table 2, entry 1) had to be
the one shown, an R-trans oxirane, which may be formed
by â-attack of LiOO-t-Bu to Z vinyl sulfoxide 9a , followed
by rotation around the C-2/C-3 bond and oxirane ring
closure. However, it was considered that the low yield
and selectivity found rendered this route unreliable to
(22) We have also reproduced the results of Tsuchihashi (ref 9a) on
the treatment of E sulfoxide 5a with aqueous NBS and subsequent
base-induced cyclization of the major bromohydrin to produce oxirane
8a ; however, an attempt to apply this protocol to Z sulfoxide 9a led to
a low conversion (ca. 25% after 4 h) of an equimolar mixture of
bromohydrins.
(23) For additions of malonate anions to 5a and 9a , see: (a)
Tsuchihashi, G.; Mitamura, S.; Ogura, K. Tetrahedron Lett. 1976, 855-
858. (b) See ref 17c.
(24) These include the reversal of diastereoselectivity found for 1E
sulfinyl dienes 31a and 31b and stannane 21 upon a change in the
metal from Li to Na, as well as the stereochemical outcome of the
epoxidation of related R-(1-hydroxyalkyl) and γ-oxygenated vinyl
sulfoxides, see: Ferna´ndez de la Pradilla, R.; Manzano, P.; Priego, J .;
Viso, A.; Mart´ınez-Ripoll, M.; Rodr´ıguez, A. Tetrahedron Lett. 1996,
37, 6793-6796.
(25) Posner, G. H. Acc. Chem. Res. 1987, 20, 72-78, and references
therein.

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4961
repulsion,25 and the use of LiOO-t-Bu further increases
the relative participation of conformer C, as discussed
above.
Sch em e 9
Con clu sion s
A novel methodology to effect the nucleophilic epoxi-
dation of vinyl and dienyl sulfoxides has been developed.
The scope of this protocol has been defined, and in this
fashion, a variety of enantiopure epoxy sulfoxides and
epoxy sulfones are now readily available by short and
highly stereocontrolled sequences. Of the different sub-
stitution patterns studied, the simple Z vinyl sulfoxides
9, and (1E)- or (1Z)-2-sulfinyl dienes 31 and 35, are
particularly good substrates for this process. In most
cases, the geometry of the starting materials is fully
transferred to the resulting oxiranes, and the reaction
occurs in good yields and with good to excellent facial
selectivity. The possibility of controlling the diastereo-
selectivity of the epoxidation of (1E)-2-sulfinyl dienes by
a simple change in the metal cation (Li to Na) is
remarkable. Additional extensions of this unique meth-
odology as well as applications to the synthesis of natural
products are being pursued in our laboratory.
ring closure. In these cases, we believe that steric
hindrance by the bulky tolyl group is the main factor
behind the high stereoselectivity found. With regard to
epoxidations with LiOO-t-Bu, most cases studied show
a diminished R selectivity relative to Na or KOO-t-Bu.
This trend is particularly important for E vinyl sulfox-
ides, and it suggests a larger degree of â-attack to
reactive conformation B, in which the SdO and CdC
bonds are syn coplanar. Alternatively, conformation C,
which places the sulfinyl oxygen above the plain of the
alkene, could be operative by promoting coordination of
the sulfinyl oxygen with lithium and thus placing the
nucleophilic peroxide moiety at the â-face and in close
proximity to the reactive site. This larger participation
of conformation B or C for E alkenyl sulfoxides may be
attributed to a diminished allylic 1,3-strain between the
sulfinyl moiety and the cis hydrogen relative to the cases
were R1 * H.26
Further pieces of evidence in favor of a reaction
pathway involving sulfinyl oxygen coordination with
lithium are the lack of reactivity found for dienes 31c
and 31d with LiOO-t-Bu (Table 4, entries 6 and 8) and
the observed reversal of facial selectivity found for 1E
diene 31a (R2 ) vinyl, R3 ) n-Bu) and stannane 21 (R2
) n-Bu3Sn, R3 ) n-Bu) upon a change of the metal. In
these cases, NaOO-t-Bu yields predominantly the R-ox-
irane, perhaps via reactive conformer A (R1 ) H), and
LiOO-t-Bu gives a moderately â-selective process, pre-
sumably via coordination of lithium to the sulfinyl oxygen
and counterclockwise rotation about the C-S bond to
yield reactive conformer C. The related clockwise rota-
tion is likely to suffer a severe steric interaction between
the p-tolyl moiety and the R2 substituent due to allylic
1,2-strain. For the 1Z diene isomer 35a (R1 ) n-Bu, R2
) vinyl, R3 ) H), allylic 1,3-strain between the sulfinyl
moiety and R1 precludes the counterclockwise rotation
mode from being dominant, and the experimental result
with LiOO-t-Bu is just a decrease of R-selectivity.
With regard to cyclic keto sulfoxide 27b, the results
obtained with NaOO-t-Bu may reflect an enhanced
participation of conformer B due to CdO/SdO dipole
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. All reactions were carried out
under a positive pressure of dry argon, using freshly distilled
solvents under anhydrous conditions. Reagents and solvents
were handled by using standard syringe techniques. Et2O and
THF were distilled from sodium and benzophenone. Crude
products were purified by flash chromatography on Merck
230-400 mesh silica gel with distilled solvents. Analytical
TLC was carried out on Merck (Kieselgel 60F-254) silica gel
plates with detection by UV light, iodine, acidic vanillin
solution, 10% phosphomolybdic acid solution in ethanol, and
15% KMnO4 in water containing 5% NaOH and 10% K2CO3.
All reagents were commercial products purchased from Ald-
rich, Fluka, or Merck. Commercially available organometallic
reagents were used: n-BuLi (solution in hexane) was titrated
before use.27 Infrared spectra (IR) were obtained on a Perkin-
Elmer 681. 1H and 13C NMR spectra were recorded at 200 or
300 MHz (1H) using CDCl3 as solvent and with the residual
solvent signal as internal reference (CDCl3, 7.24 and 77.0
ppm). The following abbreviations are used to describe peak
patterns when appropriate: s (singlet), d (doublet), t (triplet),
q (quartet), quint (quintuplet), sext (sextet), m (multiplet), ap
(apparent), br (broad). Melting points are uncorrected. Opti-
cal rotations were measured at 20 °C using a sodium lamp
and in CHCl3 solution. The vinyl sulfoxides used in this study
were prepared by literature methods: 1;6d 5a , 9a , 5b, 9b;28
5c;29 9c, 9d , 9e, 9g;30 5d ;30,31 5e;31 9f, 5f;31,32 13;31 14;33 15, 18,
(27) Watson, S. C.; Eastham, J . E. J . Organomet. Chem. 1967, 9,
165-168.
(28) Andersen, K. K. Tetrahedron Lett. 1962, 93-96.
(29) Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J .
Org. Chem. 1987, 52, 1078-1082.
(30) (a) Craig, D.; Daniels, K.; McKenzie, A. R. Tetrahedron 1993,
49, 11263-11304. Vinyl sulfoxide 9g was prepared from 4-[(tert-
butyldiphenylsilyl)oxy]-1-butanal, available in two steps from 1,4-
butanediol (1. NaH, THF, t-BuPh2SiCl, 87%. 2. PCC, NaOAc, CH2Cl2,
84%). See: (b) McDougal, P. G.; Rico, J . G.; Oh, Y.-I.; Condon, B. D.
J . Org. Chem. 1986, 51, 3388-3390.
(31) (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. (c) Fawcett, J .; House, S.; J enkins, P.
R.; Lawrence, N. J .; Russell, D. R. J . Chem. Soc., Perkin Trans.1 1993,
67-73.
(32) Free radical addition of 2-methyl-2-propanethiol to 1-hexyne
and oxidation with m-CPBA. See: J acobs, T. L.; Illingworth, G. E. J .
Org. Chem. 1963, 28, 2692.
(26) For a review, see: (a) Hoffman, R. W. Chem. Rev. 1989, 89,
1841-1860. See also: (b) Koizumi, T.; Arai, Y.; Takayama, H.;
Kuriyama, K.; Shiro, M. Tetrahedron Lett. 1987, 28, 3689-3692.

4962 J . Org. Chem., Vol. 63, No. 15, 1998
Ferna´ndez de la Pradilla et al.
21;6b 22;34 27a ;35 27b, 27c;36 31a , 31b, 31c, 35a , 35b, 35c;6b
39;28 46.8
round-bottomed flask fitted with a T-tube for entrance and exit
of argon and a polyethylene stopper was charged with anhy-
drous THF (10 mL/mmol) and 4 equiv of t-BuOOH (80% in
t-BuOO-t-Bu, Fluka), the mixture was cooled to 0 °C, and then
5 equiv of n-BuLi was added. The mixture was stirred at 0
°C for 10 min, and a solution of 1 equiv of the corresponding
vinyl sulfoxide in THF (10 mL/mmol), previously dried over 4
Å sieves, was added dropwise. The reaction mixture was
stirred at 0 °C until starting material disappearance, moni-
tored by TLC. The reaction was then quenched with a
saturated solution of Na2S2O4 (4 mL/mmol) and diluted with
EtOAc (8 mL/mmol), and the layers were separated. The
aqueous layer was extracted with EtOAc (three times), and
the combined organic extracts were washed with a saturated
solution of NaCl (4 mL/mmol), dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure to give a
crude product, which was purified by column chromatography
on silica gel, using the appropriate mixture of EtOAc-hexane.
(b) With Na OO-t-Bu or KOO-t-Bu . A two-necked round-
bottomed flask fitted with a T-tube for entrance and exit of
argon and a polyethylene stopper was charged with anhydrous
THF (10 mL/mmol) and 4 equiv of oil free NaH or KH (washed
with hexane and dried), the mixture was cooled to 0 °C, and
then 4 equiv of t-BuOOH (80% in t-BuOO-t-Bu) was added.
After stirring at 25 °C for 20-30 min, the resulting solution
was cooled to 0 °C, and a solution of 1 equiv of the correspond-
ing vinyl sulfoxide in THF (10 mL/mmol), previously dried over
4 Å sieves, was added dropwise. The reaction mixture was
stirred at 0 °C until starting material disappearance, moni-
tored by TLC. Isolation and purification were performed as
described above. In some cases 2 equiv of KH/t-BuOOH was
used.
Syn t h esis of (+)-(E)-3-n -Bu t yl-2-(p -t olylsu lfon yl)oxi-
r a n e, 6c, (+)-(2R,3R,SS)-3-n -Bu tyl-2-(p-tolylsu lfin yl)oxi-
r a n e, 7c, a n d (+)-(2S,3S,SS)-3-n -Bu t yl-2-(p -t olylsu lfin -
yl)oxir a n e, 8c. From t-BuOOH (85 µL, 61 mg, 0.68 mmol)
in 4 mL of THF with n-BuLi (1.48 M, 0.57 mL, 0.85 mmol)
and a solution of (+)-(R)-(E)-1-hexenyl p-tolyl sulfoxide, 5c,
(37 mg, 0.17 mmol) in 1 mL of THF, according to the general
procedure (4 h), a 25:58:17 mixture of epoxy sulfone 6c and
epoxy sulfoxides 7c and 8c was obtained. Purification by
chromatography (5-20% EtOAc-hexane) afforded 7 mg (18%)
of 6c, 5 mg (12%) of 8c, and 16 mg (40%) of 7c as colorless
oils.
From NaH (11.5 mg, 0.48 mmol) in 3 mL of THF, with
t-BuOOH (60 µL, 43 mg, 0.48 mmol) and a solution of (+)-(R)-
(E)-1-hexenyl p-tolyl sulfoxide, 5c, (27 mg, 0.12 mmol) in 1
mL of THF, according to the general procedure (1 h 30 min),
a 13:83:4 mixture of epoxy sulfone 6c and epoxy sulfoxides 7c
and 8c was obtained. Purification by chromatography (5-20%
EtOAc-hexane) afforded 3 mg (10%) of 6c, 18 mg (62%) of
7c, and 1 mg (3%) of 8c as colorless oils.
Gen er a l P r oced u r e for th e Syn th esis of 2-(p-Tolyl-
su lfin yl)-1,3-bu ta d ien es a n d 1-P h en yl-1-h exen yl p-Tolyl
Su lfoxid es.6b To a solution of 1 equiv of an R-iodovinyl
sulfoxide in anhydrous THF (10 mL/mmol), at room temper-
ature and under an atmosphere of argon, was added 20%
Ph3As followed by 1 equiv of 2,6-di-tert-butyl-4-methylphenol
(BHT) and 1.1 equiv of the corresponding vinyl stannane.
Argon was bubbled through the reaction mixture for 10 min,
and 5% Pd2(dba)3‚CHCl3 was then added. The resulting
mixture was refluxed (silicone bath at 70 °C) for 31c or stirred
at room temperature for 35b, until disappearance of starting
material by TLC, approximately 2 h. In the case of 18, the
above conditions were not appropriate; adequate results were
obtained by using DMF and PdCl2(CH3CN)2 in a very slow
coupling. The reaction mixture was quenched with a saturated
solution of KF (3 mL/mmol) and diluted with EtOAc (10 mL/
mmol), and the layers were separated. The aqueous layer was
extracted with EtOAc (three times, 10 mL/mmol), and the
combined organic layers were washed with a saturated solu-
tion of NaCl (3 mL/mmol) and dried over anhydrous MgSO4.
Removal of the drying agent by filtration and concentration
under reduced pressure gave a crude product which was
purified by column chromatography on silica gel using gradient
elution with EtOAc-hexane mixtures. Complete removal of
traces of n-Bu3SnI frequently required a second chromatog-
raphy.
Syn th esis of (-)-(S)-(Z)-1-P h en yl-1-h exen yl p-Tolyl
Su lfoxid e, 18. From (-)-(S)-(1E)-1-iodo-1-(p-tolylsulfinyl)-1-
hexene (95 mg, 0.27 mmol) in 2.7 mL of DMF, Ph3As (15.3
mg, 0.05 mmol), BHT (60.1 mg, 0.27 mmol), Bu3SnPh (0.16
mL, 180 mg, 0.49 mmol), and PdCl2(CH3CN)2 (5.60 mg, 0.022
mmol), according to the general procedure (216 h), an 80:20
mixture of vinyl sulfoxides 18 and 9c was obtained. Purifica-
tion by chromatography (50% CH2Cl2-hexane-2% EtOAc-
CH2Cl2) afforded 39 mg of 18 (40%) as a colorless oil. Data of
18: Rf ) 0.26 (15% EtOAc-hexane). [R]20D ) -47.5 (c ) 0.55).
1H NMR (300 MHz) δ 0.97 (t, 3 H J ) 7.0 Hz), 1.52 (m, 4 H),
2.31 (s, 3 H), 2.67 (m, 1 H), 2.84 (m, 1 H), 6.16 (dd, 1 H, J )
8.4, 7.2 Hz), 7.01-7.27 (m, 9 H). 13C NMR (50 MHz) δ 13.9,
21.3, 22.4, 28.5, 31.7, 124.4 (2 C), 127.6 (2 C), 128.0 (2 C), 129.4
(2 C), 134.2, 139.0, 140.4, 141.6, 145.3.
Syn t h esis of (-)-(R)-(1Z,3E)-1-n -Bu t yl-4-(h yd r oxy-
m eth yl)-2-(p-tolylsu lfin yl)-1,3-bu ta d ien e, 35b. From (-)-
(S)-(1E)-1-iodo-1-(p-tolylsulfinyl)-1-hexene (372 mg, 1.07 mmol)
in 7 mL of THF, with BHT (236 mg, 1.07 mmol), Ph3As (66
mg, 0.21 mmol), (2E)-3-(tributylstannyl)propen-1-ol (446 mg,
1.23 mmol) in 3 mL of THF, and Pd2(dba)3‚CHCl3 (55 mg, 0.05
mmol), according to the general procedure and after purifica-
tion by chromatography (10-100% EtOAc-hexane), diene 35b
(238 mg, 80%) was obtained as a colorless oil. Data of 35b:
Rf ) 0.16 (75% EtOAc-hexane). [R]20 ) -162.1 (c ) 1.55).
From KH (8 mg, 0.20 mmol) in 1.25 mL of THF, with
t-BuOOH (25 µL, 18 mg, 0.25 mmol) and a solution of (+)-(R)-
(E)-1-hexenyl p-tolyl sulfoxide, 5c, (22 mg, 0.10 mmol) in 0.70
mL of THF, according to the general procedure (9 min), a 94:6
mixture of epoxy sulfoxides 7c and 8c was obtained. Purifica-
tion by chromatography (5-20% EtOAc-hexane) afforded 1
mg (4%) of 8c and 14.5 mg (61%) of 7c as colorless oils. Data
D
1H NMR (300 MHz) δ 0.94 (t, 3 H, J ) 7.1 Hz), 1.37-1.55 (m,
4 H), 1.61 (br s, 1 H), 2.37 (s, 3 H), 2.51 (m, 1 H), 2.70 (m, 1
H), 4.07 (t, 2 H, J ) 5.2 Hz), 6.06 (d, 1 H, J ) 16.0 Hz), 6.15
(dt, 1 H, J ) 15.7, 4.8 Hz), 6.24 (t, 1 H, J ) 7.9 Hz), 7.26 (d,
2 H, J ) 8.2 Hz), 7.40 (d, 2 H, J ) 8.2 Hz). 13C NMR (50 MHz)
δ 13.9, 21.3, 22.3, 28.6, 31.6, 63.1, 121.6, 124.3 (2 C), 129.8 (2
C), 133.7, 138.6, 139.7, 140.7, 142.2.
of 6c: Rf ) 0.30 (20% EtOAc-hexane). [R]20 ) +49.3 (c )
D
1.00). 1H NMR (300 MHz) δ 0.88 (t, 3 H, J ) 7.1 Hz), 1.33-
1.44 (m, 4 H), 1.59-1.70 (m, 2 H), 2.44 (s, 3 H), 3.59 (ddd, 1
H, J ) 6.5, 4.9, 1.7 Hz), 3.85 (d, 1 H, J ) 1.7 Hz), 7.36 (d, 2 H,
J ) 8.0 Hz), 7.78 (d, 2 H, J ) 8.3 Hz). 13C NMR (50 MHz) δ
13.8, 21.7, 22.1, 27.5, 30.0, 58.0, 68.4, 128.7 (2 C), 130.0 (2 C),
134.0, 145.5. Data of 8c: Rf ) 0.33 (30% EtOAc-hexane).
Gen er a l P r oced u r e for Nu cleop h ilic Ep oxid a tion of
Vin yl Su lfoxid es. (a ) Wit h LiOO-t-Bu . A two-necked
(33) Prepared from commercially available phenyl vinyl sulfoxide
by the following sequence: 1. LDA, THF, -78 °C. 2. EtCHO. 3. MsCl,
Et3N, THF. 4. n-BuCuCNLi, THF. Unpublished results from our
laboratories. For related transformations, see ref 6d.
(34) Truce, W. E.; Lusch, M. J . J . Org. Chem. 1978, 43, 2252-2258.
See also ref 29.
(35) Prepared from cyclohexanone and thiophenol and subsequent
oxidation with m-CPBA. See: Labiad, B.; Villemin, D. Synthesis 1989,
143-144.
(36) Yechezkel, T.; Ghera, E.; Ostercamp, D.; Hassner, A. J . Org.
Chem. 1995, 60, 5135-5142. For the preparation of related enan-
tiopure keto vinyl sulfoxides, see: Hulce, M.; Mallamo, J . P.; Frye, L.
L.; Kogan, T. P.; Posner, G. H. Organic Syntheses; Wiley: New York,
1990; Coll. Vol. VII, pp 495-500.
[R]20 ) +113.3 (c ) 0.70). 1H NMR (300 MHz) δ 0.84 (t, 3 H,
D
J ) 7.1 Hz), 1.23-1.39 (m, 4 H), 1.56-1.63 (m, 2 H), 2.41 (s,
3 H), 3.58 (td, 1 H, J ) 5.7, 1.8 Hz), 3.66 (d, 1 H, J ) 1.9 Hz),
7.34 (d, 2 H, J ) 8.0 Hz), 7.54 (d, 2 H, J ) 8.3 Hz). 13C NMR
(50 MHz) δ 13.8, 21.5, 22.2, 27.7, 30.3, 56.2, 72.8, 124.4 (2 C),
130.1 (2 C), 137.7, 142.3. Data of 7c: Rf ) 0.28 (30% EtOAc-
hexane). [R]20 ) +195.6 (c ) 1.10). 1H NMR (300 MHz) δ
D
0.85 (t, 3 H, J ) 7.1 Hz), 1.23-1.40 (m, 4 H), 1.57-1.64 (m, 2
H), 2.40 (s, 3 H), 3.36 (td, 1 H, J ) 5.7, 1.9 Hz), 3.76 (d, 1 H,

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4963
J ) 1.9 Hz), 7.33 (d, 2 H, J ) 8.0 Hz), 7.53 (d, 2 H, J ) 8.3
Hz). 13C NMR (50 MHz) δ 13.8, 21.5, 22.2, 27.7, 30.3, 56.7,
72.7, 124.7 (2 C), 130.1 (2 C), 137.1, 142.3.
(dd, 1 H, J ) 3.8, 0.6 Hz), 7.35 (d, 2 H, J ) 8.5 Hz), 7.63 (d, 2
H, J ) 8.2 Hz). 13C NMR (50 MHz) δ 21.5, 27.7, 32.1, 68.1,
78.6, 125.1 (2 C), 130.3 (2 C), 139.1, 142.8. Partial data of
12e: Rf ) 0.34 (5% CH2Cl2-EtOAc). 1H NMR (300 MHz) δ
2.38 (s, 3 H), 2.85 (dd, 1 H, J ) 3.7, 0.5 Hz), 3.70 (dd, 1H, J )
3.8, 0.5 Hz).
Syn t h esis of (E)-3-(2-P h en ylet h yl)-2-(p -t olylsu lfon -
yl)oxir a n e, 6d , (+)-(2R,3R,SS )-3-(2-P h en ylet h yl)-2-(p -
tolylsu lfin yl)oxir an e, 7d, an d (2S,3S,SS)-3-(2-P h en yleth yl)-
2-(p-tolylsu lfin yl)oxir a n e, 8d . From NaH (29 mg, 1.20
mmol) in 7 mL of THF, with t-BuOOH (0.15 mL, 108 mg, 1.50
mmol) and a solution of (R)-(E)-4-phenyl-1-butenyl p-tolyl
sulfoxide 5d (83 mg, 0.30 mmol) in 2 mL of THF, according to
the general procedure (220 min), a 2:97:1 mixture of epoxy
sulfone 6d epoxy sulfoxide 7d and vinyl sulfoxide 5d was
obtained. Purification by chromatography (50% CH2Cl2-
hexane-60% EtOAc-CH2Cl2) afforded 57 mg of 7d (67%) as
a white solid. Partial data of 6d : Rf ) 0.38 (5% CH2Cl2-
EtOAc). 1H NMR (200 MHz) δ 3.63 (td, 1 H), 3.86 (d, 1 H, J
) 2.1 Hz), 7.80 (d, 2 H, J ) 8.0 Hz). Data of 7d : mp: 93-96
Syn th esis of (()-(2R,3S,SS)-3-n -Bu tyl-2-(ter t-bu tylsu lfi-
n yl)oxir a n e, 11f, a n d (()-(2S,3R,SS)-3-n -Bu tyl-2-(ter t-bu -
tylsu lfin yl)oxir a n e, 12f. From t-BuOOH (75 µL, 54 mg, 0.60
mmol) in 1.5 mL of THF, with n-BuLi (1.61 M, 0.47 mL, 0.75
mmol) and a solution of (()-(Z)-1-hexenyl tert-butyl sulfoxide
(29 mg, 0.15 mmol) in 1.5 mL of THF, according to the general
procedure (3 h 30 min), a 98:2 mixture of epoxy sulfoxides 11f
and 12f was obtained. Purification by chromatography (50%
CH2Cl2-hexane: 10% EtOAc-CH2Cl2) afforded 24 mg (79%)
of 11f as a colorless oil. Data of 11f: Rf ) 0.39 (20% EtOAc-
CH2Cl2). 1H NMR (300 MHz) δ 0.89 (t, 3 H, J ) 7.2 Hz), 1.31
(s, 9 H), 1.32-1.60 (m, 4 H), 1.70-1.82 (m, 2 H), 3.22 (td, 1 H,
J ) 8.0, 4.0 Hz), 3.84 (d, 1 H, J ) 3.8 Hz). 13C NMR (50 MHz)
δ 13.8, 22.3, 23.2 (3 C), 28.2, 28.9, 54.8, 58.3, 66.3. Partial
data of 12f: Rf ) 0.40 (20% EtOAc-CH2Cl2). 1H NMR (300
MHz) δ 0.92 (t, 3 H, J ) 7.0 Hz), 1.46 (s, 9 H), 3.23 (ddd, 1 H,
J ) 10.3, 6.1, 4.2 Hz), 4.07 (d, 1 H, J ) 4.1 Hz).
°C (5% EtOAc-hexane). Rf ) 0.22 (5% CH2Cl2-EtOAc). [R]20
D
) +189.7 (c ) 1.17). 1H NMR (300 MHz) δ 1.92-1.99 (m, 2
H), 2.42 (s, 3 H), 2.74 (m, 2 H), 3.45 (td, 1 H, J ) 5.7, 1.8 Hz),
3.73 (d, 1 H, J ) 2.0 Hz), 7.14-7.36 (m, 7 H), 7.53 (d, 2 H, J
) 8.2 Hz). 13C NMR (50 MHz) δ 21.4, 31.7, 32.4, 56.1, 72.7,
124.8, 126.3, 128.3, 128.6, 130.1, 137.0, 140.3, 142.3.
Syn t h esis of (Z)-3-P h en yl-2-(p-t olylsu lfon yl)oxir a n e,
10a , (-)-(2R,3S,SS)-3-P h en yl-2-(p-t olylsu lfin yl)oxir a n e,
11a , a n d (-)-(2R,3R,SS)-3-P h en yl-2-(p -t olylsu lfin yl)oxi-
r a n e, 7a . From t-BuOOH (0.20 mL, 144 mg, 1.6 mmol) in 4
mL of THF, with n-BuLi (1.27 M, 1.57 mL, 2.0 mmol) and a
solution of (-)-(R)-(Z)-2-phenyl-1-p-tolylsulfinyl ethylene, 9a ,
(97 mg, 0.40 mmol) in 4 mL of THF, according to the general
procedure (4 h), a 6:86:8 mixture of epoxy sulfone 10a and
epoxy sulfoxides 11a and 7a was obtained. Purification by
chromatography (5-40% EtOAc-hexane) and recrystallization
(20% EtOAc-hexane) afforded 4 mg (4%) of 10a , 73 mg (71%)
of 11a , and 9 mg (9%) of 7a as white solids.
Syn th esis of (Z)-3′-[[(ter t-Bu tyld ip h en ylsilyl)oxy]p r o-
p yl]-1-(p -t olylsu lfon yl)oxir a n e, 10g, (-)-(2R,3S,SS)-3′-
[[(ter t-Bu tyld ip h en ylsilyl)oxy]p r op yl]-1-(p-tolylsu lfin yl)-
oxir an e, 11g, an d (2S,3R,SS)-3′-[[(ter t-Bu tyldiph en ylsilyl)-
oxy]p r op yl]-1-(p-tolylsu lfin yl)oxir a n e, 12g. From NaH
(22.3 mg, 0.93 mmol) in 5 mL of THF, with t-BuOOH (0.11
mL, 83 mg, 0.92 mmol) and a solution of (-)-(Z)-(S)-5-[(tert-
butyldiphenylsilyl)oxy]-1-pentenyl p-tolyl sulfoxide (100 mg,
0.23 mmol) in 2 mL of THF, according to the general procedure
(25 min), a 1:92:2:5 mixture of epoxy sulfone 10g, epoxy
sulfoxides 11g and 12g, and the corresponding allyl sulfoxide
was obtained. Purification by chromatography (5-30% EtOAc-
hexane) afforded 77 mg of 11g (77%) as a colorless oil. Data
From NaH (94 mg, 3.9 mmol) in 20 mL of THF, with
t-BuOOH (0.49 mL, 353 mg, 3.92 mmol) and a solution of (-)-
(R)-(Z)-2-phenyl-1-p-tolylsulfinyl ethylene, 9a , (237 mg, 0.98
mmol) in 7 mL of THF, according to the general procedure
(30 min), a 3:96:1 mixture of epoxy sulfone 10a and epoxy
sulfoxides 11a and 7a was obtained. Recrystallization (20%
EtOAc-hexane) afforded 200 mg of 11a (79%), and purification
by chromatography of the mother liquors (10-30% EtOAc-
hexane) afforded 25 mg of 11a (10%) as a white solid. Data
of 10a : Rf ) 0.42 (30% EtOAc-hexane). 1H NMR (300 MHz)
δ 2.40 (s, 3 H), 4.28 (d, 1 H, J ) 3.9 Hz), 4.34 (d, 1 H, J ) 3.8
Hz), 7.20 (d, 2 H, J ) 8.2 Hz), 7.29-7.32 (m, 5 H), 7.47 (d, 2
H, J ) 8.3 Hz). Data of 11a : mp: 130-132 °C (20% EtOAc-
of 11g: Rf ) 0.33 (5% EtOAc-hexane). [R]20 ) -3.2 (c )
D
1.79). 1H NMR (300 MHz) δ 1.05 (s, 9 H), 1.72-2.08 (m, 4 H),
2.42 (s, 3 H), 3.14 (ddd, 1 H, J ) 7.9, 4.3, 3.7 Hz), 3.74 (m, 2
H), 3.90 (dd, 1 H, J ) 3.8, 0.8 Hz), 7.31-7.54 (m, 8 H), 7.56 (d,
2 H, J ) 8.2 Hz), 7.66 (m, 4 H). 13C NMR (75 MHz) δ 19.2,
21.9, 25.9, 26.9, 29.6, 58.3, 62.9, 75.7, 124.5, 127.7, 129.7, 130.3,
133.6, 133.7, 135.5 (2 C), 138.1, 142.1. Partial data of 12g: Rf
) 0.23 (30% EtOAc-hexane). 1H NMR (300 MHz) δ 2.37 (s,
3 H), 3.46 (m, 1 H), 3.89 (d, 1 H, J ) 3.8 Hz).
Syn t h esis of (+)-(2S,3S,SS)-3-n -Bu t yl-2-p h en yl-2-(p -
tolylsu lfin yl)oxir a n e, 19, a n d (2R,3R,SS)-3-n -Bu tyl-2-(p-
tolylsu lfin yl)oxir a n e, 20. From NaH (3 mg, 0.12 mmol) in
0.6 mL of THF, with t-BuOOH (15 µL, 11 mg, 0.12 mmol) and
a solution of (-)-(Z)-(S)-1-phenyl-1-hexenyl p-tolyl sulfoxide
(9 mg, 0.03 mmol) in 0.2 mL of THF, according to the general
procedure (1 h 30 min), a 78:22 mixture of epoxy sulfoxides
19 and 20 was obtained.
hexane). Rf ) 0.24 (30% EtOAc-hexane). [R]20 ) -259.4 (c
D
) 1.24). 1H NMR (300 MHz) δ 2.36 (s, 3 H), 4.17 (d, 1 H, J )
3.7 Hz), 4.20 (d, 1 H, J ) 3.8 Hz), 7.01 (d, 2 H, J ) 8.2 Hz),
7.19 (d, 2 H, J ) 7.9 Hz), 7.37-7.40 (m, 5 H). 13C NMR (50
MHz) δ 21.4, 57.5, 78.4, 124.1 (2 C), 126.6 (2 C), 128.5 (2 C),
129.0, 130.0 (2 C), 132.3, 137.0, 142.3. Data of 7a : mp: 109-
110 °C (20% EtOAc-hexane). Rf ) 0.32 (30% EtOAc-hexane).
From KH (5.3 mg, 0.13 mmol) in 1 mL of THF, with
t-BuOOH (16 µL, 12 mg, 0.13 mmol) and a solution of (-)-(Z)-
(S)-1-phenyl-1-hexenyl p-tolyl sulfoxide (10 mg, 0.033 mmol)
in 0.5 mL of THF, according to the general procedure (3 h, 30
min), a 80:8:12 mixture of epoxy sulfoxides 19 and 20 and vinyl
sulfoxide 18 was obtained. Purification by chromatography
(25% CH2Cl2-hexane: 10% EtOAc-CH2Cl2) afforded 8.5 mg
(81%) of 19 as a white solid, traces of 20, and 1 mg (10%) of
18 as colorless oils. Data of 19: mp: 99-101 °C (20% EtOAc-
[R]20 ) -4.8 (c ) 0.31). 1H NMR (300 MHz) δ 2.42 (s, 3 H),
D
4.70 (s, 2 H), 7.32 (d, 2 H, J ) 7.9 Hz), 7.46 (t, 2 H, J ) 7.6
Hz), 7.60 (t, 1 H, J ) 7.4 Hz), 7.74 (d, 2 H, J ) 8.4 Hz), 7.93
(d, 2 H, J ) 7.2 Hz). 13C NMR (50 MHz) δ 21.7, 63.6, 80.6,
128.6 (2 C), 128.8 (2 C), 129.3 (2 C), 129.8 (2 C), 134.3, 135.8,
145.4, 151.9.
Syn th esis of (Z)-3-ter t-Bu tyl-2-(p-tolylsu lfon yl)oxir an e,
10e, (+)-(2R,3S,SS)-3-ter t-Bu tyl-2-(p-tolylsu lfin yl)oxir a n e,
11e, a n d (2S,3R,SS)-3-ter t-Bu t yl-2-(p -t olylsu lfin yl)oxi-
r a n e, 12e. From NaH (50 mg, 2.10 mmol) in 9 mL of THF,
with t-BuOOH (0.26 mL, 189 mg, 2.10 mmol) and a solution
of (R)-(Z)-3,3-dimethyl-1-butenyl p-tolyl sulfoxide (78 mg, 0.35
mmol) in 2 mL of THF, according to the general procedure (1
day), a 3:85:2:10 mixture of epoxy sulfone 10e, epoxy sulfoxides
11e and 12e, and vinyl sulfoxide 9e was obtained. Purification
by chromatography (50% CH2Cl2-hexane-5% EtOAc-CH2Cl2)
afforded 4 mg of 10e (3%), 50 mg of 11e (70%), and 6 mg of 9e
(8%) as colorless oils. Data of 11e: Rf ) 0.36 (5% CH2Cl2-
hexane). Rf ) 0.15 (10% EtOAc-hexane). [R]20 ) +70.6 (c
D
) 0.69). 1H NMR (300 MHz) δ 1.00 (t, 3 H J ) 7 Hz), 1.48-
1.61 (m, 4 H), 2.18-2.40 (m, 2 H), 2.34 (s, 3 H), 3.23 (t, 1 H,
J ) 6.3 Hz), 6.98 (dd, 2 H, J ) 7.9, 1.4 Hz), 7.11-7.27 (m, 7
H). 13C NMR (50 MHz) δ 14.0, 21.4, 22.4, 27.4, 29.2, 66.8, 80.5,
125.3 (2 C), 127.6 (2 C), 128.4 (2 C), 127.6, 128.4, 128.9, 129.3
(2 C), 131.7, 137.6, 141.9. Partial data of 20: Rf ) 0.18 (10%
EtOAc-hexane). 1H NMR (300 MHz) δ 0.94 (t, 3 H, J ) 7.2
Hz), 1.43-1.65 (m, 4 H), 2.11-2.20 (m, 2 H), 2.29 (s, 3 H),
3.26 (dd, 1 H, J ) 5.9, 6.9 Hz), 6.92 (dd, 2 H, J ) 8.4, 1.2 Hz),
7.07-7.23 (m, 7 H).
EtOAc). [R]20 ) +130.5 (c ) 1.55). 1H NMR (300 MHz) δ
Syn t h esis of (()-(1R,6S,SS)-1-(P h en ylsu lfin yl)-7-oxa -
D
1.06 (s, 9 H), 2.41 (s, 3 H), 3.00 (dd, 1 H, J ) 3.8, 0.5 Hz), 3.98
bicyclo[4.1.01,6]h ep ta n -2-on e, 29b, a n d (()-(1S,6R,SS)-1-

4964 J . Org. Chem., Vol. 63, No. 15, 1998
Ferna´ndez de la Pradilla et al.
(P h en ylsu lfin yl)-7-oxa bicyclo[4.1.01,6]h ep ta n -2-on e, 30b.
From t-BuOOH (85 µL, 61.3 mg, 0.68 mmol) in 5 mL of THF
with n-BuLi (1.4 M, 0.6 mL, 0.85 mmol) and a solution of (()-
2-(phenylsulfinyl)-2-cyclohexenone, 27b, (39 mg, 0.17 mmol)
in 2 mL of THF, according to the general procedure (-78 °C,
10 min), a 9:91 mixture of epoxy sulfoxides 29b and 30b was
obtained. Purification by chromatography (5-30% EtOAc-
hexane) afforded 20 mg (48%) of 30b, as a white solid.
From NaH (9 mg, 0.40 mmol) in 2 mL of THF, with
t-BuOOH (50 µL, 36 mg, 0.40 mmol) and a solution of (()-2-
(phenylsulfinyl)-2-cyclohexenone, 27b, (24 mg, 0.10 mmol) in
1 mL of THF, according to the general procedure (-78 °C, 17
min), a 36:64 mixture of epoxy sulfoxides 29b and 30b was
obtained. Purification by chromatography (1-10% EtOAc-
CH2Cl2) afforded 7 mg (28%) of 30b, and 4 mg (16%) of 29b as
white solids. Data of 30b: mp: 96-99 °C. Rf ) 0.38 (10%
EtOAc-CH2Cl2). 1H NMR (300 MHz) δ 1.54-1.84 (m, 4 H),
2.34-2.52 (m, 2 H), 4.21 (m, 1 H), 7.43-7.51 (m, 3 H), 7.64-
7.70 (m, 2 H). 13C NMR (50 MHz) δ 16.1, 22.8, 38.3, 53.1, 73.6,
126.0 (2 C), 129.3 (2 C), 131.8, 140.4, 201.5. Partial data of
29b: Rf ) 0.31 (10% EtOAc-CH2Cl2). 1H NMR (300 MHz) δ
4.10 (m, 1 H) 7.76-7.80 (m, 5 H). 13C NMR (50 MHz) δ 17.1,
23.0, 37.2, 126.3, 128.7, 131.7.
Syn t h esis of (-)-(E)-3-n -Bu t yl-2-(p -t olylsu lfon yl)-2-
vin yl oxir a n e, 32a , (+)-(2S,3S,SS)-3-n -Bu tyl-2-(p-tolyl-
su lfin yl)-2-vin yl oxir a n e, 33a , a n d (-)-(2R,3R,SS)-3-n -
Bu t yl-2-(p -t olylsu lfin yl)-2-vin yl oxir a n e, 34a . From t-
BuOOH (0.37 mL, 267 mg, 2.96 mmol) in 37 mL of THF, with
n-BuLi (1.58 M, 2.37 mL, 3.75 mmol) and a solution of sulfinyl
diene 31a (184 mg, 0.74 mmol) in 8 mL of THF, according to
the general procedure (2 h), a 20:80 mixture of epoxy sulfoxides
33a and 34a and traces of sulfone 32a was obtained. Purifica-
tion by chromatography (5-20% EtOAc-hexane) afforded 105
mg (59%) of 34a and 28 mg (16%) of 33a as colorless oils.
From NaH (7.7 mg, 0.32 mmol) in 4.2 mL of THF, with
t-BuOOH (40 µL, 29 mg, 0.32 mmol) and a solution of sulfinyl
diene 31a (20 mg, 0.08 mmol) in 1.4 mL of THF, according to
the general procedure (90 min), a 8:84:8 mixture of epoxy
sulfone 32a and epoxy sulfoxides 33a and 34a was obtained.
Purification by chromatography (5-20% EtOAc-hexane) af-
forded 1 mg (4%) of 32a , 11 mg (52%) of 33a , and 1 mg (5%)
of 34a . Data of 32a : From other experiments that produced
substantial amounts of sulfone 32a . The optical purity has
33c: Rf ) 0.23 (20% EtOAc-CH2Cl2). [R]20 ) +173.5 (c )
D
0.22). 1H NMR (300 MHz) δ 0.94 (t, 3 H, J ) 7.1 Hz), 1.23-
1.49 (m, 6 H), 2.37 (s, 3 H), 2.90 (s, 1 H), 3.63 (t, 1 H, J ) 5.9
Hz), 4.09 (m, 2 H), 5.78 (m, 2 H), 7.25 (d, 2 H, J ) 8.4 Hz),
7.46 (d, 2 H, J ) 8.3 Hz). 13C NMR (50 MHz) δ 13.8, 21.4,
22.2, 27.2, 28.0, 61.9, 62.2, 78.9, 116.8, 125.7 (2 C), 129.4 (2
C), 135.7, 139.6, 142.1. Partial data of 34c: Rf ) 0.16 (20%
EtOAc-CH2Cl2). 1H NMR (200 MHz) δ 2.39 (s, 3 H), 3.75 (t,
1 H, J ) 5.9 Hz).
Syn t h esis of (+)-(2R,3S,SS)-3-n -Bu t yl-2-(p-t olylsu lfi-
n yl)-2-vin yloxir a n e, 37a , a n d (-)-(2S,3R,SS)-3-n -Bu tyl-2-
(p-tolylsu lfin yl)-2-vin yloxir a n e, 38a . From t-BuOOH (0.25
mL, 180 mg, 2.00 mmol) in 25 mL of THF, with n-BuLi (1.88
mL, 1.60 M, 2.51 mmol) and a solution of sulfinyl diene 35a
(125 mg, 0.50 mmol) in 5 mL of THF, according to the general
procedure (2 h), a 77:23 mixture of epoxy sulfoxides 37a and
38a was obtained. Purification by chromatography (5-20%
EtOAc-hexane) afforded 25 mg (19%) of 38a and 85 mg (64%)
of 37a as colorless oils.
From NaH (19.2 mg, 0.84 mmol) in 4.2 mL of THF, with
t-BuOOH (100 µL, 72 mg, 0.8 mmol) and a solution of sulfinyl
diene 35a (50 mg, 0.20 mmol) in 1.4 mL of THF, according to
the general procedure (25 min), a 95:5 mixture of epoxy
sulfoxides 37a and 38a was obtained. Purification by chro-
matography (5-30% EtOAc-hexane) afforded 41 mg (77%) of
37a and 2 mg (4%) of 38a as colorless oils. Data of 37a : Rf )
0.18 (20% EtOAc-hexane). [R]20D ) +17.1 (c ) 1.67). 1H NMR
(200 MHz) δ 0.94 (t, 3 H, J ) 7.2 Hz), 1.38-1.69 (m, 4 H),
1.95-2.06 (m, 2 H), 2.39 (s, 3 H), 3.06 (dd, 1 H, J ) 7.0, 6.2
Hz), 5.31 (dd, 1 H, J ) 10.5, 1.5 Hz), 5.35 (dd, 1 H, J ) 17.1,
1.5 Hz), 5.78 (dd, 1 H, J ) 17.1, 10.5 Hz), 7.31 (d, 2 H, J ) 8.6
Hz), 7.49 (d, 2 H, J ) 8.3 Hz). 13C NMR (50 MHz) δ 13.9,
21.4, 22.3, 28.4, 29.1, 67.2, 79.3, 122.0, 124.9, (2 C), 126.8, 129.9
(2 C), 137.7, 141.9. Data of 38a : Rf ) 0.28 (20% EtOAc-
hexane). [R]20D ) -68.0 (c ) 1.20). 1H NMR (200 MHz) δ 0.96
(t, 3 H, J ) 7.2 Hz), 1.44-1.68 (m, 4 H), 1.94-2.24 (m, 2 H),
2.38 (s, 3 H), 3.13 (dd, 1 H, J ) 6.9, 5.6 Hz), 5.10 (dd, 1 H, J
) 17.1, 1.6 Hz), 5.20 (dd, 1 H, J ) 10.9, 1.6 Hz), 6.24 (dd, 1 H,
J ) 17.2, 10.9 Hz), 7.27 (d, 2 H, J ) 8.5 Hz), 7.47 (d, 2 H, J )
8.3 Hz). 13C NMR (50 MHz) δ 13.9, 21.4, 22.4, 28.1, 28.4, 69.2,
75.9, 119.9, 125.0 (2 C), 126.1, 129.4 (2 C), 136.5, 141.5.
Syn th esis of (+)-(2R,3S)-3-n -Bu tyl-2-(p-tolylsu lfon yl)-
2-vin yloxir a n e, 36a . From t-BuOOH (65 µL, 47 mg, 0.52
mmol) in 6.5 mL of Et2O, with n-BuLi (1.6 M, 0.40 mL, 0.65
mmol) and a solution of sulfinyl diene 35a (32.3 mg, 0.13
mmol) in 1.3 mL of Et2O, according to the general procedure
(2 h) after chromatography (5-20% EtOAc-hexane), 33.3 mg
(92%) of epoxy sulfone 36a was obtained as a colorless oil. The
optical purity of this sample of 36a is estimated at 84% ee.
not been determined. Rf ) 0.35 (20% EtOAc-hexane). [R]20
D
) -44.0 (c ) 0.59). 1H NMR (200 MHz) δ 0.88 (t, 3 H, J ) 7.3
Hz), 1.24-1.52 (m, 6 H), 2.42 (s, 3 H), 3.94 (t, 1 H, J ) 5.8
Hz), 5.21 (dd, 1 H, J ) 17.1, 1.5 Hz), 5.43 (dd, 1 H, J ) 10.9,
1.5 Hz), 6.25 (dd, 1 H, J ) 17.1, 10.9 Hz), 7.30 (d, 2 H, J ) 8.6
Hz), 7.70 (d, 2 H, J ) 8.4 Hz). 13C NMR (50 MHz) δ 13.8,
21.7, 22.2, 26.6, 27.9, 63.3, 77.2, 123.9, 125.1, 129.5 (5 C), 145.1.
Data of 33a : White solid. mp: 44-46 °C (Hexane). Rf ) 0.18
Data of 36a : Rf ) 0.43 (30% EtOAc-hexane). [R]20 ) +82.8
D
(c ) 3.30). 1H NMR (200 MHz) δ 0.95 (t, 3 H, J ) 7.0 Hz),
1.35-1.65 (m, 4 H), 2.25-2.45 (m, 2 H), 2.42 (s, 3 H), 3.02 (t,
1 H, J ) 6.3 Hz), 5.14 (dd, 2 H, J ) 17.0, 10.6 Hz), 5.20 (dd,
1 H, J ) 16.9, 1.3 Hz), 6.19 (dd, 1 H, J ) 17.0, 10.6 Hz), 7.32
(d, 2 H, J ) 8.3 Hz,), 7.73 (d, 2 H, J ) 8.3 Hz). 13C NMR (50
MHz) δ 13.8, 21.6, 22.5, 27.0, 29.1, 71.2, 76.4, 119.7, 129.2 (2
C), 129.5 (2 C), 129.8, 145.8.
(20% EtOAc-hexane). [R]20 ) +165.9 (c ) 0.78). 1H NMR
D
(200 MHz) δ 0.87 (t, 3 H, J ) 7.3 Hz), 1.33-1.55 (m, 6 H),
2.38 (s, 3 H), 3.68 (t, 1 H, J ) 6.0 Hz), 5.26 (dd, 1 H, J ) 17.2,
1.4 Hz), 5.44 (dd, 1 H, J ) 10.9, 1.4 Hz), 5.81 (dd, 1 H, J )
17.2, 10.9 Hz), 7.26 (d, 2 H, J ) 8.0 Hz), 7.46 (d, 2 H, J ) 8.2
Hz). 13C NMR (50 MHz) δ 13.9, 21.5, 22.4, 27.2, 28.0, 62.4,
79.0, 123.7, 125.9 (2 C), 126.1, 129.4 (2 C), 135.8, 142.2. Data
Syn th esis of (+)-(E)-(2R,3S,SS)-3-n -Bu tyl-2-(p-tolylsu lfi-
n yl-2-[2′-(h yd r oxym eth yl)vin yl]oxir a n e, 37b. From NaH
(67 mg, 2.8 mmol) in 17.5 mL of THF, with t-BuOOH (0.35
mL, 252 mg, 2.8 mmol) and a solution of sulfinyl diene 35b
(195 mg, 0.7 mmol), in 5 mL of THF, according to the general
procedure (90 min), a 98:2 mixture of epoxy sulfoxide 37b and
epoxy sulfone 36b was obtained. Purification by chromatog-
raphy (10-100% EtOAc-hexane) afforded 194 mg (94%) of
37b as a colorless oil which solidified upon standing. Data of
37b: mp: 66-68 °C (5% EtOAc-hexane). Rf ) 0.23 (75%
of 34a : Rf ) 0.21 (20% EtOAc-hexane). [R]20 ) -57.6 (c )
D
1.24). 1H NMR (200 MHz) δ 0.87 (t, 3 H, J ) 7.3 Hz), 1.29-
1.55 (m, 6 H), 2.39 (s, 3 H), 3.73 (t, 1 H, J ) 5.9 Hz), 5.20 (dd,
1 H, J ) 17.2, 1.7 Hz), 5.39 (dd, 1 H, J ) 11.1, 1.7 Hz), 5.91
(dd, 1 H, J ) 17.2, 11.1 Hz), 7.27 (d, 2 H, J ) 8.0 Hz), 7.48 (d,
2 H, J ) 8.3 Hz). 13C NMR (50 MHz) δ 13.8, 21.5, 22.2, 27.2,
28.0, 63.7, 77.2, 123.4, 123.5, 125.3 (2 C), 129.5 (2 C), 137.1,
142.0.
Syn t h esis of (+)-(E)-(2R,3R,SS)-3-n -Bu t yl-2-(p -t olyl-
su lfin yl)-2-[2′-(h yd r oxym eth yl)vin yl]oxir a n e, 33c. From
NaH (6.9 mg, 0.29 mmol) in 1.8 mL of THF, with t-BuOOH
(36 µL, 26 mg, 0.28 mmol) and a solution of sulfinyl diene 31c
(20 mg, 0.072 mmol) in 0.5 mL of THF, according to the general
procedure (120 min), a 3:97 mixture of epoxy sulfone 32c and
epoxy sulfoxide 33c and trace amounts of epoxy sulfoxide 34c
was obtained. Purification by chromatography (0-40% EtOAc-
CH2Cl2) gave 17 mg (80%) of 33c as a colorless oil. Data of
EtOAc-hexane). [R]20 ) +122.0 (c ) 1.09). 1H NMR (300
D
MHz) δ 0.94 (t, 3 H, J ) 7.1 Hz), 1.40-1.61 (m, 4 H), 1.98 (m,
2 H), 2.30-2.50 (br m, 1 H), 2.39 (s, 3 H), 3.06 (dd, 1 H, J )
7.2, 5.4 Hz), 4.04 (m, 2 H), 5.70 (dt, 1 H, J ) 15.5, 1.7 Hz),
5.93 (dt, 1 H, J ) 15.4, 4.6 Hz), 7.31 (d, 2 H, J ) 8.1 Hz), 7.47
(d, 2 H, J ) 8.2 Hz). 13C NMR (50 MHz) δ 13.9, 21.5, 22.3,
28.6, 29.1, 62.3, 67.3, 79.3, 118.5, 124.8 (2 C), 130.0 (2 C), 137.5,
137.7, 142.1. Partial data of 36b: Rf ) 0.26 (75% EtOAc-

Nucleophilic Epoxidation of Simple Vinyl Sulfoxides
J . Org. Chem., Vol. 63, No. 15, 1998 4965
hexane). 1H NMR (300 MHz) δ 2.38 (s, 3 H), 3.17 (dd, 1 H, J
) 6.9, 5.7 Hz), 4.05 (m, 2 H), 7.76 (d, 2 H, J ) 8.2 Hz).
Syn th esis of (Z)-2-Vin yl-3-n -bu tyl-3-m eth yl-2-(p-tolyl-
su lfon yl)oxir a n e, 36c, (+)-(2S,3S,SS)-2-Vin yl-3-n -bu tyl-3-
m eth yl-2-(p-tolylsu lfin yl)oxir a n e, 37c, a n d (2R,3R,SS)-2-
Vin yl-3-n -bu tyl-3-m eth yl-2-(p-tolylsu lfin yl)oxir a n e, 38c.
From t-BuOOH (23 µL, 17 mg, 0.18 mmol) in 2 mL of THF
with n-BuLi (1.58 M, 0.14 mL, 0.23 mmol) and a solution of
(Z)-1-n-butyl-1-methyl-2-(p-tolylsulfinyl)-1,3-butadiene (12 mg,
0.046 mmol) in 0.5 mL of THF, according to the general
procedure (24 h), a 12:58:28 mixture of sulfone 36c and
sulfoxides 37c and 38c, along with other uncharacterized
byproducts.
was obtained (10 mg, 95%) as a white solid. Data of 32b:
mp: 81-83 °C (10% ether-hexane). Rf ) 0.41 (20% EtOAc-
hexane). [R]20 ) -104.5 (c ) 0.95). 1H NMR (300 MHz) δ
D
0.86 (t, 3 H, J ) 7.1 Hz), 1.31-1.53 (m, 6 H), 2.39 (s, 3 H,),
4.02 (t, 1 H, J ) 5.9 Hz), 6.41 (d, 1 H, J ) 16.0 Hz), 6.57 (d, 1
H, J ) 16.0 Hz), 7.25-7.32 (m, 7 H), 7.70 (d, 2 H, J ) 8.3 Hz).
13C NMR (50 MHz) δ 13.9, 21.7, 22.2, 26.9, 28.0, 64.0, 76.6,
115.4, 126.9 (2 C), 128.7 (2 C), 128.9, 129.4 (2 C), 129.5 (2 C),
133.0, 135.1, 137.9, 145.1.
Syn th esis of (+)-(2R,3S)-3-n -Bu tyl-2-(p-tolylsu lfon yl)-
2-vin yloxir a n e, 36a . A 25 mL round-bottomed flask was
charged with epoxy sulfoxide 37a (10 mg, 0.038 mmol) in 0.4
mL of MeOH, and the reaction mixture was cooled at 0 °C.
Oxone (70 mg, 0.11 mmol) in 0.4 mL of H2O was then added,
and the resulting mixture was stirred at room temperature
for 6 h. The reaction was then quenched with a saturated
solution of NH4Cl (0.5 mL) and diluted with EtOAc (4 mL),
the layers were separated, and the organic layer was washed
with a saturated solution of NaCl (1 mL). The combined
aqueous layer was extracted with EtOAc (three times, 3 mL).
The combined organic extracts were dried over anhydrous
MgSO4, filtered, and concentrated under reduced pressure to
give a crude product which was purified by chromatography
on silica gel (15-30% EtOAc-hexane) to give enantiomerically
From NaH (9.6 mg, 0.40 mmol) in 2 mL of THF, with
t-BuOOH (50 µL, 36 mg, 0.40 mmol) and a solution of (Z)-1-
n-butyl-1-methyl-2-(p-tolylsulfinyl)-1,3-butadiene (26 mg, 0.10
mmol) in 0.7 mL of THF, according to the general procedure
(2 h 40 min), a 3:92:5 mixture of epoxy sulfone 36c and epoxy
sulfoxides 37c and 38c was obtained. Purification by chro-
matography (5-20% EtOAc-hexane) afforded 17 mg (60%) of
37c as a colorless oil. Data of 36c: Rf ) 0.48 (20% EtOAc-
hexane). 1H NMR (300 MHz) δ 0.95 (t, 3 H, J ) 7.2 Hz), 1.26
(s, 3 H), 1.37-1.65 (m, 4 H), 2.24-2.43 (m, 2 H), 2.41 (s, 3 H),
5.10 (dd, 1 H, J ) 17.0, 1.5 Hz), 5.24 (dd, 1 H, J ) 11.0, 1.4
Hz), 6.04 (dd, 1 H, J ) 17.0, 11.0 Hz), 7.28 (d, 2 H, J ) 8.5
Hz), 7.69 (d, 2 H, J ) 8.4 Hz). 13C NMR (50 MHz) δ 13.9,
20.2, 21.6, 22.8, 28.2, 32.5, 72.5, 81.6, 122.8, 128.9, 129.2 (2
C), 129.3 (2 C), 136.5, 144.7. Data of 37c: Rf ) 0.21 (20%
pure epoxy sulfone 36a (5.9 mg, 68%). ([R]20 ) +99.5 (c )
D
0.59).
Syn t h esis of (-)-(3R,4R,RS)-3-Ch lor o-4-h yd r oxy-3-(p-
tolylsu lfin yl)octa n e, 41, a n d (-)-(3R,4S,RS)-3-Ch lor o-4-
h yd r oxy-3-(p-tolylsu lfin yl)octa n e, 42. A 100 mL round-
bottomed flask was charged with 24 mL of THF and i-Pr2NH
(0.40 mL, 291 mg, 2.88 mmol) and cooled to 0 °C. To the above
solution was added n-BuLi (1.85 mL, 1.42 M, 2.63 mmol), and
the resulting LDA solution (ca. 0.1 M) was stirred at 0 °C for
15 min and then cooled to -78 °C. After 10 min, a solution of
1 equiv of chloro sulfoxide 40 (500 mg, 2.40 mmol) in 12 mL
of THF, previously dried over 4 Å sieves, was added dropwise
to produce a pale orange solution. After stirring for 10 min
at -78 °C, 1.1 equiv of n-pentanal (0.30 mL, 226 mg, 2.63
mmol) was added dropwise, and the resulting colorless solution
was stirred at -78 °C for 10 min. The reaction mixture was
quenched with a saturated solution of NH4Cl (10 mL) and
diluted with EtOAc (24 mL), the layers were separated, and
the organic layer was washed with a saturated solution of
NaCl (12 mL). The aqueous layer was extracted with EtOAc
(three times, 20 mL), and the combined organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure to give a 54:46 mixture of chlorohydrins 41
and 42 which was purified by column chromatography on silica
gel (15-30% EtOAc-hexane) affording 266 mg (38%) of 41 as
a white solid, 313 mg (45%) of 42 as a colorless oil and 22.8
mg of 40. Data of 41: mp: 71-72 °C (Hexane). Rf ) 0.40
EtOAc-hexane). [R]20 ) +129.9 (c ) 0.27). 1H NMR (300
D
MHz) δ 0.96 (t, 3 H, J ) 7.2 Hz), 1.22 (s, 3 H), 1.39-1.64 (m,
4 H), 1.94-2.17 (m, 2 H), 2.40 (s, 3 H), 5.36-5.54 (m, 3 H),
7.31 (d, 2 H, J ) 8.0 Hz), 7.48 (d, 2 H, J ) 8.3 Hz). 13C NMR
(50 MHz) δ 14.0, 18.3, 21.4, 22.8, 27.5, 33.7, 69.6, 85.2, 124.3,
124.8 (2 C), 128.9, 129.8 (2 C), 135.4, 141.6. Partial data of
38c: 1H NMR (200 MHz) δ 0.96 (t, 3 H, J ) 7.1 Hz), 1.27 (s,
3 H), 1.35-1.80 (m, 4 H), 2.05-2.20 (m, 2 H), 2.37 (s, 3 H),
4.93 (dd, 1 H, J ) 17.0, 1.8 Hz), 5.35 (dd, 1 H, J ) 11.0, 1.8
Hz), 6.13 (dd, 1 H, J ) 17.0, 11.0 Hz), 7.24 (d, 2 H, J ) 8.1
Hz), 7.43 (d, 2 H, J ) 8.2 Hz).
Gen er a l P r oced u r e for Oxid a tion of Ep oxy Su lfoxid es
to Ep oxy Su lfon es. A round-bottomed flask was charged
with methanol (ca. 5 mL/mmol), 1 equiv of epoxy sulfoxide,
and 3 equiv of MMPP (80%). The mixture was stirred at room
temperature until starting material disappearance, monitoring
by TLC (7-48 h). The reaction was concentrated under
reduced pressure to remove methanol, quenched with 5%
aqueous NaHCO3 (4 mL/mmol), and diluted with EtOAc (8 mL/
mmol), the layers were separated, and the aqueous layer was
extracted with EtOAc (three times). The combined organic
extracts were washed with a saturated solution of NaCl (4 mL/
mmol), dried over anhydrous MgSO4, filtered, and concentrated
under reduced pressure to give a crude product, which was
purified by column chromatography on silica gel using the
appropriate mixture of EtOAc-hexane.
Syn th esis of (+)-(2R,3S)-3′-[(ter t-Bu tyld ip h en ylsilyl)-
oxy]-1-(p-tolylsu lfon yl)oxir a n e, 10g. From epoxy sulfoxide
11g (13 mg, 0.025 mmol) in 1 mL of methanol and MMPP (46
mg, 0.075 mmol), according to the general procedure (24 h),
an 80:20 mixture of epoxy sulfone 10g and epoxy sulfoxide 11g
was obtained. Purification by chromatography (5-40% EtOAc-
hexane) afforded 2 mg of epoxy sulfoxide 11g and 8 mg of 10g
(70%) as a colorless oil. Data of 10g: Rf ) 0.70 (5% CH2Cl2-
EtOAc). [R]20D ) +37.8 (c ) 0.87). 1H NMR (300 MHz) δ 1.04
(s, 9 H), 1.82 (quint, 2 H, J ) 6.3 Hz), 2.20-2.31 (m, 2 H),
2.44 (s, 3 H), 3.28 (ddd, 1 H, J ) 7.3, 5.5, 3.9 Hz), 3.74 (t, 2 H,
J ) 6.2 Hz), 3.90 (dd, 1 H, J ) 3.9, 0.5 Hz), 7.33-7.41 (m, 8
H), 7.63-7.80 (m, 4 H), 7.82 (d, 2 H, J ) 8.1 Hz). 13C NMR
(50 MHz) δ 19.2, 21.6, 23.6, 26.9, 29.7, 61.1, 63.2, 68.9, 127.6
(2 C), 128.3 (2 C), 129.6 (2 C), 130.0 (2 C), 133.8, 135.6 (2 C),
145.4 (2 C).
(30% EtOAc-hexane). [R]20 ) -113.6 (c ) 5.15). 1H NMR
D
(200 MHz) δ 0.82 (t, 3 H, J ) 7.3 Hz), 1.33 (t, 3 H, J ) 7.0
Hz), 1.18-1.60 (m, 6 H), 2.39 (dq, 1 H, J ) 15.4, 7.7 Hz), 2.44
(s, 3 H), 2.76 (dq, 1 H, J ) 15.4, 7.2 Hz), 3.82 (d, 1 H, J ) 6.9
Hz), 4.85 (br s, 1 H), 7.35 (d, 2 H, J ) 8.3 Hz), 7.68 (d, 2 H, J
) 8.0 Hz). 13C NMR (50 MHz) δ 8.3, 13.9, 21.5, 22.4, 24.1,
28.1, 31.7, 76.0, 85.1, 12.7 (2 C), 129.4 (2 C), 133.0, 143.1. Data
of 42: Rf ) 0.32 (30% EtOAc-hexane). [R]20 ) -84.4 (c )
D
4.10). 1H NMR (200 MHz) δ 0.88 (t, 3 H, J ) 6.8 Hz), 1.15 (t,
3 H, J ) 7.4 Hz), 1.22-1.58 (m, 6 H), 2.02-2.12 (m, 2 H), 2.41
(s, 3 H), 2.59 (m, 1 H), 3.77 (ddd, 1 H, J ) 10.0, 4.5, 1.9 Hz),
7.30 (d, 2 H, J ) 8.3 Hz), 7.63 (d, 2 H, J ) 8.0 Hz). 13C NMR
(50 MHz) δ 9.0, 13.9, 21.3, 22.4, 25.4, 28.4, 31.7, 74.5, 93.8,
126.9 (2 C), 129.2 (2 C), 134.8, 142.5.
Gen er a l P r oced u r e for th e Syn th esis of Su lfin yl Oxi-
r a n es fr om Su lfin yl Ch lor oh yd r in s. A 25 mL round-
bottomed flask was charged with a solution of the chlorohydrin
in THF (ca. 0.1 M), and the solution was cooled to 0 °C.
A
suspension of 2.5 equiv of t-BuOK in THF was then added,
and the resulting yellow solution was stirred for 2 h, after
which time it was quenched with a saturated solution of NH4-
Cl (4 mL/mmol) and diluted with EtOAc (8 mL/mmol), the
layers were separated, and the organic layer was washed with
a saturated solution of NaCl (4 mL/mmol). The combined
Syn th esis of (-)-(2R,3R)-3-n -Bu tyl-2-(p-tolylsu lfon yl)-
2-(2′-p h en ylvin yl)oxir a n e, 32b. From epoxy sulfoxide 33b
(10 mg, 0.03 mmol) in 0.3 mL of MeOH with MMPP (56 mg,
0.09 mmol), according to the general procedure and after
purification by chromatography (5-20% EtOAc-hexane), 32b

4966 J . Org. Chem., Vol. 63, No. 15, 1998
Ferna´ndez de la Pradilla et al.
aqueous layers were extracted with EtOAc (three times, 10
mL/mmol), and the combined organic extracts were dried over
anhydrous MgSO4, filtered, and concentrated under reduced
pressure to give a crude product which was purified by column
chromatography on silica gel (10-30% EtOAc-hexane).
Syn th esis of (-)-(2R,3R,RS)-3-n -Bu tyl-2-eth yl-2-(p-tolyl-
su lfin yl)oxir a n e, 44. From chlorohydrin 42 (220 mg, 0.66
mmol) in 6.6 mL of THF, with t-BuOK (185 mg, 1.65 mmol),
according to the general procedure, epoxide 44 (143 mg, 81%)
was obtained as a colorless oil. Data of 44: Rf ) 0.35 (30%
Syn th esis of (+)-(2S,3S,SS)-3-n -Bu tyl-2-eth yl-2-(p-tolyl-
su lfin yl)oxir a n e, en t-44. From vinyl sulfinyl epoxide 34a
(30 mg, 0.11 mmol) in 1 mL of DME, with TsNHNH2 (151.9
mg, 0.81 mmol) and NaOAc (86.5 mg, 1.08 mmol) in 0.5 mL of
H2O, according to the general procedure, epoxide ent-44 (19.6
mg, 63%) was obtained as a colorless oil. Data of ent-44: Rf )
0.35 (30% EtOAc-hexane). [R]20D ) +52.1 (c ) 1.26). 1H NMR
(200 MHz) δ 0.83 (t, 3 H, J ) 7.6 Hz), 0.87 (t, 3 H, J ) 7.0
Hz), 1.25-1.65 (m, 7 H), 1.81 (m, 1 H), 2.40 (s, 3 H), 3.62 (t, 1
H, J ) 6.2 Hz), 7.27 (d, 2 H, J ) 8.0 Hz), 7.42 (d, 2 H, J ) 8.3
Hz). 13C NMR (50 MHz) δ 9.3, 13.8, 17.4, 21.4, 22.3, 27.7, 28.4,
60.5, 77.6, 125.4 (2 C), 129.8 (2 C), 137.5, 142.1.
EtOAc-hexane). [R]20 ) -53.6 (c ) 2.02). 1H NMR (300
D
MHz) δ 0.83 (t, 3 H, J ) 7.7 Hz), 0.88 (t, 3 H, J ) 7.1 Hz),
1.25-1.65 (m, 7 H), 1.81 (m, 1 H), 2.40 (s, 3 H), 3.62 (t, 1 H,
J ) 6.2 Hz), 7.27 (d, 2 H, J ) 8.0 Hz), 7.42 (d, 2 H, J ) 8.2
Hz,). 13C NMR (50 MHz) δ 9.2, 13.7, 17.3, 21.2, 22.1, 27.5,
28.2, 60.1, 77.5, 125.2 (2 C), 129.6 (2 C), 137.3, 141.9.
Gen er a l P r oced u r e for Red u ction of 2-Vin yl-2-su lfi-
n yloxir a n es. A 25 mL round-bottomed flask was charged
with a solution of 1 equiv of the vinyl sulfinyl oxirane in DME
(ca. 0.1 M), and 7.2 equiv of TsNHNH2 was added, followed
by a solution of 9.5 equiv of NaOAc in H2O (0.2 mL/mmol).
The resulting mixture was refluxed for 2 h and stirred at room
temperature for 12 h, after which time it was diluted with CH2-
Cl2 (5 mL/mmol), and the layers were separated. The organic
layer was washed with a saturated solution of NaCl, dried over
anhydrous MgSO4, filtered, and concentrated under reduced
pressure to give a crude product which was purified by column
chromatography on silica gel (5-30% EtOAc-hexane).
Ack n ow led gm en t. This research was supported by
DGICYT (Grants No. PB96-0822 and PB94-0104). We
thank Dr. J . C. Lo´pez and Professor S. Valverde for
encouragement and support.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for all new compounds and
X-ray diffraction analyses data for 7d and 11a (51 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
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J O972358S