Nucleophilic epoxidation of α′-hydroxy vinyl sulfoxides

Article abstract of DOI:10.1021/jo026182s

The nucleophilic epoxidation of a variety of α′-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing scenario. The use of t-BuOOLi in Et₂O allows for a highly syn-selective epoxidation-oxidation. The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing (S,S_s) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In contrast, the (R,S_s) diastereomers (4e-g) show diminished reactivities and a very substrate-dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical correlations and an X-ray crystal structure.

Full text of DOI:10.1021/jo026182s

Nu cleop h ilic Ep oxid a tion of r′-Hyd r oxy Vin yl Su lfoxid es
Roberto Ferna´ndez de la Pradilla,*,† J orge Ferna´ndez,† Pilar Manzano,† Paloma Me´ndez,†
J ulia´n Priego,† Mariola Tortosa,† Alma Viso,† Mart´ın Mart´ınez-Ripoll,‡ and Ana Rodr´ıguez§
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva, 3, 28006 Madrid, Spain, Departamento de
Cristalografı´a, Instituto de Qu´ımica-Fı´sica Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain, and
Departamento de Quı´mica Inorga´nica, Orga´nica y Bioquı´mica, Facultad de Quı´micas,
Campus Universitario, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
iqofp19@iqog.csic.es
Received J uly 11, 2002
The nucleophilic epoxidation of a variety of R′-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has
been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities
and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing
scenario. The use of t-BuOOLi in Et2O allows for a highly syn-selective epoxidation-oxidation.
The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing
(S,SS) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In
contrast, the (R,SS) diastereomers (4e-g) show diminished reactivities and a very substrate-
dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical
correlations and an X-ray crystal structure.
In tr od u ction
from readily available (Z)- or (E)-alkenyl sulfoxides by
nucleophilic epoxidation with metalated peroxides.5,6
On the other hand, J ackson has shown that R′-(1-
hydroxyalkyl) vinyl sulfones undergo nucleophilic epoxi-
dation with good to excellent diastereoselectivity that
depends on allylic 1,2- and 1,3-strains and the presence
of a free or protected hydroxyl.7 Since related (E)-R′-(1-
hydroxyalkyl) vinyl sulfoxides are readily available enan-
Optically active epoxides are very attractive and
versatile building blocks for organic synthesis, and
therefore, the development of efficient routes to enan-
tioenriched epoxides has been an active area of research
for several decades. In this context, the Sharpless epoxi-
dation of allylic alcohols,1 along with more recent meth-
odologies to perform the asymmetric epoxidation of
unfunctionalized alkenes,2 are now fundamental pro-
cesses in organic synthesis. In contrast, the asymmetric
epoxidation of electron-deficient alkenes is comparatively
less well developed and is still being actively investi-
gated.3 The diastereoselective epoxidation of enantio-
merically pure alkenes may be a viable alternative route
to enantiopure oxiranes if the methodology meets several
requirements, such as readily available starting materi-
als, high diastereoselectivity, and usefulness of the
resulting oxiranes. A notable example of such a protocol
is the nucleophilic epoxidation of enantiopure (E)-N-(p-
tolylsulfonyl)vinylsulfoximines, available in four steps
from racemic methyl phenyl sulfoxide, with t-BuOOLi
that takes place with perfect geometric and facial selec-
tivity and in high yields.4 A few years ago, we reported
an efficient, general and novel methodology to prepare a
variety of optically pure sulfinyl and sulfonyl oxiranes
(3) For a review on applications of polymeric amino acids to this
field, see: (a) Ebrahim, S.; Wills, M. Tetrahedron: Asymmetry 1997,
8, 3163-3173. (b) Porter, M. J .; Roberts, S. M.; Skidmore, J . Bioorg.
Med. Chem. 1999, 7, 2145-2156. (c) For a recent review on asymmetric
epoxidations of electron-deficient olefins, see: Porte, M. J .; Skidmore,
J . Chem. Commun. 2000, 1215-1225. For leading references, see: (d)
Prabhakaran, E. N.; Nandy, J . P.; Shukla, S.; Iqbal, J . Tetrahedron
Lett. 2001, 42, 333-337. (e) Lygo, B.; To, D. C. M. Tetrahedron Lett.
2001, 42, 1343-1346. (f) Ray, P.; Roberts, S. M. J . Chem. Soc., Perkin
Trans. 1 2001, 149-153. (g) Nemoto, T.; Ohshima, T.; Shibasaki, M.
J . Am. Chem. Soc. 2001, 123, 9474-9475. (h) Bentley, P. A.; Flood, R.
W.; Roberts, S. M.; Skidmore, J .; Smith, C. B.; Smith, J . A. Chem.
Commun. 2001, 1616-1617. (i) Li, C.; Pace, E. A.; Liang, M.-C.;
Lobkovsky, E.; Gilmore, T. D.; Porco, J . A., J r. J . Am. Chem. Soc. 2001,
123, 11308-11309. (j) J acques, O.; Richards, S. J .; J ackson, R. F. W.
Chem. Commun. 2001, 2712-2713.
(4) (a) Meth-Cohn, O.; Moore, C.; Taljaard, H. C. J . Chem. Soc.,
Perkin Trans. 1 1988, 2663-2674. (b) Bailey, P. L.; Clegg, W.; J ackson,
R. F. W.; Meth-Cohn, O. J . Chem. Soc., Perkin Trans. 1 1990, 200-
202. (c) Bailey, P. L.; Clegg, W.; J ackson, R. F. W.; Meth-Cohn, O. J .
Chem. Soc., Perkin Trans. 1 1993, 343-350. (d) 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. (d) Briggs, A. D.; J ackson, R.
F. W.; Brown, P. A. J . Chem. Soc., Perkin Trans. 1 1998, 4097-4102.
For the preparation of enantiomerically enriched bromohydrins from
sulfoximinooxiranes, see: (e) Bailey, P. L.; Briggs, A. D.; J ackson, R.
F. W.; Pietruszka, J . Tetrahedron Lett. 1993, 34, 6611-6614. (f) Bailey,
P. L.; Briggs, A. D.; J ackson, R. F. W.; Pietruszka, J . J . Chem. Soc.,
Perkin Trans. 1 1998, 3359-3363.
† Instituto de Qu´ımica Orga´nica.
‡ Instituto de Qu´ımica-F´ısica Rocasolano.
§ Universidad de Castilla-La Mancha.
(1) (a) Katsuki, T. In Comprehensive Asymmetric Catalysis; J acob-
sen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999;
Chapter 18.1. (b) Katsuki, T.; Mart´ın, V. S. Org. React. 1996, 48, 1. (c)
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: Weinheim,
2000.
(2) (a) J acobsen, E. N.; Wu, M. H. In Comprehensive Asymmetric
Catalysis; J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
New York, 1999; Chapter 18.2. (b) Frohn, M.; Shi, Y. Synthesis 2000,
1979-2000. (c) See also ref 1c.
(5) (a) Ferna´ndez de la Pradilla, R.; Castro, S.; Manzano, P.; Priego,
J .; Viso, A. J . Org. Chem. 1996, 61, 3586-3587. (b) Ferna´ndez de la
Pradilla, R.; Castro, S.; Manzano, P.; Mart´ın-Ortega, M.; Priego, J .;
Viso, A. Rodr´ıguez, A.; Fonseca, I. J . Org. Chem. 1998, 63, 4954-4966.
(c) For the highly selective preparation of spirocyclic bis-sulfinyl
oxiranes by a related methodology, see: Aggarwal, V. K.; Barrell, J .
K.; Worrall, J . M.; Alexander, R. J . Org. Chem. 1998, 63, 7128-7129.
10.1021/jo026182s CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/24/2002
8166
J . Org. Chem. 2002, 67, 8166-8177

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
SCHEME 1
SCHEME 2
sequent oxidation with m-CPBA afforded the correspond-
ing racemic vinyl sulfoxides (()-3d and (()-4d (Scheme
2) that were readily separated by chromatography.
To address the influence of the geometry of the
substrate on the reactivity and diastereoselectivity of the
process, we prepared the previously unreported (Z)-R′-
hydroxy vinyl sulfoxides. At this stage, we chose to
prepare racemic materials since their synthesis could be
slightly shorter than that of the optically pure materials,
and they were judged to be adequate substrates for our
study on the diastereoselectivity of the process. We
envisioned that a straightforward entry to these products
could be the use of configurationally stable R-lithio
vinyl sulfides, trapping with an aldehyde, and hydroxyl-
directed oxidation to the corresponding sulfoxides. Thus,
the palladium-catalyzed hydrostannylation,12 of al-
kynyl sulfide 8, synthesized according to the protocol
of MaGee,13 gave stannane 9. Subsequent tin-lithium
metal exchange and addition to the appropriate aldehyde
gave R′-hydroxy vinyl sulfides (()-10e and (()-10f14 that
were oxidized with m-CPBA at -78 °C to afford the
corresponding sulfoxides (()-3e-f and (()-4e-f (Scheme
3), which were separated readily by chromatography. It
should be pointed out that the diastereoselectivity found
for the oxidation of (()-10f was highly dependent on the
solvent used, ranging from 90:8 in CH2Cl2, 63:21 in
CHCl3, to 67:33 in acetone, often accompanied by small
amounts of sulfone.
The second route explored entailed the direct metala-
tion of vinyl sulfide 11, synthesized in one step according
to the protocol of Truce,15 and subsequent addition to the
appropriate aldehyde to give sulfide (()-10g. Oxidation
with m-CPBA at -78 °C yielded the corresponding R′-
hydroxy vinyl sulfoxides (()-3g and (()-4g (Scheme 3)
that were separated readily by chromatography.
At this point, we considered that a study of the
behavior of the related R′-hydroxy vinyl sulfones would
provide a control experiment to evaluate the influence
of the sulfoxide functionality on the stereoselectivity of
the process. The corresponding sulfones 12a -f were
obtained in good yields by straightforward oxidation of
the appropriate sulfoxides (or sulfides) with MMPP or
m-CPBA (Table 1).
tiomerically pure,8 we considered that a study parallel
to J ackson’s,4,7 could shed additional light on the stereo-
chemical outcome of such processes and enhance their
synthetic usefulness, as well as extend the scope of our
own methodology. In this paper, we report a full account
of our efforts in this field,9 which have resulted in
methodology to prepare a variety of optically or diaste-
reomerically pure R′-(1-hydroxyalkyl) sulfinyl and sulfo-
nyl oxiranes from readily available alkenyl sulfoxides.
P r ep a r a tion of Su bstr a tes
To test the behavior of (E)-R′-hydroxy vinyl sulfoxides
and sulfones in the nucleophilic epoxidation, without
severe allylic 1,3 interactions, we prepared enantiopure
vinyl sulfoxides 1 and 2 according to the protocol of
Craig.10 Subsequent lithiation, with concomitant isomer-
ization, and addition to the corresponding aldehydes gave
the desired R′-hydroxy vinyl sulfoxides 3a -c and 4a -c
(Scheme 1), that were readily separated by chromatog-
raphy on silica gel.8
To extend our study to cyclic substrates, we prepared
racemic R′-hydroxy vinyl sulfide (()-6, by DIBALH
reduction of 2-phenylthio-2-cyclohexen-1-one, in turn
available in one step (81%) from cyclohexanone.11 Sub-
(6) For
a review on the preparation and applications of R-oxy
sulfones, including sulfonyl oxiranes, see: (a) Chemla, F. J . Chem. Soc.,
Perkin Trans. 1 2002, 275-299. For other reviews on aspects of the
synthesis and reactivity of sulfinyl and sulfonyl oxiranes, see: (b)
Satoh, T.; Yamakawa, K. Synlett 1992, 455-468. (c) Satoh, T. Chem.
Rev. 1996, 96, 3303-3325. For recent references on applications of
sulfinyl and sulfonyl oxiranes, see: (d) Mori, Y.; Hayashi, H. J . Org.
Chem. 2001, 66, 8666-8668. (e) Satoh, T.; Taguchi, D.; Kurabayashi,
A.; Kanoto, M. Tetrahedron 2002, 58, 4217-4224. (f) Mori, Y.; Hayashi,
H. Tetrahedron 2002, 58, 1789-1797.
(7) (a) J ackson, R. F. W.; Standen, S. P.; Clegg, W.; McCamley, A.
Tetrahedron Lett. 1992, 33, 6197-6200. (b) J ackson, R. F. W.; Standen,
S. P.; Clegg, W.; McCamley, A. J . Chem. Soc., Perkin Trans. 1 1995,
141-148. For a related study on the epoxidation of R′-hydroxycyclo-
hexenyl p-tolyl sulfones, see: (c) Bueno, A. B.; Carren˜o, M. C.; Garc´ıa
Ruano, J . L. Tetrahedron Lett. 1993, 34, 5007-5010.
(8) (a) Marino, J . P.; Viso, A.; Ferna´ndez de la Pradilla, R.;
Ferna´ndez, P. J . Org. Chem. 1991, 56, 1349-1351. (b) 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. (c) 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.
(9) For a preliminary communication, 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.
(12) Magriotis, P. A.; Brown, J . T.; Scott, M. A. Tetrahedron Lett.
1991, 32, 5047-5051.
(10) Craig, D.; Daniels, K.; McKenzie, A. R. Tetrahedron 1993, 49,
11263-11304.
(13) Kabanyane, S. T.; MaGee, D. I. Can. J . Chem. 1992, 70, 2758-
(11) (a) Monteiro, H. J . J . Org. Chem. 1977, 42, 2324-2326. Other
reducing agents tested (NaBH4, NaBH4/CeCl3, LiAlH4) gave inferior
results due to competing 1,4 reduction. (b) Vankar, Y. D.; Kumaravel,
G.; Bhattacharya, I.; Vankar, P. S.; Kaur, K. Tetrahedron 1995, 51,
4829-4840. (c) Takano, S.; Yamada, O.; Iida, H.; Ogasawara, K.
Synthesis 1994, 592-596.
2763.
(14) For an enantioselective synthesis of Z-hydroxyalkyl vinyl
sulfides, see: Berenguer, R.; Cavero, M.; Garc´ıa, J .; Mun˜oz, M.
Tetrahedron Lett. 1998, 39, 2183-2186.
(15) Truce, W. E.; Simms, J . A. J . Am. Chem. Soc. 1956, 78, 2756-
2759.
J . Org. Chem, Vol. 67, No. 23, 2002 8167

Ferna´ndez de la Pradilla et al.
TABLE 2. Ep oxid a tion of (E)-Hyd r oxy Vin yl Su lfon es
SCHEME 3
yielda
entry
substrate
conditions
anti
syn
(%)
1
2
3
4
5
12a (R1 ) Et)
M ) Li, THF 13a (50) 14a (50) 75
12b (R1 ) i-Pr) M ) Li, THF 13b (68) 14b (32) 63
12c (R1 ) t-Bu) M ) Li, THF 13c (75) 14c (25)
12c (R1 ) t-Bu) M ) Na, THF 13c (84) 14c (16)
12c (R1 ) t-Bu) M ) Li, Et2O 13c (20) 14c (80)
83
67
81
a
Yields of pure products after column chromatography.
analysis).8 In the E series, the main products were 3a -d
and in the Z series were 3e-g, all of which had lower
chromatographic mobility than their diastereomers 4a -d
and 4e-g, respectively.
Ep oxid a tion of (E)-r′-Hyd r oxy Vin yl Su lfoxid es
a n d Su lfon es
Our initial task was to establish the influence of the
allylic hydroxyl group in the selectivity of the process in
the absence of additional stereocenters. Table 2 shows
our results on the epoxidation of (E)-R′-hydroxy vinyl
sulfones. The first conditions examined were those used
by J ackson (entries 1-3). A general observation was that
the increase of the size of the substituent at the allylic
position produced a slight increase in the stereoselectivity
of the process, affording anti epoxides 1316 as main
products but with lower selectivities to those reported
for related substrates bearing a Ph group at the â carbon.
Apparently, the size of the substituent at the â position
plays a crucial role in this epoxidation.7 The effect of the
metal cation was examined and the use of t-BuOONa,
resulted in a slight enhancement of the reaction selectiv-
ity (entry 4). Finally, the effect of the solvent was briefly
studied, and the epoxidation of 12c with t-BuOOLi in
Et2O took place with inversion in the stereoselectivity of
the process and syn isomer 14c was the main product
(entry 5).
Next the influence of the sulfoxide in the viability and
stereoselectivity of the process was studied and the
results obtained are shown in Tables 3 and 4. Table 3
gathers our survey on the epoxidation of (S,SS)-R′-
hydroxy vinyl sulfoxides. After some experimentation
with t-BuOOLi in THF with poor results, the epoxidation
with t-BuOOLi was carried out in Et2O and syn-epoxy
sulfone 14a was obtained as practically a single diaste-
reomer (entry 1). In a previous report on the epoxidation
of simple vinyl and dienyl sulfoxides, we showed that the
use of t-BuOONa or t-BuOOK, frequently resulted in a
substantial enhancement of the reaction rate and selec-
tivity, along with less overoxidation to the corresponding
sulfones.5 These findings prompted us to test those
conditions on these fairly unreactive substrates, and in
fact, while t-BuOONa was not very effective in this case,
the use of t-BuOOK in THF gave anti-epoxy sulfoxide
TABLE 1. P r ep a r a tion of Hyd r oxy Vin yl Su lfon es
yielda
R3 substrate conditions product (%)
entry R1
R2
1
2
3
4
5
6
Et
n-Bu
H
H
H
3a
3b
3c
MMPPb 12a
75
i-Pr n-Bu
t-Bu n-Bu
Et
Ph
Et
MMPP
MMPP
12b
12c
73c
87
H
H
H
n-Bu (()-10e
m-CPBA (()-12e 74d
n-Bu (()-3f
MMPP
(()-12f
93
Ph
(()-4g
m-CPBA (()-12g 52e
a
b
Yields of pure products after column chromatography. Mag-
nesium monoperoxyphthalate hexahydrate. c Starting material
d
recovered (7%). Starting material (sulfide 10e) recovered (6%).
e Starting material recovered (28%).
The structures of these sulfoxides and sulfones were
1
assigned by spectroscopic methods, primarily by H and
13C NMR and comparison with other closely related
substrates previously prepared in our group or in the
literature. The geometry of our substrates conclusively
followed from the chemical shifts of the vinyl protons,
generally more shielded for Z isomers. For instance, the
shifts for the vinyl protons for the Et/n-Bu sulfoxide
examples are as follows: 4a (6.50 ppm, t, J ) 7.6 Hz),
4e (6.24 ppm, dd, J ) 8.9, 6.3 Hz), 3a (6.31 ppm, t, J )
7.6 Hz), 3e (6.18 ppm, dd, J ) 8.5, 6.8 Hz). The relative
stereochemistry of the R′-hydroxy vinyl sulfoxides was
deduced by comparison of spectral data and chromato-
graphic mobility with known products of comparable
structure (the absolute configuration of a product related
to 3a was established unequivocally by X-ray diffraction
(16) Throughout this paper relative anti/syn stereochemistries are
defined for the hydroxyl and epoxide functionalities, relative to the
extended conformation of the longest carbon chain.
8168 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
TABLE 3. Ep oxid a tion of (S,SS)-(E)-Hyd r oxy Vin yl Su lfoxid es
entry
substrate
conditions
A
B
C
D
yielda (%)
1
2
3
4
5
3a (R1 ) Et)
3a (R1 ) Et)
3b (R1 ) i-Pr)
3b (R1 ) i-Pr)
3c (R1 ) t-Bu)
M ) Li, Et2O
M ) K, THF
M ) K, THF
M ) Li, Et2O
M ) Li, Et2O
13a (5)
14a (95)
75
60
34b
60
88
15a (80)
15b (80)
16a (20)
16b (20)
13b (15)
13c (24)
14b (85)
14c (76)
a
b
Yields of pure products after column chromatography. Starting material recovered (41%).
TABLE 4. Ep oxid a tion of (R,SS)-(E)-Hyd r oxy Vin yl Su lfoxid es
entry
substrate
conditions
A
B
C
D
yielda (%)
1
2
3
4
4a (R1 ) Et)
4a (R1 ) Et)
4a (R1 ) Et)
4a (R1 ) Et)
4b (R1 ) i-Pr)
4c (R1 ) t-Bu)
M ) Li, THF
M ) Li, Et2O
M ) Na, THF
M ) K, THF
M ) Na, THF
ent-13a (28)
ent-13a (2)
ent-13a (8)
ent-13a (5)
ent-14a (72)
ent-14a (98)
ent-14a (21)
ent-14a (20)
70
73
18a (61)
18a (75)
18b (80)
60b
59
5
17b (20)
17c
6d
a
b
d
Yields of pure products after column chromatography. Starting material recovered (10%). c Starting material recovered (45%). See
text.
SCHEME 4
15a as the major product (entry 2) in fair yield. The
enhancement of the size of the allylic substituent resulted
in a substantial decrease in reactivity for 3b (entry 3)
and, especially, for 3c, which decomposed under these
conditions. In contrast, the use of t-BuOOLi in Et2O led
to an inversion in the selectivity of the process along with
overoxidation affording syn-epoxy sulfones 14b and 14c
in good yields.17
Table 4 shows our efforts on the epoxidation of (R,SS)-
R′-hydroxy vinyl sulfoxides 4. Entries 1 and 2 show the
results obtained for 4a with t-BuOOLi in THF and Et2O,
respectively, which gave syn-epoxy sulfone ent-14a as a
major product. In contrast, the epoxidation of 4a with
t-BuOONa or t-BuOOK in THF gave a fair yield of syn-
epoxy sulfoxide 18a . As observed before for diastereomers
3, the reactivity of the substrates diminished with the
increased steric bulk of the substituent at the allylic
position, with 4c affording complete decomposition under
these reaction conditions.
Ep oxid a tion of (Z)-r′-Hyd r oxy Vin yl Su lfoxid es
a n d Su lfon es
At this stage, we considered that changing the geom-
etry of the double bond would extend the scope of the
methodology and provide some insight into the stereo-
chemical outcome of the process. Our first efforts (Table
5) were directed to determine the influence of the
geometry of the double bond in the control of the allylic
alcohol on the diastereoselectivity of the process, in the
absence of additional elements of stereocontrol. To our
delight, the use of standard conditions (t-BuOOLi in
THF) gave excellent results in all cases examined,
affording anti isomers (()-13 as main products, indepen-
dently of the substituents at the R′ and â positions of the
vinyl sulfone (Table 5, entries 1, 2, and 4). In this case,
a change of solvent to Et2O (entry 3) did not have any
significant influence on the selectivity of the process.
Finally cyclic R′-hydroxy vinyl sulfoxides (()-3d and
(()-4d gave epoxy sulfoxides (()-15d and (()-17d as
major products indicating that the selectivity of the
process was independent of the configuration of the
sulfinyl moiety (Scheme 4).
(17) The use of recently titrated n-BuLi from old bottles to gen-
erate t-BuOOLi in Et2O often resulted in slow reactions and
a
substantial decrease in selectivity; this effect may be attributed to the
presence of relatively large amounts of lithium salts in the reaction
mixture.
J . Org. Chem, Vol. 67, No. 23, 2002 8169

Ferna´ndez de la Pradilla et al.
TABLE 5. Ep oxid a tion of (Z)-Hyd r oxy Vin yl Su lfon es
entry
substrate
R1
R3
conditions
anti
syn
yielda (%)
1
2
3
4
(()-12e
(()-12f
(()-12f
(()-12g
Et
Ph
Ph
Et
n-Bu
n-Bu
n-Bu
Ph
M ) Li, THF
M ) Li, THF
M ) Li, Et2O
M ) Li, THF
(()-13e (97)
(()-13f (93)
(()-13f (94)
(()-13g (100)
(()-14e (3)
(()-14f (7)
(()-14f (6)
76
86
68b
67
a
b
Yields of pure products after column chromatography. Starting material recovered (8%).
TABLE 6. Ep oxid a tion of (S,SS)-(Z)-Hyd r oxy Vin yl Su lfoxid es
entry
substrate
R1
R3
conditions
A
C
yielda (%)
1
2
3
4
5
6
(()-3e
(()-3e
(()-3f
(()-3f
(()-3g
(()-3g
Et
Et
Ph
Ph
Et
Et
n-Bu
n-Bu
n-Bu
n-Bu
Ph
M ) Na, THF
M ) Li, Et2O
M ) Na, THF
M ) Li, Et2O
M ) Na, THF
M ) Li, Et2O
(()-15e (100)
(()-15e (65)
(()-15f (98)
(()-15f (93)
(()-15g (100)
(()-15g (92)
90
80
85
67
90
80
(()-13e (35)
(()-13f (2)
(()-13f (7)
Ph
(()-13g (8)
a
Yields of pure products after column chromatography.
TABLE 7. Ep oxid a tion of (R,SS)-(Z)-Hyd r oxy Vin yl Su lfoxid es
entry
substrate
R1
R3
conditions
A
B
C
D
yielda (%)
1
2
3
4
5
(()-4e
(()-4e
(()-4f
(()-4f
(()-4g
Et
Et
Ph
Ph
Et
n-Bu
n-Bu
n-Bu
n-Bu
Ph
M ) Na, THF
M ) K, THF
M ) Na, THF
M ) Li, Et2O
M ) K, THF
(()-17e (67)
(()-17e (52)
(()-17f (78)
(()-18e (33)
40b
48c
68
(()-18e (48)
(()-18f (4)
(()-13f (18)
(()-13f (83)
(()-14f (17)
41d
79
(()-17g (15)
(()-18g (85)
a
b
Yields of pure products after column chromatography. Starting material recovered (42%). c Starting material recovered (45%).
d
Starting material recovered (20%).
Table 6 shows the results obtained for a variety of
vinyl sulfoxides under these epoxidation conditions.
Entries 1 and 2 indicate that the metal cation plays
an important role in the facial selectivity of the proc-
ess. Thus, the treatment of sulfoxide (()-4e with
t-BuOONa in THF provided a 67:33 mixture of anti- and
syn-epoxy sulfoxides (()-17e and (()-18e, while the
use of t-BuOOK gave a 52:48 mixture of anti- and syn-
epoxy sulfoxides. Interestingly, sulfoxide (()-4f with
t-BuOONa in THF displayed an excellent facial selec-
tivity, affording predominantly anti-epoxy sulfoxide
(()-17f along with some anti-epoxy sulfone (()-13f (entry
3). Entry 4 shows that the change of the solvent to
Et2O produces complete overoxidation, affording anti-
epoxy sulfone (()-13f as the major product with dimin-
ished selectivity. Finally, a reversal of selectivity using
t-BuOOK was found for substrate (()-4g (entry 5) that
racemic (Z)-(S,SS)-R′-hydroxy vinyl sulfoxides. In all
cases, the anti-epoxy sulfoxide (()-15 was the only
diastereomer obtained, along with small amounts of
the corresponding overoxidation products, anti-epoxy
sulfones (()-13 with t-BuOOLi. Furthermore, using
t-BuOONa in THF resulted in less overoxidation to the
sulfone (entry 3) or even avoided it (entries 1 and 5). It
should be mentioned that while the superior reactivity
of simple (Z)-alkenyl sulfoxides relative to their E isomers
in nucleophilic epoxidations has been noted before,5 the
very low reactivity found for (E)-R′-hydroxy vinyl sulfox-
ides prevented us from anticipating these very positive
results obtained for the Z counterparts.
The data gathered in Table 7 illustrates the some-
what more complex behavior of the Z (R,SS)-R′-hydroxy
8170 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
SCHEME 5
SCHEME 7
SCHEME 6
sulfones. In some cases, oxidation with MMPP was
sluggish and the reaction was then carried out with
m-CPBA or, when the latter also failed, with t-BuOOH/
VO(acac)2. It should be mentioned that the spectral
features of epoxy sulfone (()-13d were practically identi-
cal to those of the related p-tolyl analogue found in the
literature.7c
To determine the relative configuration of the epoxides
generated, we carried out chemical correlations shown
in Scheme 7. Desulfinylation of alkenyl sulfoxide (()-3c
with MeLi and t-BuLi in Et2O at -78 °C18 gave Z allylic
alcohol (()-19 that was epoxidized with m-CPBA to
produce syn-hydroxyoxirane (()-syn-20.19 On the other
hand, the treatment of epoxy sulfone 13c with sodium
amalgam in methanol gave the corresponding diastere-
omeric anti-epoxy alcohol anti-21, which had spectral
features consistent with the proposed structure. In ad-
dition, the structure of sulfinyl oxirane 18a was secured
by means of an X-ray diffraction analysis of the corre-
sponding p-nitrobenzoate 22, prepared in a standard
manner.20 In the case of Z isomers, our stereochemical
assignment relies on comparison of the spectral data of
anti-epoxy alcohol (()-23 obtained by treatment of epoxy
(18) Park, G.; Okamura, W. H. Synth. Commun. 1991, 21, 1047-
1054. See also ref 8b.
(19) The epoxidation of Z allylic alcohols with m-CPBA yields syn-
epoxy alcohols with high selectivity. (a) Pierre, J . L.; Chautemps, P.;
Arnaud, P. Bull. Soc. Chim. Fr. 1969, 1317-1321. (b) Sharpless, K.
B.; Michaelson, R. C. J . Am. Chem. Soc. 1973, 95, 6136-6137. (c)
Rossiter, B. E.; Verhoeven, T. R.; Sharpless, K. B. Tetrahedron Lett.
1979, 4729-4732.
provided a 15:85 mixture of anti- and syn-epoxy sulfox-
ides (()-17g and (()-18g.
(20) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ. UK
(entry code: TOTGEO).
Ch em ica l Cor r ela tion s
Schemes 5 and 6 summarize the oxidations carried out
to correlate the structures of epoxy sulfoxides and epoxy
J . Org. Chem, Vol. 67, No. 23, 2002 8171

Ferna´ndez de la Pradilla et al.
SCHEME 8
SCHEME 9
sulfoxide 15g with n-BuLi,21 with the known syn-epoxy
alcohol (()-25 diastereoisomeric to (()-23, described in
the literature,22 and obtained as the major product in the
epoxidation of (()-24.
Resu lts a n d Discu ssion
On the other hand, (Z)-R′-hydroxy vinyl sulfones
displayed higher anti selectivity than the E isomers
presumably through conformer A that now is further
stabilized by the lack of 1,3 interactions between R1 and
R2. In addition, the use of Et2O did not lead to any change
in the stereoselectivity of the process. This result may
be justified by considering that 1,3 allylic strain between
the sulfone and the â substituent in this case is a relevant
interaction, and this could destabilize conformer C for
this geometry. It should be mentioned that these obser-
vations are accommodated by J ackson’s model.
In the case of the epoxidations of hydroxy alkenyl
sulfoxides, our results cannot be rationalized by an early
transition state, and instead, we believe that the relative
stability of the transition states derives from the balance
of allylic 1,2- and 1,3-strains and the possibility of
concurrent coordination between the metalated peroxide
and the hydroxyl group and the sulfinyl oxygen. Consid-
ering this joint coordination as an important factor we
have carried out a detailed conformational analysis for
these substrates.24 Scheme 9 shows the proposed reactive
conformers for (Z)-alkenyl sulfoxides. Thus, for Z (S,SS)
isomers, D and E would be the reactive conformers, with
a predominant contribution of D due to a maximized
coordination (the sulfinyl oxygen is in closer proximity
to the allylic center than in E) and to a minimum allylic
1,2-strain between R2 and the bulky sulfinyl moiety. In
the case of Z (R,SS) isomers, F and G would be the
reactive conformers, with F allowing for maximum
For the sulfones, and assuming an early transition
state, the selectivity of the process may be understood
in terms of nucleophilic addition to the more stable
conformation, dictated by competing allylic 1,2 and 1,3
strains, followed by epoxide closure.7b J ackson suggested
that the stereochemistry of the process for â-unsubsti-
tuted vinyl sulfones (R2 ) R3 ) H) could be rationalized
on the basis of a reactive conformation in which 1,2 allylic
strain becomes dominant and an interaction between the
hydroxyl group and the reagent allows for delivery of the
reagent from the same face of the hydroxyl group (a
conformation similar to A, Scheme 8). On the other hand,
introduction of a phenyl substituent syn to the allylic
stereocenter (R2 ) Ph, R3 ) H) resulted in reversed
stereoselectivity. In that case, 1,3 allylic strain became
the main influence (the substantial destabilization of A
is a reflection of the coplanarity of the aromatic ring and
the double bond enforced by conjugation).7 The change
in the reactive conformation to B (Scheme 8) and the
interaction between the hydroxyl group and the reagent
accounts for the reversed stereoselectivity. In our study,
the moderate anti selectivity found for (E)-R′-hydroxy
vinyl sulfones in THF may be explained similarly by 1,2
allylic strain being the main influence and the increase
in selectivity with the increasing steric bulk of R1, making
A more stable than B (Scheme 8). On the other hand,
the remarkable reversal of facial selectivity found for 12c
in Et2O suggests formation of a chelated intermediate
leading to conformer C (Scheme 8) that minimizes 1,3
diaxial interactions and nucleophilic attack from the less
hindered â face to provide predominantly the syn iso-
mer.23 This interpretation also accommodates the results
obtained for the corresponding sulfoxides with t-BuOOLi
in Et2O by assuming initial oxidation to the sulfone.
(23) For leading references on sulfonyl participation in chelated
intermediates, see: (a) Marino, J . P.; Anna, L. J .; Ferna´ndez de la
Pradilla, R.; Mart´ınez, M. V.; Montero, C.; Viso, A. J . Org. Chem. 2000,
65, 6462-6473. (b) Yakura, T.; Tanaka, K.; Iwamoto, M.; Nameki, M.;
Ikeda, M. Synlett 1999, 1313-1315. (c) Marcantoni, E.; Cingolani, S.;
Bartoli, G.; Bosco, M.; Sambri, L J . Org. Chem. 1998, 63, 3624-3630.
(24) It should be noted that, for a simple Z-propenyl sulfoxide, the
energy difference between the more stable conformers (s-cis, CdC/Sd
(21) (a) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J . Org. Chem.
1989, 54, 3130-3136.
(22) Marples, B. A.; Rogers-Evans, M. Tetrahedron Lett. 1989, 30,
261-264.
O and s-cis, CdC/S-:) has been evaluated as just -0.4 kcal mol-1
.
See: Tietze, L. F.; Schuffenhauer, A.; Schreiner, P. R. J . Am. Chem.
Soc. 1998, 120, 7952-7958.
8172 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
SCHEME 10
the conformation of the allylic center is fixed and
therefore there is just one conformation about the C-S
bond that allows for joint coordination with the metal.
The increase in allylic 1,2-strain for M relative to L
accounts for the lower reactivity found for this isomer.
Con clu sion s
The nucleophilic epoxidation of a variety of R′-hydroxy
vinyl sulfoxides and sulfones has been studied. The
influence of the geometry of the alkene on the process
has been addressed and while the reactivity of E sulfox-
ides is low, the Z isomers are satisfactory substrates. In
some cases, the stereochemical outcome of the process
may be controlled by simply changing the reaction
conditions. We are currently examining the application
of this methodology to the synthesis of natural products
taking advantage of the rich chemistry of these sulfur-
containing oxiranes.4,6,7
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. Reagents and solvents were
handled by using standard syringe techniques. All reactions
were carried out under an argon atmosphere. Hexane, toluene,
and CH2Cl2 were distilled from CaH2, and THF and Et2O were
distilled from sodium. (MeO)2P(O)Me, Et3N, and i-Pr2NH were
distilled from CaH2. Crude products were purified by flash
chromatography on Merck 230-400 mesh silica gel with
distilled solvents. Analytical TLC was carried out on silica gel
plates with detection by UV light, iodine, acidic vanillin
solution, and 10% phosphomolybdic acid solution in ethanol.
All reagents were commercial products. Organolithium re-
agents were titrated prior to use.25 NaH and KH (60% in
mineral oil) were washed repeatedly with dry hexane and dried
prior to use. Through this section, the volume of solvents is
reported in mL/mmol of starting material. 1H and 13C NMR
spectra were recorded at 200, 300, or 400 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 ap-
propriate: s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), br (broad). Melting points are uncorrected. Optical
rotations were measured at 20 °C using a sodium lamp and
in CHCl3 solution. Low-resolution mass spectra were recorded
by direct injection using the electronic impact technique with
an ionizacion energy of 70 eV or using the atmospheric
pressure chemical ionizacion (APCI) or electrospray (ES)
chemical ionizacion techniques in its positive or negative
modes. Elemental analyses were carried out at Instituto de
Qu´ımica Orga´nica, CSIC, Madrid.
Gen er a l P r oced u r e for Syn th esis of (E)-Hyd r oxy Vin yl
Su lfoxid es. A round-bottomed flask was charged with THF
(3.5 mL/mmol) and 2.6 equiv of freshly distilled i-Pr2NH and
cooled to -78 °C. To the above solution was added 2.5 equiv
of n-BuLi, and the resulting LDA solution (ca. 0.3 M) was
stirred at this temperature. After 10 min, a solution of 1 equiv
of a mixture of vinyl sulfoxides in THF (2 mL/mmol), previ-
ously dried over 4 Å sieves, was added dropwise slowly (ca. 8
min/mmol of sulfoxide) to produce a pale yellow solution. After
the solution was stirred for an additional 10 min at -78 °C, 5
equiv of freshly distilled aldehyde was added dropwise and
the resulting colorless solution was stirred at this temperature
for 10 min. The reaction mixture was quenched with a
saturated solution of NH4Cl (2 mL/mmol) and H2O (2 mL/
mmol) and diluted with EtOAc (3 mL/mmol), and the layers
were separated. The aqueous layer was extracted with EtOAc
SCHEME 11
coordination but with a significant contribution of allylic
1,2-strain; in contrast, G minimizes allylic 1,2-strain but
allylic 1,3-strain is higher and joint coordination is now
less effective. This balance of effects allows for the
prediction of a diminished selectivity for these isomers.
Thus, for a small R2 (4e, 4f, R2 ) n-Bu), both conformers
are operative and the selectivity of the process is deter-
mined by the size of R1, with low selectivity for the small
R1 ) Et, and with anti selectivity for R1 ) Ph due to
substantial 1,2-strain in F . On the other hand for R2 )
Ph, 4g, the participation of F is much more important to
minimize 1,3-strain and a syn selectivity is observed.
In the case of E (S,SS) isomers, H and I would be the
reactive conformers (Scheme 10), and considering that
for R1 ) Et the balance of 1,2- and 1,3-allylic strains is
similar for R2 ) n-Bu, as deduced from the results for
the corresponding sulfone, a predominant contribution
of H due to a maximized coordination would be ex-
pected to produce the anti isomer with high selectivity.
In the case of E (R,SS) isomers, J and K would be the
reactive conformers (Scheme 10), with J allowing for
maximum coordination and leading mainly to the syn
isomer, and with K destabilized by 1,3-allylic strain
between R1 and R2.
Scheme 11 gathers the reactive conformations for the
diastereomeric cyclohexenyl sulfoxides. In these cases,
(25) Watson, S. C.; Eastham, J . E. J . Organomet. Chem. 1967, 9,
165-168.
J . Org. Chem, Vol. 67, No. 23, 2002 8173

Ferna´ndez de la Pradilla et al.
(three times, 4 mL/mmol). The combined organic extracts were
washed with a saturated solution of NaCl (4 mL/mmol), dried
over MgSO4, and concentrated under reduced pressure to
give a crude product that was purified by column chromatog-
raphy (CH2Cl2-EtOAc mixtures) to give pure hydroxy vinyl
sulfoxides.
filtered, and concentrated under reduced pressure to give a
crude product that was purified by column chromatography
(EtOAc-CH2Cl2) to give the desired hydroxy vinyl sulfoxides.
Syn t h esis of (()-(Z)-1-P h en yl-2-(SS)-(p -t olylsu lfin yl)-
2-en -1-(S)-ol, 3f, a n d (()-(Z)-1-P h en yl-2-(SS)-(p-tolylsu lfi-
n yl)-2-en -1-(R)-ol, 4f. From hydroxy vinyl sulfide 10f (1.2 g,
3.80 mmol), m-CPBA (936 mg, 3.80 mmol, 70%), and K2CO3
(1.6 g, 11.40 mmol), according to the general procedure in
CH2Cl2 (2 h), a 90:8:1:1 mixture of 3f, 4f, 10f, and 12f was
obtained. Direct recrystallization from the crude (1% EtOAc-
hexane) gave 1.03 g (3.18 mmol, 84%) of 3f. Purification by
chromatography of the mother liquours gave 12 mg (0.04
mmol, 1%) of 10f, 15 mg (0.04 mmol, 1%) of sulfone 12f, 85
mg (0.26 mmol, 7%) of 4f, as a white solid recrystallized from
Et2O-hexane, and 8 mg (0.02 mmol) of 3f. When the reaction
was carried out in acetone, a 67:33 mixture of 3f and 4f was
obtained (91%). Data for 3f: mp 104-106 °C; Rf ) 0.20 (10%
Syn th esis of (+)-(E)-2,2-Dim eth yl-4-(SS)-(p-tolylsu lfi-
n yl)n on -4-en -3(S)-ol, 3c, a n d (+)-(E)-2,2-Dim eth yl-4-(SS)-
(p-tolylsu lfin yl)n on -4-en -3(R)-ol, 4c. From i-Pr2NH (0.68
mL, 525 mg, 5.16 mmol) in 18 mL of THF with n-BuLi (1.6 M,
3.10 mL, 4.96 mmol), a solution of the mixture of vinyl
sulfoxides 1 and 2 (440 mg, 1.98 mmol) in 1.5 mL of THF, and
pivalaldehyde (1.07 mL, 849 mg, 9.86 mmol), according to the
general procedure, was obtained a 72:28 mixture of hydroxy
vinyl sulfoxides 3c and 4c. Purification by column chroma-
tography (0-40% EtOAc-CH2Cl2) gave 89 mg (15%) of 4c as
a white solid, recrystallized from 5% EtOAc-hexane, 269 mg
(44%) of 3c as a white solid, recrystallized from 5% EtOAc-
hexane, and 120 mg (20%) of a mixture of these alcohols. Data
1
EtOAc-CH2Cl2); H NMR (300 MHz) δ 0.89 (t, 3 H, J ) 7.1
Hz), 1.24-1.42 (m, 4 H), 2.35 (m, 1 H), 2.43 (s, 3 H), 2.65 (m,
1 H), 4.33 (s, 1 H), 5.46 (s, 1 H), 5.64 (dd, 1 H, J ) 8.3, 6.8
Hz), 7.00-7.04 (m, 2 H), 7.16-7.26 (m, 3 H), 7.34 (d, 2 H, J )
8.3 Hz), 7.49 (d, 2 H, J ) 8.3 Hz); 13C NMR (50 MHz) δ 13.7,
21.3, 22.2, 28.6, 31.1, 71.1, 124.3 (2 C), 126.5 (2 C), 127.4, 128.1
(2 C), 130.0 (2 C), 139.0, 139.8, 141.2, 146.3. Data for 4f: mp
72-73 °C; Rf ) 0.40 (10% EtOAc-CH2Cl2); 1H NMR (200 MHz)
δ 0.87 (t, 3 H, J ) 7.0 Hz), 1.20-1.44 (m, 4 H), 2.17-2.34 (m,
1 H), 2.37 (s, 3 H), 2.44-2.63 (m, 1 H), 3.31 (d, 1 H, J ) 4.8
Hz), 5.70 (d, 1 H, J ) 4.8 Hz), 5.89 (dd, 1 H, J ) 8.8, 6.7 Hz),
7.18-7.32 (m, 7 H), 7.47 (d, 2 H, J ) 8.2 Hz); 13C NMR (50
MHz) δ 13.7, 21.3, 22.2, 28.6, 30.9, 71.2, 124.8 (2 C), 126.4 (2
C), 127.2, 128.0 (2 C), 129.9 (2 C), 140.2, 140.9, 141.0, 141.3,
146.1.
for 3c: mp 85-86 °C; Rf ) 0.26 (10% EtOAc-CH2Cl2); [R]20
D
1
) +174.8 (c ) 0.491); H NMR (200 MHz) δ 0.87 (t, 3 H, J )
7.1 Hz), 0.99 (s, 9 H), 1.21-1.48 (m, 4 H), 2.21-2.55 (m, 3 H),
2.38 (s, 3 H), 3.80 (d, 1 H, J ) 4.8 Hz), 6.30 (t, 1 H, J ) 7.6
Hz), 7.27 (d, 2 H, J ) 8.1 Hz), 7.53 (d, 2 H, J ) 8.2 Hz); 13C
NMR (50 MHz) δ 13.8, 21.4, 22.4, 26.8 (3 C), 29.5, 31.4, 37.5,
78.9, 126.4 (2 C), 130.0 (2 C), 135.5, 141.0, 142.1, 143.5. Data
for 4c: mp 118-119 °C; Rf ) 0.37 (10% EtOAc-CH2Cl2); [R]20
D
1
) +169.0 (c ) 1.18); H NMR (300 MHz) δ 0.89 (t, 3 H, J )
7.2 Hz), 1.02 (s, 9 H), 1.16 (d, 1 H, J ) 4.0 Hz), 1.27-1.50 (m,
4 H), 2.19-2.27 (m, 2 H), 2.36 (s, 3 H), 4.39 (d, 1 H, J ) 4.0
Hz), 6.71 (dd, 1 H, J ) 8.1, 7.0 Hz), 7.22 (d, 2 H, J ) 7.8 Hz),
7.57 (d, 2 H, J ) 8.3 Hz); 13C NMR (50 MHz) δ 13.8, 21.3,
22.4, 26.5 (3 C), 29.0, 31.1, 37.3, 76.5, 125.6 (2 C), 129.6 (2 C),
134.8, 141.1, 144.0, 145.2.
Gen er a l P r oced u r e for Syn th esis of (Z)-Hyd r oxy Vin yl
Su lfid es. To a cold (-78 °C) solution of vinylstannane 9 in
THF (5 mL/mmol) was added 1.1 equiv of n-BuLi. After 30
min, a solution of 2-3 equiv of aldehyde in THF (1 mL/mmol
of aldehyde) was added. After 15 min, the reaction was
quenched with saturated NH4Cl (3 mL/mmol) and H2O (3 mL/
mmol). The aqueous layer was extracted with EtOAc (three
times, 4 mL/mmol), and the combined organic extracts were
washed with a saturated solution of NaCl, dried over anhy-
drous MgSO4, filtered, and concentrated under reduced pres-
sure. The resulting crude reaction mixture was purified by
column chromatography on silica gel.
Syn th esis of (()-(Z)-1-P h en yl-2-(p-tolylsu lfen yl)h ep t-
2-en -1-ol, 10f. From stannane 9 (6.00 g, 12.10 mmol), n-BuLi
(9.1 mL, 1.6 M, 14.52 mmol), and 2 equiv of benzaldehyde (2.45
mL, 2.56 g, 24.20 mmol), following the general procedure, a
94:6 mixture of hydroxy sulfide 10f and vinyl sulfide 10e′ was
obtained. Purification by chromatography gave 158 mg (0.76
mmol, 6%) of 10e′ and 3.53 g (11.3 mmol, 93%) of 10f as
colorless oils. Data for 10f: Rf ) 0.22 (10% EtOAc-hexane);
1H NMR (200 MHz) δ 0.87 (t, 3 H, J ) 7.1 Hz), 1.20-1.45 (m,
4 H), 2.29 (s, 3 H), 2.32 (m, 2 H), 2.44 (d, 1 H, J ) 5.0 Hz),
5.15 (d, 1 H, J ) 4.4 Hz), 6.27 (dd, 1 H, J ) 7.2, 1.1 Hz), 7.04
(d, 2 H, J ) 8.2 Hz), 7.14 (d, 2 H, J ) 8.4 Hz), 7.26-7.32 (m,
5 H); 13C NMR (50 MHz) δ 13.9, 20.9, 22.4, 29.4, 31.1, 76.5,
126.7 (2 C), 127.6, 128.2 (2 C), 129.1 (2 C), 129.7 (2 C), 131.7,
135.8, 136.0, 139.0, 141.8.
Gen er a l P r oced u r e for Oxid a tion of Su lfoxid es w ith
MMP P . To a cold (0 °C) solution of sulfoxide in MeOH (10
mL/mmol) was added 1.5-1.8 equiv of magnesium monoper-
oxyphthalate hexahydrate (MMPP). The mixture was stirred
from 0 °C to room temperature, monitored by TLC until
completion, and then quenched with a saturated solution of
NaHCO3 (4 mL/mmol). After removal of MeOH under reduced
pressure, the mixture was diluted with EtOAc (5 mL/mmol),
the layers were separated, and the aqueous phase was
extracted with EtOAc (three times, 4 mL/mmol). The combined
organic layers were washed with a saturated solution of NaCl
(1 mL/mmol), dried over MgSO4, filtered, and concentrated
under reduced pressure to give a crude product that was
purified by gradient column chromatography using EtOAc-
hexane mixtures.
Syn th esis of (()-(Z)-1-P h en yl-2-(p-tolylsu lfon yl)h ep t-
2-en -1-ol, 12f. From hydroxy vinyl sulfoxide 3f (66 mg, 0.20
mmol) in MeOH (2 mL) and MMPP (198 mg, 0.40 mmol),
according to the general procedure (22 h), after chromatogra-
phy (CH2Cl2) was obtained vinyl sulfone 12f (64 mg, 93%) as
a white solid, further recrystallized from 5% EtOAc-hexane.
Data for 12f: mp 44-45 °C; Rf ) 0.48 (5% EtOAc-CH2Cl2);
1H NMR (200 MHz) δ 0.79 (t, 3 H, J ) 6.9 Hz), 1.17-1.24 (m,
4 H, 2 H-5), 2.38 (s, 3 H), 2.48 (m, 2 H), 3.51 (d, 1 H, J ) 5.6
Hz), 5.67 (d, 1 H, J ) 5.5 Hz), 6.10 (dd, 1 H, J ) 7.9, 7.3 Hz),
7.20 (d, 2 H, J ) 8.0 Hz), 7.26 (s, 5 H), 7.56 (d, 2 H, J ) 8.4
Hz); 13C NMR (50 MHz) δ 13.7, 21.5, 22.3, 28.3, 30.6, 73.6,
126.6 (2 C), 127.3 (2 C), 127.8, 128.3 (2 C), 129.5 (2 C), 138.6,
140.3, 143.7, 144.1, 146.7.
Gen er a l P r oced u r e for Oxid a tion of Hyd r oxy Vin yl
Su lfid es. To a solution of the hydroxy vinyl sulfide in acetone
(5 mL/mmol) was added 3.0 equiv of K2CO3, the mixture was
cooled to -78 °C, 1.1 equiv of 70% m-CPBA was added, and
the reaction mixture was allowed to warm slowly to room
temperature and monitored by TLC. The reaction was quenched
with 1 M aqueous Na2S2O4 (4 mL/mmol) and a saturated
solution of NaHCO3 (2 mL/mmol) and extracted with EtOAc
(three times, 4 mL/mmol). The organic layer was washed with
a saturated solution of NaHCO3 (4 mL/mmol) and with a
saturated solution of NaCl (4 mL/mmol), dried over MgSO4,
Gen er a l P r oced u r e for Nu cleop h ilic Ep oxid a tion of
Vin yl Su lfon es a n d Su lfoxid es. (a ) With t-Bu OOLi. A two-
necked round-bottomed flask fitted with a tube in T for
entrance and exit of argon and a polyethylene stopper was
charged with anhydrous THF (5 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 (5 mL/mmol), previously
dried over 4 Å sieves, was added dropwise. The reaction
mixture was stirred at 0 °C until starting material disappear-
8174 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
ance, monitored by TLC. The reaction was then quenched with
a 1 M 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, 10 mL/mmol),
Purification by chromatography (0-10% EtOAc-CH2Cl2) gave
23 mg (62%) of 13e as a colorless oil and 5 mg (14%) of a
mixture of 13e and 14e. Data for 13e: Rf ) 0.34 (30% EtOAc-
1
hexane); H NMR (200 MHz) δ 0.92 (t, 3 H, J ) 7.3 Hz), 0.94
and the combined organic extracts were washed with
a
(t, 3 H, J ) 7.3 Hz), 1.34-1.60 (m, 4 H), 1.95-2.04 (m, 2 H),
2.14 (dt, 2 H, J ) 14.8, 6.6 Hz, 2.44 (s, 3 H), 3.34 (t, 1 H, J )
6.4 Hz), 3.68 (br d, 1 H, J ) 8.4 Hz), 7.36 (d, 2 H, J ) 8.6 Hz),
7.77 (d, 2 H, J ) 8.4 Hz); 13C NMR (50 MHz) δ 9.9, 13.8, 21.7,
22.3, 26.4, 29.1, 62.8, 69.0, 77.4, 129.0 (2 C), 129.9 (2 C), 135.0,
145.4. The data found for 14e was identical to that described
below.
Syn th esis of (+)-(1′S,2R,3R,SS)-3-n -Bu tyl-2-(1′-h yd r oxy-
p r op yl)-2-(p-tolylsu lfin yl)oxir a n e, 15a , (+)-(1′S,2S,3S,SS)-
3-n -Bu t yl-2-(1′-h yd r oxyp r op yl)-2-(p -t olylsu lfin yl)ox-
ir a n e, 16a , (-)-(1′S,2S,3S)-3-n -Bu tyl-2-(1′-h ydr oxyp r op yl)-
2-(p-tolylsu lfon yl)oxir a n e, 14a , a n d (+)-(1′S,2R,3R)-3-n -
Bu tyl-2-(1′-h ydr oxypr opyl)-2-(p-tolylsu lfon yl)oxir an e, 13a.
From t-BuOOH (70 µL, 63 mg, 0.7 mmol) in Et2O (3.50 mL),
with n-BuLi (1.6 M, 0.44 mL, 0.7 mmol) and a solution of vinyl
sulfoxide 3a (38 mg, 0.14 mmol) in Et2O (1.0 mL), according
to the general procedure (24 h), was obtained a 5:95 mixture
of epoxy sulfones 13a and 14a . Purification by chromatography
(5-30% EtOAc-hexane) gave 32 mg (75%) of 14a .
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 chroma-
tography on silica gel, using a gradient of mixtures of EtOAc-
hexane or EtOAc-CH2Cl2.
(b) With t-Bu OONa or t-Bu OOK. A two-necked round-
bottomed flask fitted with a tube in T for entrance and exit of
argon and a polyethylene stopper was charged with anhydrous
THF (5 mL/mmol) and 2-4 equiv of oil-free NaH or KH, the
mixture was cooled to 0 °C, and then 2-4 equiv of t-BuOOH
(80% in t-BuOO-t-Bu) was added. After being stirred at room
temperature for 20-30 min, the resulting solution was cooled
to 0 °C and a solution of 1 equiv of the corresponding vinyl
sulfoxide in THF (2-5 mL/mmol), previously dried over 4 Å
sieves, was added dropwise. The reaction mixture was stirred
at 0 °C until starting material disappearance, monitored by
TLC. Isolation and purification were performed as described
above.
Syn th esis of (+)-(1′S,2R,3R)-3-n -Bu tyl-2-(1′-h yd r oxy-
2′,2′-d im eth ylp r op yl)-2-(p-tolylsu lfon yl)oxir a n e, 13c, a n d
(-)-(1′S,2S,3S)-3-n -Bu tyl-2-(1′-h yd r oxy-2′,2′-d im eth ylp r o-
p yl)-2-(p-tolylsu lfon yl)oxir a n e, 14c. From t-BuOOH (31 µL,
22 mg, 0.249 mmol) in THF (1.50 mL), with n-BuLi (1.6 M,
0.19 mL, 0.304 mmol) and a solution of vinyl sulfone 12c (33
mg, 0.102 mmol) in THF (0.80 mL), according to the general
procedure (0 °C, 3 h), was obtained a 75:25 mixture of epoxy
sulfones 13c and 14c. Purification by chromatography (0-20%
EtOAc-hexane) gave 21 mg (60%) of 13c as a white solid
recrystallized from 5% EtOAc-hexane and 8 mg (23%) of 14c
as a colorless oil.
From t-BuOOH (31 µL, 22 mg, 0.249 mmol) in Et2O (1.50
mL), with n-BuLi (1.16 M, 0.27 mL, 0.313 mmol) and a solution
of vinyl sulfone 12c (25 mg, 0.077 mmol) in Et2O (0.50 mL),
according to the general procedure (0 °C, 64 h), was obtained
a 20:80 mixture of epoxy sulfones 13c and 14c. Purification
by chromatography (60-100% CH2Cl2-hexane) gave 5 mg
(19%) of 13c and 16 mg (62%) of 14c.
From KH (6 mg, 0.14 mmol) in THF (1.0 mL), t-BuOOH
(17 µL, 15 mg, 0.17 mmol), and a solution of vinyl sulfoxide
3a (19 mg, 0.07 mmol) in THF (0.30 mL), according to the
general procedure (15 min), was obtained an 80:20 mixture of
epoxy sulfoxides 15a and 16a . Purification by chromatography
(CH2Cl2-50% EtOAc/CH2Cl2) gave 9 mg (45%) of 15a as a white
solid and 3 mg (15%) of 16a as a colorless oil. Data for 15a :
mp 108-110 °C; Rf ) 0.32 (20% EtOAc-CH2Cl2); [R]20
)
D
1
+184.6 (c ) 1.40); H NMR (200 MHz) δ 0.87 (t, 3 H, J ) 6.9
Hz), 1.03 (t, 3 H, J ) 7.3 Hz), 1.23-1.46 (m, 4 H), 1.64-1.84
(m, 4 H), 2.40 (s, 3 H), 2.64 (d, 1 H, J ) 5.1 Hz), 3.18 (dd, 1 H,
J ) 7.1, 5.3 Hz), 3.71 (dt, 1 H, J ) 8.9, 4.8 Hz), 7.30 (d, 2 H,
J ) 8.0 Hz), 7.52 (d, 2 H, J ) 8.2 Hz); 13C NMR (50 MHz) δ
10.5, 13.8, 21.5, 22.3, 26.7, 27.2, 28.7, 60.9, 71.1, 78.8, 126.3
(2 C), 129.7 (2 C), 135.4, 142.7. Data for 16a : Rf ) 0.33 (20%
EtOAc-CH2Cl2); [R]20D ) +34.0 (c ) 0.50); 1H NMR (300 MHz)
δ 0.74 (t, 3 H, J ) 7.3 Hz), 0.90 (t, 3 H, J ) 7.3 Hz), 1.24-1.52
(m, 6 H), 1.60-1.68 (m, 1 H), 1.79-1.85 (m, 1 H), 2.41 (s, 3
H), 2.70 (d, 1 H, J ) 5.4 Hz), 3.37 (dd, 1 H, J ) 7.6, 4.7 Hz),
4.02 (dt, 1 H, J ) 8.9, 5.1 Hz), 7.31 (d, 2 H, J ) 8.2 Hz), 7.55
(d, 2 H, J ) 8.2 Hz); 13C NMR (50 MHz) δ 10.2, 13.8, 21.5,
22.3, 27.1, 27.9, 29.0, 63.0, 71.3, 77.4, 125.8 (2 C), 129.7 (2 C),
135.9, 142.5.
From NaH (4.2 mg, 0.175 mmol) in THF (1.10 mL),
t-BuOOH (21 µL, 15 mg, 0.166 mmol), and a solution of vinyl
sulfone 12c (11 mg, 0.034 mmol) in THF (0.30 mL), according
to the general procedure (0 °C, 3 h), was obtained an 84:16
mixture of epoxy sulfones 13c and 14c. Purification by
chromatography (0-20% EtOAc-hexane) gave 8 mg (67%) of
a mixture of 13c and 14c. Data for 13c: mp 98-99 °C; Rf )
0.35 (20% EtOAc-hexane); [R]20D ) +16.6 (c ) 1.76); 1H NMR
(300 MHz, 40 °C) δ 0.84 (t, 3 H, J ) 7.1 Hz), 1.12 (s, 9 H),
1.20-1.40 (m, 4 H), 1.44-1.70 (m, 2 H), 2.44 (s, 3 H), 2.72
(dd, 1 H, J ) 6.5, 5.5 Hz), 3.34 (d, 1 H, J ) 10.6 Hz), 3.47 (d,
1 H, J ) 9.5 Hz), 7.33 (d, 2 H, J ) 8.1 Hz), 7.76 (d, 2 H, J )
8.3 Hz); 13C NMR (50 MHz) δ 13.8, 21.7, 22.2, 26.9, 27.1 (3 C),
28.2, 36.4, 62.3, 76.0, 79.4, 128.3 (2 C), 129.7 (2 C), 133.6, 145.6.
Syn th esis of (+)-(1′R,2S,3S)-3-n -Bu tyl-2-(1′-h yd r oxy-
p r op yl)-2-(p-tolylsu lfon yl)oxir a n e, en t-13a , (-)-(1′R,2R,-
3R )-3-n -B u t y l-2-(1′-h y d r o x y p r o p y l)-2-(p -t o ly ls u lfo -
n yl)oxir a n e, en t-14a , a n d (+)-(1′R,2R,3R,SS)-3-n -Bu tyl-
2-(1′-h ydr oxyp r opyl)-2-(p-tolylsu lfin yl)oxir a n e, 18a . From
t-BuOOH (18 µL, 16 mg, 0.20 mmol) in Et2O (1.0
mL), with n-BuLi (1.6 M, 0.12 mL, 0.2 mmol) and a solu-
tion of vinyl sulfoxide 4a (15 mg, 0.05 mmol) in Et2O (0.35
mL), according to the general procedure (24 h), was ob-
tained a 98:2 mixture of epoxy sulfones ent-14a and ent-13a .
Purification by chromatography (0-30% EtOAc-hexane) gave
11.9 mg (70%) of ent-14a , and 0.5 mg (3%) of ent-13a , as color-
less oils with identical spectral data to that described before.
Similarly, when the reaction was carried out in THF (5 h), a
72:28 mixture of ent-14a and ent-13a was obtained (70%).
From NaH (18 mg, 0.45 mmol) in THF (2.5 mL), t-BuOOH
(56 µL, 50 mg, 0.45 mmol) and a solution of vinyl sulfoxide 4a
(42 mg, 0.15 mmol) in THF (1.0 mL), according to the general
procedure (45 min), a 10:21:8:61 mixture of starting material,
epoxy sulfones ent-14a , ent-13a and epoxy sulfoxide 18a was
obtained. Purification by chromatography (5-50% EtOAc-
hexane) gave 7 mg (13%) of ent-14a , 3 mg (6%) of ent-13a , and
22 mg (41%) of 18a as colorless oils.
Data for 14c: Rf ) 0.29 (20% EtOAc-hexane); [R]20 ) -51.8
D
(c ) 0.345); 1H NMR (300 MHz) δ 0.86 (s, 9 H), 0.87 (t, 3 H, J
) 7.1 Hz), 1.23-1.47 (m, 4 H), 1.66-1.78 (m, 1 H), 1.84-1.93
(m, 1 H), 2.40 (d, 1 H, J ) 6.4 Hz), 2.44 (s, 3 H), 3.40 (dd, 1 H,
J ) 8.2, 4.5 Hz), 4.17 (d, 1 H, J ) 6.3 Hz), 7.33 (d, 2 H, J ) 8.5
Hz), 7.76 (d, 2 H, J ) 8.3 Hz); 13C NMR (50 MHz) δ 13.9, 21.8,
22.3, 26.6 (3 C), 27.5, 29.0, 35.9, 61.6, 76.5, 78.6, 129.6 (2 C),
130.0 (2 C), 132.1, 145.6.
Syn t h esis of (()-(1′S,2R,3S)-3-n -Bu t yl-2-(1′-h yd r oxy-
pr opyl)-2-(p-tolylsu lfon yl)oxir an e, 13e, an d (()-(1′S,2S,3R)-
3-n -Bu t yl-2-(1′-h yd r oxyp r op yl)-2-(p -t olylsu lfon yl)ox-
ir a n e, 14e. From t-BuOOH (47 µL, 34 mg, 0.377 mmol) in THF
(2.5 mL), with n-BuLi (2.0 M, 0.24 mL, 0.47 mmol) and a
solution of vinyl sulfone 12e (35 mg, 0.118 mmol) in THF (1.0
mL), according to the general procedure (0 °C, 20 h), was
obtained a 97:3 mixture of epoxy sulfones 13e and 14e.
From KH (7 mg, 0.18 mmol) in THF (1.5 mL), t-BuOOH
(22 µL, 20 mg, 0.18 mmol), and a solution of vinyl sulfoxide
4a (24 mg, 0.09 mmol) in THF (0.6 mL), according to the
J . Org. Chem, Vol. 67, No. 23, 2002 8175

Ferna´ndez de la Pradilla et al.
general procedure (45 min), was obtained a 20:5:75 mixture
of epoxy sulfones ent-14a , ent-13a , and epoxy sulfoxide 18a .
Purification by chromatography (5-30% EtOAc-hexane) gave
4 mg (15%) of ent-14a and 11 mg (44%) of 18a as colorless
3S,SS)-3-P h en yl-2-(1′-h yd r oxyp r op yl)-2-(p-tolylsu lfin yl)-
oxir a n e, 18g. From KH (7 mg, 0.17 mmol) in THF (1.0 mL),
t-BuOOH (22 µL, 16 mg, 0.18 mmol), and a solution of vinyl
sulfoxide 4g (13 mg, 0.043 mmol) in THF (0.30 mL), according
to the general procedure (-20 to +4 °C, 92 h), was obtained a
15:85 mixture of epoxy sulfoxides 17g and 18g. Purification
by chromatography (0-60% EtOAc-CH2Cl2) gave 7 mg (50%)
of 18g, as a white solid, recrystallized from 5% EtOAc-hex-
ane, 3 mg (21%) of a mixture of 17g and 18g and 1 mg (8%) of
starting material. Data for 17g: Rf ) 0.32 (5% EtOAc-
CH2Cl2); 1H NMR (200 MHz) δ 1.01 (t, 3 H, J ) 7.3 Hz), 1.62-
1.77 (m, 1 H), 1.87 (d, 1 H, J ) 3.5 Hz), 1.94-2.06 (m, 1 H),
2.42 (s, 3 H), 3.92 (td, 1 H, J ) 8.4, 3.5 Hz), 4.62 (s, 1 H), 7.34
(d, 2 H, J ) 8.1 Hz), 7.40-7.47 (m, 5 H), 7.59 (d, 2 H, J )
8.2 Hz). Data for 18g: mp 156-157 °C; Rf ) 0.15 (5%
oils. Data for 18a : Rf ) 0.31 (10% EtOAc-CH2Cl2); [R]20
)
D
1
+153.9 (c ) 0.80); H NMR (300 MHz) δ 0.89 (t, 3 H, J ) 7.2
Hz), 1.01 (t, 3 H, J ) 7.4 Hz), 1.32-1.50 (m, 4 H), 1.63-1.97
(m, 4 H), 2.38 (s, 4 H, OH), 3.58 (dd, 1 H, J ) 7.5, 4.0 Hz),
3.73 (dt, 1 H, J ) 8.8, 4.4 Hz), 7.26 (d, 2 H, J ) 8.2 Hz), 7.56
(d, 2 H, J ) 8.3 Hz); 13C NMR (50 MHz) δ 10.3, 13.8, 21.5,
22.3, 26.9, 27.9, 28.8, 61.4, 74.0, 81.1, 126.4 (2 C), 129.4 (2 C),
137.1, 142.0.
Syn th esis of (()-(1′S,2R,3S,SS)-3-P h en yl-2-(1′-h yd r oxy-
p r op yl)-2-(p-tolylsu lfin yl)oxir a n e, 15g. From t-BuOOH (25
µL, 18 mg, 0.20 mmol) in Et2O (1.25 mL), with n-BuLi (1.82
M, 0.14 mL, 0.25 mmol) and a solution of vinyl sulfoxide 3g
(19 mg, 0.063 mmol) in Et2O (0.50 mL), according to the
general procedure (0 °C, 5 h 45 min), was obtained a 92:8
mixture of epoxy sulfoxide 15g and epoxy sulfone 13g.
Purification by chromatography (0-15% EtOAc-CH2Cl2) gave
14 mg (70%) of 15g, as a white solid, recrystallized from 5%
EtOAc-hexane, and 4 mg (10%) of 13g.
1
EtOAc-CH2Cl2); H NMR (400 MHz) δ 0.97 (t, 3 H, J ) 7.4
Hz), 1.40-1.51 (m, 1 H), 1.80 (ddt, 1 H, J ) 14.3, 6.8, 4.2 Hz),
2.33 (s, 3 H), 4.31 (ap quint, J ) 4.2, 1 H), 4.43 (s, 1 H), 7.00
(d, 2 H, J ) 7.6 Hz), 7.17 (d, 2 H, J ) 7.9 Hz), 7.32-7.48 (m,
5 H); 13C NMR (50 MHz) δ 10.0, 21.4, 26.1, 60.0, 67.8, 82.8,
124.1 (2 C), 127.2 (2 C), 128.5 (2 C), 128.9, 130.1 (2 C), 132.5,
136.6, 142.0.
Gen er a l P r oced u r e for Oxid a tion w ith t-Bu OOH/VO-
(a ca c)2. To a solution of the sulfoxide in benzene (4 mL/mmol)
at room temperature was added VO(acac)2 (0.10 M solution
in benzene, or solid). After 5 min, a solution of t-BuOOH (5.5
M in decane), if necessary, further diluted in benzene to
measure accurately (0.5 mL/mmol) was added, and the mixture
turned reddish. Often, sequential additions of reagents were
needed to ensure completion of the reaction (TLC). The
reaction was then quenched with 1 M Na2S2O4 solution (4 mL/
mmol) and diluted with EtOAc (4 mL/mmol), and the aqueous
layer was extracted with EtOAc (two times, 4 mL/mmol). The
combined organic extracts were washed with saturated NaCl
(4 mL/mmol), dried over MgSO4, filtered, and concentrated
under reduced pressure to give a crude product that was
filtered through a plug of silica gel to remove the catalyst. After
monitoring by 1H NMR, the crude product was purified by
column chromatography on silica gel using the appropriate
mixture of solvents.
From NaH (6.1 mg, 0.25 mmol) in THF (1.0 mL), t-BuOOH
(36 µL, 26 mg, 0.28 mmol), and a solution of vinyl sulfoxide
3g (19 mg, 0.063 mmol) in THF (0.50 mL), according to the
general procedure (-30 °C, 4 h 30 min), was obtained epoxy
sulfoxide 15g. Purification by chromatography (0-20% Et2O-
CH2Cl2) gave 18 mg (90%) of 15g, as a white solid, recrystal-
lized from 5% EtOAc-hexane. Data for 15g: mp 120-121 °C;
Rf ) 0.33 (10% EtOAc-CH2Cl2); 1H NMR (300 MHz) δ 0.81 (t,
3 H, J ) 7.3 Hz), 1.06-1.14 (m, 1 H), 1.24-1.42 (m, 1 H), 2.34
(s, 3 H), 3.82 (m, 1 H), 4.28 (s, 1 H), 4.46 (ddd, 1 H, J ) 8.4,
4.4, 1.7 Hz), 6.88 (d, 2 H, J ) 8.3 Hz), 7.15 (d, 2 H, J ) 8.5
Hz), 7.39-7.46 (m, 5 H); 13C NMR (50 MHz) δ 9.6, 21.4, 25.1,
61.5, 67.8, 81.7, 124.4 (2 C), 127.2 (2 C), 128.6 (2 C), 129.2,
129.9 (2 C), 132.0, 135.8, 142.3.
Syn th esis of (()-(1′R,2S,3R,SS)-3-n -Bu tyl-2-(1′-h yd r oxy-
p r op yl)-2-(p -t olylsu lfin yl)oxir a n e, 17e, a n d (()-(1′R,2-
R,3S,SS)-3-n -Bu tyl-2-(1′-h ydr oxypr opyl)-2-(p-tolylsu lfin yl)-
oxir a n e, 18e. From KH (7 mg, 0.17 mmol) in THF (1.0 mL),
t-BuOOH (27 µL, 16 mg, 0.18 mmol), and a solution of vinyl
sulfoxide 4e (13 mg, 0.043 mmol) in THF (0.30 mL), according
to the general procedure (-10 to 0 °C, 3 h), a 52:48 mixture of
epoxy sulfoxides 17e and 18e was obtained. Purification by
chromatography (0-60% EtOAc-CH2Cl2) gave 6 mg (29%) of
17e, as a white solid, recrystallized from 5% EtOAc-hexane,
4 mg (19%) of 18e, as a colorless oil and 9 mg (45%) of starting
material.
Oxid a tion of (()-(1′R,2R,3S,SS)-3-P h en yl-(1′-h yd r oxy-
p r op yl)-2-(p-tolylsu lfin yl)oxir a n e, 18g. From epoxy sul-
foxide 18g (6 mg, 0.013 mmol) in benzene (0.70 mL), with
VO(acac)2 (1 mg, 0.004 mmol, 1 addition) and t-BuOOH (12
µL, 0.066 mmol), following the general procedure (14 h), was
obtained epoxy sulfone 14g (4 mg, 95%) after column chro-
matography (0-10% Et2O-CH2Cl2). Data for 14g: Rf ) 0.19
1
(5% EtOAc-CH2Cl2); H NMR (200 MHz) δ 1.02 (t, 3 H, J )
7.4 Hz), 1.59-1.80 (m, 2 H), 2.37 (s, 3 H), 2.99 (d, 1 H, J ) 5.9
Hz), 4.23 (dt, 1 H, J ) 9.0, 5.4 Hz), 4.36 (s, 1 H), 7.06-7.21
(m, 7 H), 7.32 (d, 2 H, J ) 8.6 Hz); 13C NMR (75 MHz) δ 10.4,
21.6, 25.0, 61.6 (C-1′), 73.1, 79.6, 126.6 (2 C), 127.9 (2 C), 128.0,
129.1 (2 C), 129.3 (2 C), 131.1, 134.0, 144.9.
From NaH (19 mg, 0.81 mmol) in THF (4.0 mL), t-BuOOH
(100 µL, 0.81 mmol), and a solution of vinyl sulfoxide 4e (57
mg, 0.203 mmol) in THF (1.50 mL), according to the general
procedure (-20 to 0 °C, 3 h), was obtained a 33:16:51 mixture
of epoxy sulfoxides 17e and 18e and starting material.
Purification by chromatography (0-10% EtOAc-CH2Cl2) gave
17 mg (27%) of 17e, 8 mg (13%) of 18e, and 24 mg (42%) of
starting material. Data for 17e: mp 72-73 °C; Rf ) 0.46 (10%
Syn th esis of (()-(Z)-2,2-Dim eth yl-4-n on en -3-ol, 19. To
a cold (-78 °C) solution of racemic vinyl sulfoxide 3c (41 mg,
0.13 mmol) in Et2O (1.5 mL) was added dropwise MeLi (0.88
M, 0.44 mL, 0.39 mmol) followed by t-BuLi (1.5 M, 0.34 mL,
0.51 mmol). After 10 min, the reaction was quenched with
MeOH (4 mL/mmol) and H2O (4 mL/mmol) and extracted with
EtOAc (three times, 5 mL/mmol), and the organic layer was
washed with a saturated solution of NaCl (4 mL/mmol), dried
over MgSO4, filtered, and concentrated under reduced pressure
to give a crude mixture that was purified by chromatography
(0-10% Et2O-CH2Cl2) to give 10 mg (45%) of allylic alcohol
19 and 13 mg of tert-butyl p-tolyl sulfoxide. Data for 19: Rf )
0.65 (10% EtOAc-CH2Cl2); 1H NMR (300 MHz) δ 0.88 (s, 9
H), 0.86-0.93 (m, 3 H), 1.23-1.36 (m, 4 H), 1.50 (br s, 1 H),
1.98-2.17 (m, 2 H), 4.06 (d, 1 H, J ) 9.2 Hz), 5.40 (ddt, 1 H,
J ) 11.0, 9.4, 1.6 Hz), 5.49-5.58 (m, 1 H); 13C NMR (50 MHz)
δ 14.1, 22.5, 25.6, 27.7, 29.0, 45.5, 75.0, 129.1, 133.8.
1
EtOAc-hexane); H NMR (300 MHz) δ 0.91 (t, 3 H, J ) 7.3
Hz), 0.97 (t, 3 H, J ) 7.2 Hz), 1.41-1.65 (m, 5 H), 1.73 (d, 1 H,
J ) 3.5 Hz), 1.88 (ddt, 1 H, J ) 14.0, 7.6, 3.2 Hz), 2.02-2.09
(m, 2 H), 2.41 (s, 3 H), 3.44 (t, 1 H, J ) 6.4 Hz), 3.78 (td, 1 H,
J ) 8.8, 3.3 Hz), 7.32 (d, 2 H, J ) 8.5 Hz), 7.56 (d, 2 H, J ) 8.4
Hz); 13C NMR (75 MHz) δ 9.8, 13.9, 21.4, 22.4, 27.2, 27.5, 28.5,
62.2, 68.0, 75.2, 125.0 (2 C), 129.8 (2 C), 136.2, 141.7. Data for
1
18e: Rf ) 0.22 (10% EtOAc-CH2Cl2); H NMR (300 MHz) δ
0.88 (t, 3 H, J ) 7.3 Hz), 0.94 (t, 3 H, J ) 7.2 Hz), 1.27-1.68
(m, 6 H), 1.88-1.97 (m, 2 H), 2.41 (s, 3 H), 3.34 (dd, 1 H, J )
8.1, 4.4 Hz), 4.04 (dd, 1 H, J ) 9.0, 4.3 Hz), 7.35 (d, 2 H, J )
7.9 Hz), 7.57 (d, 2 H, J ) 8.3 Hz); 13C NMR (75 MHz) δ 9.9,
13.9, 21.5, 22.3, 25.9, 28.6, 29.3, 61.2, 68.9, 80.5, 124.6 (2 C),
130.3 (2 C), 137.1, 142.0.
Syn th esis of (()-(1′R,2S,3R,SS)-3-P h en yl-2-(1′-h yd r oxy-
p r op yl)-2-(p-tolylsu lfin yl)oxir a n e, 17g, a n d (()-(1′R,2R,-
Syn th esis of (()-(1′S,2R,3R)-3-n -Bu tyl-2-(1′-h yd r oxy-
2′,2′-d im eth ylp r op yl)oxir a n e, 21. A round-bottomed flask
8176 J . Org. Chem., Vol. 67, No. 23, 2002

Epoxidation of R′-Hydroxy Vinyl Sulfoxides
was charged with anhydrous MeOH (1.0 mL), epoxy sulfone
13c (35 mg, 0.103 mmol), and Na2HPO4 (5.9 mg, 0.412 mmol),
and this mixture was cooled to 0 °C. Then, Na(Hg) (6%, 1300
mg) was added in small pieces, and the mixture was quenched
with a saturated solution of NH4Cl (4 mL/mmol) and H2O (4
mL/mmol). The crude mixture was extracted with EtOAc
(three times, 4 mL/mmol), and the organic extract was washed
with saturated solution of NaCl, dried over MgSO4, filtered,
and concentrated under reduced pressure to give a crude
product that was purified by column chromatography (0-15%
EtOAc-hexane), affording 8 mg (42%) of 21 and 12 mg (34%)
of starting material. Data for 21: Rf ) 0.10 (CH2Cl2). 1H NMR
(400 MHz) δ 0.89 (t, 3 H, J ) 7.9 Hz), 0.96 (s, 9 H), 1.34-1.44
(m, 4 H), 1.48-1.55 (m, 2 H), 1.93 (d, J ) 6.0 Hz), 2.82-2.85
(m, 1 H), 2.85-2.88 (m, 1 H), 3.06 (dd, 1 H, J ) 5.9, 5.0 Hz);
13C NMR (50 MHz) δ 13.9, 22.5, 25.8 (3 C), 28.1, 29.0, 34.7,
57.1, 58.5, 78.2.
8.4 Hz), 7.65 (d, 2 H, J ) 8.2 Hz), 7.72 (d, 2 H, J ) 8.9 Hz),
8.16 (d, 2 H, J ) 8.9 Hz); 13C NMR (50 MHz) δ 10.6, 14.6,
22.2, 23.1, 25.2, 25.9, 28.8, 62.1, 75.4, 77.5, 123.9 (2 C), 127.7
(2 C), 130.5 (2 C), 131.4 (2 C), 135.2, 138.0, 143.5, 148.6, 174.0.
Syn th esis of (()-(1′S,2S,3S)-3-P h en yl-2-(1′-h yd r oxyp r o-
p yl)oxir a n e, 23. To a cold (-78 °C) solution of epoxy sul-
foxide 15g (8 mg, 0.025 mmol) in THF (0.40 mL) was added
dropwise n-BuLi (1.8 M, 0.13 mL, 0.23 mmol), after stirring
during 55 min, the mixture was quenched with a saturated
solution of NH4Cl. The crude mixture was extracted with
EtOAc (three times, 4 mL/mmol), and the organic extract was
washed with saturated solution of NaCl, dried over MgSO4,
filtered, and concentrated under reduced pressure to give a
crude product that was purified by column chromatography
(0-30% EtOAc-hexane), affording 3 mg (68%) of 23 and 5 mg
of n-butyl p-tolyl sulfoxide. Data for 23: Rf ) 0.32 (30%
1
EtOAc-hexane); H NMR (200 MHz) δ 1.02 (t, 3 H, J ) 7.5
Syn th esis of th e p-Nitr oben zoa te of (+)-(1′R,2R,3R,SS)-
3-n -Bu t yl-2-(1′-h yd r oxyp r op yl)-2-(p -t olylsu lfin yl)ox-
ir a n e, 18a , 22. A round-bottomed flask was charged with THF
(0.6 mL), epoxy sulfoxide 18a (18 mg, 0.060 mmol), freshly
distilled Et3N (20 µL, 14.5 mg, 0.12 mmol), and two to three
crystals of DMAP, and the resulting mixture was cooled to 0
°C. After 10 min, p-nitrobenzoyl chloride (17 mg, 0.090 mmol)
was added, and after being stirred for 4 h, the reaction was
quenched with a saturated solution of NaHCO3 (4 mL/mmol).
The mixture was extracted with EtOAc (three times, 8 mL/
mmol), washed with a saturated solution of NaCl (4 mL/mmol),
dried over MgSO4, filtered, and concentrated under reduced
pressure to give a crude product that was purified by column
chromatography (5-30% EtOAc-hexane), affording 18 mg
(67%) of 22 as a white solid. Data for 22: mp 107-109 °C; Rf
Hz), 1.48-1.78 (m, 2 H), 1.93 (d, 1 H, J ) 2.2 Hz), 3.07 (t, 1 H,
J ) 2.6 Hz), 3.86-3.94 (m, 1 H), 3.95 (d, 1 H, J ) 2.0 Hz),
7.26-7.37 (m, 5 H).
Ack n ow led gm en t. This research was supported by
DGICYT (PPQ2000-1330 and BQV2001-0582) and CAM
(08.5/0079.1/2000). We thank J ANSSEN-CILAG for
additional support. We thank the MEC for a doctoral
fellowship to M.T. We are grateful to Professor S.
Valverde and Dr. J . C. Lo´pez (IQO, CSIC) for encour-
agement and support.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization for new compounds. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
) 0.20 (30% EtOAc-hexane); [R]20 ) +62.4 (c ) 0.60); 1H
D
NMR (200 MHz) δ 0.91 (t, 3 H, J ) 7.1 Hz), 0.93 (t, 3 H, J )
7.4 Hz), 1.32-2.15 (m, 8 H), 2.33 (s, 3 H), 3.67 (dd, 1 H, J )
7.8, 4.1 Hz), 5.34 (dd, 1 H, J ) 8.6, 6.2 Hz), 7.22 (d, 2 H, J )
J O026182S
J . Org. Chem, Vol. 67, No. 23, 2002 8177