Nucleophilic epoxidation of γ-hydroxyvinyl sulfoxide derivatives

Article abstract of DOI:10.1021/jo0342828

The nucleophilic epoxidation of simple (γ-silyloxy)vinyl sulfoxides takes place with complete stereocontrol and high yields. For substrates bearing an additional substituent at the γ position, a reinforcing/nonreinforcing scenario is operative. While E and Z silylated substrates undergo a primarily sulfur directed epoxidation with good to excellent diastereocontrol, the related (E)-(2-methoxyethoxy)methyl ethers display diminished selectivity for the diastereomer derived from the nonreinforcing scenario.

Full text of DOI:10.1021/jo0342828

Nu cleop h ilic Ep oxid a tion of γ-Hyd r oxyvin yl Su lfoxid e Der iva tives
Roberto Ferna´ndez de la Pradilla,*,† Mar´ıa Victoria Buergo,† Pilar Manzano,†
Carlos Montero,† J ulia´n Priego,† Alma Viso,† Fe´lix H. Cano,‡ and
Mar´ıa Paz Mart´ınez-Alca´zar§
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva 3, and Departamento de Cristalograf´ıa,
Instituto de Quı´mica-Fı´sica Rocasolano, CSIC, Serrano 119, 28006 Madrid,
and Departamento de Ciencias Ba´sicas, Facultad de Ciencias Experimentales y Te´cnicas,
Universidad San Pablo-CEU, Urbanizacio´n Monteprı´ncipe, Boadilla del Monte, 28668 Madrid, Spain
iqofp19@iqog.csic.es
Received March 4, 2003
The nucleophilic epoxidation of simple (γ-silyloxy)vinyl sulfoxides takes place with complete
stereocontrol and high yields. For substrates bearing an additional substituent at the γ position,
a reinforcing/nonreinforcing scenario is operative. While E and Z silylated substrates undergo a
primarily sulfur directed epoxidation with good to excellent diastereocontrol, the related (E)-(2-
methoxyethoxy)methyl ethers display diminished selectivity for the diastereomer derived from the
nonreinforcing scenario.
SCHEME 1
In tr od u ction
Sulfinyl- and sulfonyloxiranes are versatile function-
alities in organic synthesis.1 In many cases the synthetic
applications of these intermediates are limited by the lack
of general, short, and stereoselective routes to prepare
enantio- and diastereomerically pure substrates.2 For a
number of years we have been pursuing such a route, by
developing the nucleophilic epoxidation of readily avail-
able alkenyl sulfoxides with metalated peroxides.3,4 In
many cases, these epoxidations are exceptionally simple,
† Instituto de Qu´ımica Orga´nica, CSIC.
‡ Instituto de Qu´ımica-F´ısica Rocasolano, CSIC.
§ Universidad San Pablo-CEU.
(1) For
a review on the preparation and applications of R-oxy
stereoselective, and high yielding and thus should con-
stitute the method of choice to prepare a wide variety of
enantio- and diastereomerically pure sulfinyloxiranes
and, by a trivial oxidation, sulfonyloxiranes, as well.
sulfones, including sulfonyloxiranes, 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 sulfonyloxiranes, 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 sulfonyloxiranes, 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.
(2) A general approach to enantiopure sulfinyloxiranes relies on the
condensation between metalated R-chloro sulfoxides and aldehydes to
produce an almost equimolar mixture of two diastereomeric chloro-
hydrins due to low 1,3 asymmetric induction. Chromatographic separa-
tion followed by base-induced cyclization affords the desired epoxides:
(a) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J . Org. Chem. 1989,
54, 3130-3136. Alternatively, a vinyl sulfoxide has been treated with
aqueous N-bromosuccinimide to produce a mixture of bromohydrins
with good selectivity; after separation, the major diastereomer was
transformed into the corresponding epoxide as described above: (b)
Tsuchihashi, G.; Mitamura, S.; Ogura, K. Tetrahedron Lett. 1974, 455-
458.
In connection with these efforts we have also explored
the behavior of R′-(1-hydroxyalkyl)vinyl sulfoxides A
(Scheme 1) with mixed success,5 and we now report in
full our efforts on the epoxidation of protected γ-hydroxy-
vinyl sulfoxides C (Scheme 1).6 These studies are parallel
to the work of J ackson on related γ-hydroxyvinyl sul-
fones,7 as well as on diastereomeric (γ-alkoxyvinyl)-
sulfoximines,8 but we have also examined the behavior
of some Z substrates. These efforts have resulted in the
development of methodology for the preparation of a
variety of optically or diastereomerically pure γ-hydroxy
(3) For an expedient preparation of vinyl sulfoxides, see: Craig, D.;
Daniels, K.; McKenzie, A. R. Tetrahedron 1993, 49, 11263-11304.
(4) (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.
(5) (a) 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. (b) Ferna´ndez de la Pradilla, R.; Ferna´ndez, J .; Manzano,
P.; Me´ndez, P.; Priego, J .; Tortosa, M.; Viso, A.; Mart´ınez-Ripoll, M.;
Rodr´ıguez, A. J . Org. Chem. 2002, 67, 8166-8177.
(6) For a preliminary communication, see ref 5a.
(7) (a) J ackson, R. F. W.; Standen, S. P.; Clegg, W. Tetrahedron Lett.
1991, 32, 5393-5396. (b) J ackson, R. F. W.; Standen, S. P.; Clegg, W.
J . Chem. Soc., Perkin Trans. 1 1995, 149-156.
10.1021/jo0342828 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/16/2003
J . Org. Chem. 2003, 68, 4797-4805
4797

Ferna´ndez de la Pradilla et al.
SCHEME 2 a
SCHEME 3
to perform and would provide the same information on
the diastereoselectivity of the process. It should be
pointed out that these materials are also readily available
enantiomerically pure.10,11
a
Reagents and conditions: (a) (TBDMS)OTf, Et3N, DMAP,
THF, 0 °C to rt, 72% for 6b, 69% for 7b; (b) (MEM)Cl, i-Pr2EtN,
DMAP, CH2Cl2, rt, 48% for 6c, 60% for 7c.
To address the influence of the geometry of the
substrate on the nucleophilic epoxidation, we prepared
(Z)-(γ-silyloxy)vinyl sulfoxides 9 and 11 (Scheme 3) by
the procedure of Craig,3 using (2S)-2-[(tert-butyldiphe-
nylsilyl)oxy]propanal.12 As expected the corresponding E
isomers 8 and 10 were also produced under these
conditions. Finally, standard oxidation at sulfur of 9 gave
(Z)-vinyl sulfone 12 that was also needed to evaluate the
stereodirecting capabilities of the allylic silyloxy func-
tionality.
sulfinyl- and sulfonyloxiranes from readily available
alkenyl sulfoxides.
P r ep a r a tion of Su bstr a tes
The simplest (γ-silyloxy)vinyl sulfoxides 1 and 2
(Scheme 2) were prepared following the procedure of
Craig,3 using readily available 2-[(tert-butyldiphenylsilyl)-
oxy]acetaldehyde,9 in good yield and with fair selectivity.
The more substituted substrates 6 and 7 were prepared
by the protocol of Rayner,10 and at this stage we chose to
prepare racemic materials since it was somewhat easier
The structures of these substrates were assigned by
detailed inspection of their spectral features and by
(10) (a) Rayner, C. M.; Westwell, A. D. Tetrahedron Lett. 1992, 33,
2409-2412. (b) Westwell, A. D.; Rayner, C. M. Tetrahedron: Asym-
metry 1994, 5, 355-358. (c) Rayner, C. M.; Westwell, A. D.; Thornton-
Pett, M. J . Chem. Soc., Perkin Trans. 1 1995, 847-849.
(11) (a) Guerrero de la Rosa, V.; Ordo´n˜ez, M.; Alcudia, F.; Llera, J .
M. Tetrahedron Lett. 1995, 36, 4889-4892. (b) Guerrero de la Rosa,
V.; Ordo´n˜ez, M.; Llera, J . M. Tetrahedron: Asymmetry 2000, 11, 2991-
3001.
(12) (2S)-2-[(tert-Butyldiphenylsilyl)oxy]propanal was prepared in
75% overall yield in two steps from methyl lactate; see: (a) Gyoung,
Y. S.; Uyehara, T.; Yamamoto, Y. J . Org. Chem. 1997, 62, 6274-6282.
(b) Massad, S. K.; Hawkins, L. D.; Baker, D. C. J . Org. Chem. 1983,
48, 5180-5182.
(8) (a) 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. (b)
Briggs, A. D.; J ackson, R. F. W.; Brown, P. A. J . Chem. Soc., Perkin
Trans. 1 1998, 4097-4102.
(9) 2-[(tert-Butyldiphenylsilyl)oxy]acetaldehyde is available in two
steps from inexpensive 2-butene-1,4-diol [(TBDPS)Cl, imidazole, DMF;
O3, MeOH/CH2Cl2 and then Ph3P, 93% overall]; see: (a) Francesch,
A.; Alvarez, R.; Lo´pez, S.; de Lera, A. R. J . Org. Chem. 1997, 62, 310-
319. For alternative procedures, see: (b) J enn, T.; Heissler, D.
Tetrahedron 1998, 54, 107-118 (one-step protocol from commercially
available glycolaldehyde dimer). (c) Go¨rth, F. C.; Bru¨ckner, R. Synthesis
1999, 1520-1528 (two-step procedure from allyl alcohol).
4798 J . Org. Chem., Vol. 68, No. 12, 2003

Epoxidation of γ-Hydroxyvinyl Sulfoxide Derivatives
SCHEME 4
sulfoxides, and the results obtained are shown in Tables
1 and 2.
Our initial efforts were focused on alcohol (()-6a ,
which upon treatment with t-BuOONa at 0 °C (Table 1,
entry 1) led rapidly to complete dissappearance of start-
ing material but without formation of reasonable amounts
of the expected oxiranes. All efforts (entries 1 and 2) to
control this process were fruitless, with entry 3 affording
a substantial amount of recovered starting material with
just trace amounts of the desired oxiranes. We believe
that the reaction is indeed taking place but the resulting
hydroxy sulfinyloxiranes are unstable under these basic
conditions, presumably by undergoing a Payne rear-
rangement with loss of the sulfinyl moiety.16
In contrast, the epoxidation of silylated substrate (()-
6b took place smoothly to produce syn-oxirane (()-17b,
almost as a single isomer (Table 1, entry 4).17 The use of
t-BuOOLi gave rise to a 70:30 mixture of syn- and anti-
sulfonyloxiranes (()-19b and (()-20b in a very slow
reaction (entry 5). It is likely that in this case a pathway
involving oxidation to the vinyl sulfone followed by
epoxidation is operative. The (2-methoxyethoxy)methyl
(MEM)-protected substrate (()-6c gave a rather complex
mixture in a relatively slow reaction (entry 6) with an
estimated overall anti:syn selectivity of about 62:38. In
this case it appears that the sulfinyl group weakens the
anti-selective influence of the MEM protecting group (ca.
84:16 with t-BuOOLi for a related substrate) demon-
strated by J ackson. Finally, substrate 8 gave a very clean
reaction with exclusive syn selectivity (entry 7).
Table 2 shows our efforts on the epoxidation of the
(R,RS) diastereomers (()-7b and (()-7c. Entries 1 and 2
indicate that silylated substrate (()-7b gives rise to
oxiranes with good anti selectivity, but the temperature
has to be strictly controlled particularly at the early
stages of the reaction to prevent overoxidation to the
sulfonyloxirane. On the other hand, MEM-protected
substrate (()-7c gave a totally anti selective epoxidation
with a small amount of overoxidation (entry 3), with the
sulfinyl group enhancing the effect of the MEM group.
known chemical transformations in the case of (()-4 and
(()-5.13
Ep oxid a tion of 1 a n d 2
Our initial efforts were directed to study the epoxida-
tion of the simple, unsubstituted (silyloxy)alkenyl sul-
foxides 1 and 2 (Scheme 4). The behavior of Z substrate
2 was of particular interest to us since, if highly selective,
it would constitute an extremely short route to a valuable
building block, a close analogue (p-tolyl vs phenyl) of an
epoxy sulfone used in Mori’s Hemibrevetoxin synthesis.14
In the event, E substrate 1 was unreactive to t-
BuOONa but gave a fair unoptimized yield of epoxy
sulfoxide 13 as a single diastereomer with t-BuOOK. In
contrast, the treatment of 2 with t-BuOONa in THF gave
a rapid and clean reaction to produce sulfinyloxirane 15
as a single isomer and in high yield. Standard oxidation
of 13 and 15 gave sulfonyloxiranes 14 and 16, respec-
tively. In this manner, cis-sulfonyloxirane 16 is now
readily available (20-35% unoptimized overall yield in
4-5 steps in this work vs ca. 5% in 10 linear steps from
gulonolactone in Mori’s procedure).15
Ep oxid a tion of (Z)-γ-Hyd r oxyvin yl Su lfoxid e
Der iva tives
At the beginning of this part of the study, to our
knowledge, there was a single literature precedent of a
nucleophilic epoxidation of an enantiopure (Z)-γ-alkoxy-
vinyl sulfone (Scheme 5), studied by Mori, as a key
step in his synthesis of an intermediate related to 16.15
The complete preservation of geometry found by Mori for
the epoxidation with t-BuOOK is noteworthy and in
sharp contrast with previous knowledge in the litera-
ture.18
Prior to studying the behavior of the (Z)-sulfoxides, we
examined the epoxidation of (Z)-sulfone 12, and the
results obtained are shown in Table 3. The use of
t-BuOOLi gave a relatively low conversion with low anti
selectivity (23:24 ) 34:14) along with trace amounts of
Ep oxid a tion of (E)-γ-Hyd r oxyvin yl Su lfoxid e
Der iva tives
J ackson has studied the nucleophilic epoxidation of a
variety of γ-hydroxyvinyl sulfones with regard to the size
of the allylic substituent R, the influence of the protecting
group on the hydroxyl group, and the use of Li or K as
counterion.7 In view of these results we designed a short
study directed to evaluate the viability and stereoselec-
tivity of this process for diastereomeric γ-hydroxyalkenyl
(13) All new products have been fully characterized by spectroscopic
techniques. See the Supporting Information.
(14) (a) Mori, Y.; Yaegashi, K.; Furukawa, H. J . Am. Chem. Soc.
1996, 118, 8158-8159. (b) Mori, Y.; Yaegashi, K.; Furukawa, H. J .
Am. Chem. Soc. 1997, 119, 4557-4558. (c) For a recent application of
this building block within synthetic studies toward Yessotoxin and
Adriatoxin, see: Mori, Y.; Takase, T.; Noyori, R. Tetrahedron Lett.
2003, 44, 2319-2322.
(16) Payne, G. B. J . Org. Chem. 1962, 27, 3819-3822.
(17) 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.
(18) Meth-Cohn, O.; Moore, C.; Taljaard, H. C. J . Chem. Soc., Perkin
Trans. 1 1988, 2663-2674.
(15) Mori, Y.; Yaegashi, K.; Furukawa, H. Tetrahedron 1997, 53,
12917-12932.
J . Org. Chem, Vol. 68, No. 12, 2003 4799

Ferna´ndez de la Pradilla et al.
TABLE 1. Ep oxid a tion of (S,RS)-(E)-γ-Hyd r oxyvin yl Su lfoxid e Der iva tives
yielda
entry
substrate
conditions
A
B
C
D
(%)
1b
2
(()-6a
(()-6a
(()-6a
(()-6b
(()-6b
(()-6c
8
M ) Na, 0 °C, 15 min
M ) Na, -78 to -20 °C, 5 h
M ) Li, -78 to rt, 150 min
M ) Na, -20 °C, 20 h
3c
4
(()-17b (97)
(()-18b (3)
(()-18c (51)
80
81
95
82
5d
6
7
M ) Li, -20 °C to rt, 4 days
M ) Na, 0 °C, 70 min
M ) Na, 0 °C, 330 min
(()-19b (70)
(()-19c (2)
19d (9)
(()-20b (30)
(()-20c (11)
(()-17c (36)
17d (91)
a
b
Yields of pure products after column chromatography. Starting material rapidly disappeared, leading to a complex reaction mixture
with low material balance. c Approximately 50% starting material recovered with the remainder being a complex mixture with low material
d
balance. Reaction carried out in Et2O.
TABLE 2. Ep oxid a tion of (R,RS)-(E)-γ-Hyd r oxyvin yl Su lfoxid e Der iva tives
yielda
entry
substrate
conditions
A
B
C
D
(%)
1b
2
3
(()-7b
(()-7b
(()-7c
M ) Na, 0 °C, 4 h
M ) Na, -20 to 0 °C, 4 h
M ) Na, 0 °C, 90 min
(()-21b (9)
(()-21b (11)
(()-22b (75)
(()-22b (89)
(()-22c (93)
(()-ent-20b (16)
78
78
77
(()-ent-20c (7)
a
b
Yields of pure products after column chromatography. While these products are racemic, the ent nomenclature is used to facilitate
the understanding of the stereochemical relationships.
SCHEME 5
The data gathered in Table 4 illustrate the behavior
of diastereomeric sulfoxides 9 and 11. The epoxidation
of 9 with t-BuOONa takes place smoothly to produce anti-
sulfinyloxirane 25 in a highly stereoselective manner
(entry 1). The use of t-BuOOK gave comparable results
but with a small amount of anti-sulfonyloxirane derived
from overoxidation (entry 2). In contrast, diastereomer
11 was unreactive to t-BuOONa (entry 3), and gave a
slow, but highly selective syn epoxidation with t-BuOOK
(entry 4). These results may be accounted for in terms of
the sulfur atom being the predominant element of ste-
reocontrol within a reinforcing/nonreinforcing scenario.
The complete retention of E/Z geometry found for these
sulfoxides, relative to the related sulfone 12, is notewor-
thy.
trans-sulfonyloxiranes 20d and 19d (entry 1). The more
reactive t-BuOONa (entry 2) gave a more complex
mixture of cis- and trans-oxiranes, substantially enriched
in the trans isomers, with an estimated overall anti:syn
ratio of 60:40. Finally, the use of t-BuOOK gave almost
complete conversion, in a similar anti:syn ratio, and with
predominant formation of the trans-oxiranes (entry 3).
In conclusion, the γ-silyloxy substituent appears to favor
a moderately anti selective process for this substrate but
with loss of geometric selectivity when sodium or potas-
sium tert-butyl peroxides are used.
Ch em ica l Cor r ela tion s
Scheme 6 shows the oxidations carried out to correlate
the structures of trans-epoxy sulfoxides and -epoxy
sulfones to the known syn- and anti-sulfonyloxiranes (()-
19c and (()-20c. On the other hand, a firm assignment
for the TBDMS series was obtained by desilylation of a
4800 J . Org. Chem., Vol. 68, No. 12, 2003

Epoxidation of γ-Hydroxyvinyl Sulfoxide Derivatives
TABLE 3. Ep oxid a tion of (Z)-γ-Alk oxyvin yl Su lfon e 12
yielda
(%)
entry
conditions
SM
A
B
C
D
1
2
3
M ) Li, 0 °C to rt, 24 h
M ) Na, -30 °C to rt, 4 h and 15 min
M ) K, -30 °C to rt, 2 h and 15 min
12 (48)
12 (20)
12 (6)
23 (34)
23 (21)
23 (15)
24 (14)
24 (11)
24 (7)
20d (2)
20d (27)
20d (41)
19d (2)
19d (21)
19d (31)
84
79
80
a
Yields of pure products after column chromatography, including starting material.
TABLE 4. Ep oxid a tion of (Z)-γ-Alk oxyvin yl Su lfoxid es
yielda
(%)
entry
substrate
conditions
SM
25
25
25 (90)
23
26
24
1
2
3
4
9
9
11
11
M ) Na, 0 °C, 15 h
M ) K, 0 °C, 23 h
M ) Na, 0 °C, 15 h
M ) K, 0 °C, 87 h
88
90
23 (10)
11 (100)
11 (6)
26 (73)
24 (21)
72
a
Yields of pure products after column chromatography, including starting material.
mixture of (()-19b and (()-20b to produce the known
hydroxy sulfonyloxiranes (()-19a and (()-20a .
Finally, Scheme 7 shows the oxidations of cis-sulfiny-
loxiranes 25 and 26 to produce diastereomeric sulfony-
loxiranes 23 and 24. It should be mentioned that the
structure of 25 was secured by an X-ray diffraction
analysis.19
finyl oxygen, to produce the syn-sulfinyloxirane with
very high selectivity. On the other hand, diastereomer 7
would follow reactive conformer B with predominant
sulfur-directed attack to produce the anti isomer. Alter-
natively, these reactions could take place by chair-
like reactive conformers A′ and B′ that involve as-
sociation of the sulfinyl oxygen to the metal and with
the bulky arylsulfinyl group in an equatorial arrange-
ment.23
Resu lts a n d Discu ssion
Scheme 9 gathers our rationalization of the results
found for the epoxidation of the Z substrates. In our
hands, sulfone 12 (reactive conformer C) gave low overall
R:â selectivity and substantial loss of geometric integrity
to produce 23 along with the E isomers (see Table 3). In
contrast, reinforcing diastereomer 9 gave a totally ste-
reoselective reaction, affording 25 as a single isomer with
complete control of both the syn:anti and the geometric
selectivities even with t-BuOONa. Furthermore, nonre-
inforcing diastereomer 11 gave 26 as a single isomer
The selectivity of the epoxidation of the E substrates
may be accounted for by considering a reinforcing/
nonreinforcing scenario,20 as shown in Scheme 8. We
propose an s-cis arrangement for the alkene and the lone
pair on sulfur, which has been shown to be the most
stable conformer for cis-vinyl sulfoxides and to have a
very small energy difference compared to the s-cis oxygen/
alkene conformer for E substrates.21 As suggested by
J ackson,7 for relatively small R groups, reactive con-
former A, which places the Pr group at the inside
position,22 is operative with the incoming nucleophile
attacking anti to the silyloxy group and syn to the sul-
(22) With regard to the conformation of the allylic center, Gung has
shown that tert-butyldimethylsilyl ethers enhance the preference for
the CO-eclipsed form for (E)-γ-hydroxy-R,â-unsaturated esters, and
related reactive conformers have been proposed by Yamamoto as
transition-state models for conjugate additions of cuprates; our results
cannot be readily accounted for by these models. See: (a) Gung, B.
W.; Wolf, M. A.; Zhu, Z. J . Org. Chem. 1993, 58, 3350-3354. (b) Gung,
B. W.; Wolf, M. A. J . Org. Chem. 1993, 58, 7038-7044. (c) Gung, B.
W.; Melnick, J . P.; Wolf, M. A.; King, A. J . Org. Chem. 1995, 60, 1947-
1951. (d) Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.; Kitahara,
H. J . Am. Chem. Soc. 1992, 114, 7652-7660.
(19) We have deposited atomic coordinates for this structure with
the Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Rd., Cambridge CB2 1EZ, U.K. (CCDC 205606).
(20) Evans, D. A.; Dart, M. J .; Duffy, J . L.; Yang, M. G. J . Am. Chem.
Soc. 1996, 118, 4322-4343.
(21) For a computational treatment of the conformations of R,â-
unsaturated sulfoxides, see: Tiezte, L. F.; Schuffenhauer, A.; Schreiner,
P. R. J . Am. Chem. Soc. 1998, 120, 7952-7958 and references therein.
(23) We thank one of the reviewers for suggesting this rationaliza-
tion.
J . Org. Chem, Vol. 68, No. 12, 2003 4801

Ferna´ndez de la Pradilla et al.
SCHEME 6
SCHEME 8
SCHEME 9
SCHEME 7
Con clu sion s
along with some product of overoxidation in a completely
sulfur directed process that required the use of the more
reactive t-BuOOK. Alternatively, chairlike reactive con-
formers D′ and E′ could be operative.23
The nucleophilic epoxidation of R-unsubstituted (E)-
and (Z)-(γ-silyloxy)vinyl sulfoxides takes place with high
levels of diastereoselectivity with the chiral sulfur being
4802 J . Org. Chem., Vol. 68, No. 12, 2003

Epoxidation of γ-Hydroxyvinyl Sulfoxide Derivatives
Syn th esis of th e ter t-Bu tyld im eth ylsilyl Eth er of (()-
(E)-(3S,RS)-1-(P h en ylsu lfin yl)-1-h exen -3-ol, (()-6b. From
vinyl sulfoxide (()-6a (60 mg, 0.27 mmol) in THF (2.0 mL),
with Et3N (75 µL, 55 mg, 0.54 mmol) and TBDMSOTf (124
µL, 142.7 mg, 0.54 mmol), according to the general procedure
(2 h), after chromatography (5-30% EtOAc-hexane), pro-
tected alcohol (()-6b (65 mg, 72%) was obtained as a colorless
oil: Rf ) 0.13 (2% EtOAc-hexane); 1H NMR (300 MHz) δ
-0.09 (s, 3 H), -0.02 (s, 3 H), 0.81 (s, 9 H), 0.87 (t, 3 H, J )
7.3 Hz), 1.29-1.36 (m, 2 H), 1.46-1.52 (m, 2 H), 4.30 (ap qd,
1 H, J ) 4.6, 1.5 Hz), 6.36 (dd, 1 H, J ) 14.9, 1.5 Hz), 6.58
(dd, 1 H, J ) 14.9, 4.5 Hz), 7.44-7.50 (m, 3 H), 7.51-7.60 (m,
2 H); 13C NMR (50 MHz) δ -5.0, -4.7 (2 C), 14.0, 18.2, 25.7 (3
C), 39.6, 71.4, 124.5 (2 C), 129.3 (2 C), 131.0, 133.8, 141.9,
144.0.
the main element of stereocontrol. In addition, an expedi-
ent route to a valuable building block for the synthesis
of complex tetrahydropyrans has been outlined.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of (γ-Silyloxy)-
vin yl Su lfoxid es. Under an argon atmosphere a round-
bottomed flask was charged with THF (3.5 mL/mmol) and 4
equiv of (MeO)2POMe (redistilled from CaH2) and cooled to
-78 °C. To the above solution was added 3.9 equiv of n-BuLi,
and the mixture was stirred at -78 °C for 10 min, after which
time a solution of 2 equiv of (1R,2S,5R)-(-)-menthyl (S)-p-
toluenesulfinate (dried azeotropically with C6H6 prior to use),
in THF (0.75 mL/mmol of sulfinate), was added dropwise via
syringe. The reaction mixture was stirred at -78 °C for 10
min (in some cases the cooling bath was removed for 10-15
min to speed up the consumption of the sulfinate), and then a
solution of 1 equiv of aldehyde in THF (3 mL/mmol) was added
dropwise. The mixture was stirred at -78 °C until starting
material disappearance, monitored by TLC (ca. 15 min). The
reaction was quenched with a saturated solution of NH4Cl (1
mL/mmol) and H2O (1 mL/mmol) and diluted with EtOAc (4
mL/mmol), and the layers were separated. The aqueous layer
was extracted twice with EtOAc (1 mL/mmol), and the
combined organic extracts were dried over MgSO4 and con-
centrated under reduced pressure to give a crude product that
was purified by column chromatography on silica gel.
Syn th esis of th e (+)-ter t-Bu tyld ip h en ylsilyl Eth er of
(E)-(2S,RS)-4-(p-Tolylsu lfin yl)-3-bu ten -2-ol, 8, a n d (-)-
ter t-Bu tyld ip h en ylsilyl Eth er of (Z)-(2S,RS)-4-(p-Tolyl-
su lfin yl)-3-bu ten -2-ol, 9. From (MeO)2POMe (0.15 mL, 170
mg, 1.32 mmol) in THF (2.1 mL), n-BuLi (0.88 mL, 1.5 M, 1.29
mmol), (-)-menthyl sulfinate (195.4 mg, 0.66 mmol), and a
solution of (2S)-2-[(tert-butyldiphenylsilyl)oxy]propanal (103.7
mg, 0.33 mmol) in THF (0.82 mL) according to the general
procedure (1 h), a 27:73 mixture of vinyl sulfoxides 8 and 9
was obtained. Purification by chromatography (5-30% EtOAc-
hexane and then toluene-20% EtOAc-toluene) gave 54 mg
(36%) of (Z)-sulfoxide 9 and 14 mg (14%) of E isomer 8, both
Gen er a l P r oced u r e for P r otection of Su lfin yl Alcoh ols
w ith (MEM)Cl. Under an atmosphere of argon, 8.0 equiv of
(2-methoxyethoxy)methyl chloride [(MEM)Cl] was added to a
cold (0 °C) solution of the sulfinyl alcohol, 8 equiv of N,N-
diisopropylethylamine, and 0.8 equiv of DMAP in CH2Cl2 (10
mL/mmol), and the reaction mixture was allowed to warm to
rt and monitored by TLC. Upon completion the reaction was
quenched with H2O (1 mL/mmol) and diluted with CH2Cl2 (8
mL/mmol), and the layers were separated. The aqueous phase
was extracted with CH2Cl2 (three times, 10 mL/mmol), and
the combined organic extracts were 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 on silica gel
using a gradient of the appropriate solvents.
Syn th esis of th e (2-Meth oxyeth oxy)m eth yl Eth er of
(()-(E)-(3R,RS)-1-(P h en ylsu lfin yl)-1-h exen -3-ol, (()-7c.
From vinyl sulfoxide (()-7a (21.9 mg, 0.10 mmol) in CH2Cl2
(0.90 mL), with (i-Pr)2EtN (136 µL, 101.3 mg, 0.78 mmol),
DMAP (9.6 mg, 0.078 mmol), and (MEM)Cl (105 µL, 97.6 mg,
0.78 mmol), according to the general procedure (23 h), after
chromatography (5-40% EtOAc-CH2Cl2 and then 10-50%
EtOAc-hexane), protected alcohol (()-7c (18.2 mg, 60%) was
obtained as a colorless oil: Rf ) 0.47 (40% EtOAc-CH2Cl2);
1H NMR (300 MHz) δ 0.89 (t, 3 H, J ) 7.2 Hz), 1.23-1.60 (m,
4 H), 3.37 (s, 3 H), 3.45-3.71 (m, 4 H), 4.25 (q, 1 H, J ) 6.1
Hz), 4.64 (s, 2 H), 6.39 (dd, 1 H, J ) 15.1, 0.7 Hz), 6.50 (dd, 1
H, J ) 15.1, 5.9 Hz), 7.46-7.50 (m, 3 H), 7.57-7.60 (m, 2 H);
13C NMR (50 MHz) δ 13.8, 18.3, 37.1, 59.0, 67.1, 71.6, 71.7,
75.1, 124.5 (2 C), 129.4 (2 C), 131.1, 136.0, 138.7, 143.9.
as colorless oils. Data for 8: Rf ) 0.31 (30% EtOAc-hexane);
1
[R]20 ) +3.5 (c ) 0.75); H NMR (300 MHz) δ 1.00 (s, 9 H),
D
1.15 (d, 3 H, J ) 6.5 Hz), 2.41 (s, 3 H), 4.45 (m, 1 H), 6.37 (dd,
1 H, J ) 15.0, 1.5 Hz), 6.54 (dd, 1 H, J ) 14.9, 4.3 Hz), 7.14-
7.50 (m, 10 H), 7.50-7.60 (m, 4 H); 13C NMR (50 MHz) δ 19.2,
21.4, 23.4, 26.9 (3 C), 68.7, 124.8 (2 C), 125.3, 127.6 (4 C), 128.2,
129.0, 129.7 (2 C), 130.0 (2 C), 133.7, 135.7 (2 C), 135.8 (2 C),
141.0, 141.5, 142.0. Data for 9: Rf ) 0.22 (30% EtOAc-
hexane); [R]20D ) -114.6 (c ) 0.81); 1H NMR (300 MHz) δ 1.05
(s, 9 H), 1.37 (d, 3 H, J ) 6.3 Hz), 2.37 (s, 3 H), 5.20 (dqd, 1 H,
J ) 8.2, 6.3, 1.1 Hz), 5.99 (dd, 1 H, J ) 9.9, 1.1 Hz), 6.27 (dd,
1 H, J ) 9.9, 8.2 Hz), 7.15 (br s, 4 H), 7.30-7.46 (m, 6 H),
7.61-7.70 (m, 4 H); 13C NMR (75 MHz) δ 19.1, 21.3, 24.8, 26.8
(3 C), 66.7, 124.0 (2 C), 127.6 (2 C), 127.7 (2 C), 129.7 (2 C),
129.8 (2 C), 129.9 (2 C), 133.3, 133.6, 133.9, 135.7 (2 C), 140.8,
141.0, 145.5.
Gen er a l P r oced u r e for Oxid a tion of Su lfoxid es w ith
Magn esiu m Mon oper oxyph th alate Hexah ydr ate (MMP P ).
To a cold (0 °C) solution of sulfoxide in MeOH (10 mL/mmol)
was added 1.5-3.0 equiv of MMPP. The mixture was stirred
from 0 °C to rt, 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 sepa-
rated, 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 th e ter t-Bu tyld ip h en ylsilyl Eth er of (Z)-
(2S)-4-(p-Tolylsu lfon yl)-3-bu ten -2-ol, 12. From sulfinylox-
irane 9 (75.6 mg, 0.168 mmol) in MeOH (1.68 mL) and MMPP
(312.5 mg, 0.50 mmol), according to the general procedure (4
h 30 min), after chromatography (5-30% EtOAc-hexane),
vinyl sulfone 12 (75.7 mg, 97%) was obtained as a colorless
oil: Rf ) 0.50 (30% EtOAc-hexane); 1H NMR (300 MHz) δ
1.01 (s, 9 H), 1.30 (d, 3 H, J ) 6.3 Hz), 2.38 (s, 3 H), 5.54 (m,
1 H), 5.95 (dd, 1 H, J ) 11.4, 1.4 Hz), 6.27 (dd, 1 H, J ) 11.4,
7.8 Hz), 7.14 (d, 2 H, J ) 8.5 Hz), 7.28 (d, 2 H, J ) 7.0 Hz),
7.34-7.46 (m, 6 H), 7.52 (d, 2 H, J ) 8.1 Hz), 7.63 (d, 2 H, J
) 8.1 Hz); 13C NMR (50 MHz) δ 19.0, 21.6, 24.3, 26.8 (3 C),
Gen er a l P r oced u r e for Silyla tion of Su lfin yl Alcoh ols.
Under an atmosphere of argon, 2.0 equiv of freshly distilled
tert-butyldimethylsilyl triflate was added to a cold (0 °C)
solution of the sulfinyl alcohol, 2.5 equiv of Et3N, and 2-3
crystals of DMAP in THF (10 mL/mmol), and the reaction
mixture was allowed to warm to rt and monitored by TLC.
Upon completion 2 equiv of Et3N was added, the reaction was
quenched with a saturated solution of NaHCO3 (4 mL/ mmol)
and diluted with EtOAc (8 mL/mmol), and the layers were
separated. The aqueous phase was extracted with EtOAc
(three times), and the combined organic extracts were 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 chroma-
tography on silica gel using a gradient of the appropriate
solvents.
J . Org. Chem, Vol. 68, No. 12, 2003 4803

Ferna´ndez de la Pradilla et al.
65.4, 127.0, 127.3 (2 C), 127.5 (2 C), 127.6 (2 C), 129.6, 129.7
(2 C), 133.7, 135.6 (2 C), 135.7 (2 C), 137.9, 138.0, 144.2, 149.6.
(s, 3 H), 0.78 (s, 9 H), 0.83 (t, 3 H, J ) 7.2 Hz), 1.20-1.35 (m,
4 H), 3.55 (dd, 1 H, J ) 2.8, 1.8 Hz), 3.87 (td, 1 H, J ) 5.4, 2.8
Hz), 3.90 (d, 1 H, J ) 1.7 Hz), 7.52-7.55 (m, 3 H), 7.62-7.66
(m, 2 H).
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 ) With LiOO-t-Bu . A two-necked round-
bottomed flask fitted with a tube in T formation 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), 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 constant temperature until starting material disappearance,
monitored by TLC. The reaction was then quenched with a
10% solution of Na2S2O4 (4 mL/mmol) and diluted whith EtOAc
(8 mL/mmol), and the layers were separated. The aqueous
layer was extracted with EtOAc (three times, 10 mL/mmol),
Syn th esis of (()-(2R,3R,1′R,SS)-3-[1′-[(Meth oxyeth oxy)-
m eth oxy]-n -bu tyl]-2-(ph en ylsu lfin yl)oxir an e, (()-22c, an d
(()-(2R,3R,1′R)-3-[1′-[(Meth oxyeth oxy)m eth oxy]-n -bu tyl]-
2-(p h en ylsu lfon yl)oxir a n e, (()-en t-20c. From NaH (4 mg,
0.18 mmol) in THF (0.90 mL), t-BuOOH (22 µL, 20 mg, 0.17
mmol), and a solution of vinyl sulfoxide (()-7c (14 mg, 0.04
mmol) in THF (0.30 mL), according to the general procedure
(1 h 30 min), a 93:7 mixture of sulfinyloxirane (()-22c and
sulfonyloxirane (()-ent-20c was obtained. Purification by
chromatography (5-40% EtOAc-CH2Cl2) gave 11.1 mg (77%)
of (()-22c as a colorless oil and traces of (()-ent-20c. Data for
(()-22c: Rf ) 0.44 (40% EtOAc-CH2Cl2); 1H NMR (300 MHz)
δ 0.89 (t, 3 H, J ) 7.1 Hz), 1.21-1.57 (m, 4 H), 3.35 (s, 3 H),
3.39 (dd, 1 H, J ) 4.6, 1.8 Hz), 3.49-3.65 (m, 5 H), 4.07 (dd,
1 H, J ) 1.9, 0.4 Hz), 4.59 (d, 1 H, J ) 7.2 Hz), 4.64 (d, 1 H,
J ) 7.2 Hz), 7.50-7.55 (m, 3 H), 7.63-7.68 (m, 2 H); 13C NMR
(75 MHz) δ 14.0, 18.1 (2 C), 34.8, 57.5, 59.0, 67.3, 70.7, 71.6,
74.0, 95.3, 124.8 (2 C), 129.4 (2 C), 131.7. The data for (()-
ent-20c were identical to those found later.
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 chroma-
tography on silica gel, using a gradient of mixtures of EtOAc-
hexane or EtOAc-CH2Cl2. Product ratios were determined by
integration of well-resolved signals in the 1H NMR of the crude
reaction mixtures.
(b) With Na OO-t-Bu or KOO-t-Bu . A two-necked round-
bottomed flask fitted with a tube in T formation 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 (washed with hexane and dried), 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 rt 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 (7 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 (+)-(2R,3S,1′S,SS)-3-[1′-[(ter t-Bu tyld ip h e-
n ylsilyl)oxy]eth yl]-2-(p-tolylsu lfin yl)oxir a n e, 25, a n d (+)-
(2R,3S,1′S)-3-[1′-[(ter t-Bu tyld ip h en ylsilyl)oxy]eth yl]-2-(p-
tolylsu lfon yl)oxir a n e, 23. From NaH (12.0 mg, 0.52 mmol)
in THF (2.60 mL), t-BuOOH (65 µL, 59 mg, 0.52 mmol), and
a solution of vinyl sulfoxide 9 (58.4 mg, 0.13 mmol) in THF
(0.90 mL), according to the general procedure (0 °C, 15 h),
sulfinyloxirane 25 was obtained. Purification by chromatog-
raphy (5-30% EtOAc-hexane) gave 52.9 mg (88%) of 23 as a
white solid recrystallized from Et2O-hexane. From KH (11.6
mg, 0.29 mmol) in THF (1.40 mL), t-BuOOH (36 µL, 33 mg,
0.29 mmol), and a solution of vinyl sulfoxide 9 (32.6 mg, 0.072
mmol) in THF (0.50 mL), according to the general procedure
(0 °C, 23 h), a 90:10 mixture of sulfinyloxirane 25 and
sulfonyloxirane 23 was obtained. Purification by chromatog-
raphy (5-30% EtOAc-hexane) gave 5.6 mg (16%) of 23 as a
colorless oil and 24.7 mg (74%) of 25 as a white solid. Data for
Syn th esis of (-)-(Z)-(2R,3S,SS)-3-[1′-[(ter t-Bu tyld ip h e-
n ylsilyl)oxy]m eth yl]-2-(p-tolylsu lfin yl)oxir a n e, 15. From
NaH (9 mg, 0.37 mmol) in THF (1.85 mL), t-BuOOH (46 µL,
42 mg, 0.37 mmol), and a solution of vinyl sulfoxide 2 (40.4
mg, 0.09 mmol) in THF (0.65 mL), according to the general
procedure (20 min), sulfinyloxirane 15 was obtained. Purifica-
tion by chromatography (5-30% EtOAc-hexane) gave 33.4 mg
25: mp 95-99 °C; Rf ) 0.34 (30% EtOAc-hexane); [R]20
)
D
1
+29.4 (c ) 0.70); H NMR (300 MHz) δ 1.07 (s, 9 H), 1.19 (d,
3 H, J ) 6.2 Hz), 2.38 (s, 3 H), 3.23 (dd, 1 H, J ) 6.2, 3.5 Hz),
3.80 (d, 1 H, J ) 3.5 Hz), 4.41 (quint, 1 H, J ) 6.2 Hz), 7.23
(d, 2 H, J ) 8.5 Hz), 7.34-7.50 (m, 8 H), 7.70 (d, 4 H, J ) 8.0
Hz); 13C NMR (75 MHz) δ 19.2, 21.4 (2 C), 26.9 (3 C), 62.5,
66.1, 74.4, 124.8 (2 C), 127.7 (4 C), 129.8, 129,9, 130.0 (2 C),
133.5, 133.7, 135.8 (2 C), 138.2, 142.1. The data for 23 were
identical to those found later.
(90%) of 15, as a colorless oil: Rf ) 0.27 (30% EtOAc-hexane);
1
[R]20 ) -8.1 (c ) 0.48); H NMR (300 MHz) δ 1.08 (s, 9 H),
D
2.40 (s, 3 H), 3.36 (td, 1 H, J ) 5.2, 3.8 Hz), 3.94 (d, 1 H, J )
3.8 Hz), 4.02 (dd, 1 H, J ) 11.8, 5.2 Hz), 4.10 (dd, J ) 12.0,
5.5 Hz), 7.28-7.31 (m, 2 H), 7.36-7.47 (m, 6 H), 7.59 (d, 2 H,
J ) 8.3 Hz), 7.65-7.68 (m, 4 H); 13C NMR (50 MHz) δ 19.2,
21.5, 26.8 (3 C), 57.9, 61.7, 74.8, 124.5 (2 C), 127.9 (4 C), 130.1,
130.2 (2 C), 132.5, 135.5 (4 C), 137.6, 142.2.
Syn th esis of (-)-(2S,3R,1′S,RS)-3-[1′-[(ter t-Bu tyld ip h e-
n ylsilyl)oxy]eth yl]-2-(p-tolylsu lfin yl)oxir a n e, 26, a n d (-)-
(2S,3R,1′S)-3-[1′-[(ter t-Bu tyld ip h en ylsilyl)oxy]eth yl]-2-(p-
tolylsu lfon yl)oxir a n e, 24. From KH (8.7 mg, 0.21 mmol) in
THF (1.0 mL), t-BuOOH (27 µL, 34 mg, 0.21 mmol), and a
solution of vinyl sulfoxide 11 (24.4 mg, 0.054 mmol) in THF
(0.37 mL), according to the general procedure (0 °C, 87 h), a
6:73:21 mixture of starting material, sulfinyloxirane 26, and
sulfonyloxirane 24 was obtained. Purification by chromatog-
raphy (1-5% EtOAc-CH2Cl2) gave 21 mg (62%) of 26, 6 mg
(10%) of 24, and 5.6 mg (3%) of starting material as colorless
Syn th esis of (()-(2R,3R,1′S,SS)-3-[1′-[(ter t-Bu tyld im -
eth ylsilyl)oxy]-n -bu tyl]-2-(p h en ylsu lfin yl)oxir a n e, (()-
17b, an d (()-(2S,3S,1′S,SS)-3-[1′-[(ter t-Bu tyldim eth ylsilyl)-
oxy]-n -bu tyl]-2-(p h en ylsu lfin yl)oxir a n e, (()-18b. From
NaH (7 mg, 0.30 mmol) in THF (1.90 mL), t-BuOOH (37 µL,
33 mg, 0.37 mmol), and a solution of vinyl sulfoxide (()-6b
(25 mg, 0.074 mmol) in THF (0.50 mL), according to the
general procedure (0 °C, 20 h), a 97:3 mixture of sulfinylox-
iranes (()-17b and (()-18b was obtained. Purification by
chromatography (50-100% CH2Cl2-hexane) gave 19 mg (72%)
of (()-17b and 1 mg (4%) of (()-18b as colorless oils. Data for
(()-17b: Rf ) 0.19 (75% CH2Cl2-hexane); 1H NMR (300 MHz)
δ -0.01 (s, 3 H), -0.02 (s, 3 H), 0.82 (t, 3 H, J ) 7.1 Hz), 0.84
(s, 9 H), 1.23-1.57 (m, 4 H), 3.37 (dd, 1 H, J ) 5.6, 2.0 Hz),
3.45-3.48 (m, 1 H), 3.90 (d, 1 H, J ) 5.6 Hz), 7.51-7.55 (m, 3
H), 7.64-7.67 (m, 2 H); 13C NMR (50 MHz) δ -5.0, -4.6, 14.0,
17.9, 18.3, 25.7 (3 C), 36.7, 59.5, 71.5, 71.6, 124.7 (2 C), 129.4
(2 C), 131.8, 140.2. Partial data for (()-18b: Rf ) 0.24 (75%
oils. Data for 26: Rf ) 0.43 (5% EtOAc- CH2Cl2); [R]20
)
D
1
-46.4 (c ) 0.94); H NMR (200 MHz) δ 1.00 (d, 3 H, J ) 6.3
Hz), 1.09 (s, 9 H), 2.38 (s, 3 H), 3.31 (dd, 1 H, J ) 8.2, 3.8 Hz),
3.93 (d, 1 H, J ) 3.8 Hz), 4.13 (m, 1 H), 7.25-7.46 (m, 10 H),
7.69-7.76 (m, 4 H); 13C NMR (50 MHz) δ 19.3, 20.6, 21.5, 27.0
(3 C), 63.4, 67.8, 74.4, 125.2 (2 C), 127.6 (4 C), 129.7 (2 C),
129.8 (2 C), 130.2 (2 C), 133.3, 135.9 (2 C), 136.0 (2 C), 142.9.
The data for 24 were identical to those found later.
Syn th esis of (+)-(Z)-(2R,3S)-3-[1′-[(ter t-Bu tyld ip h en yl-
silyl)oxy]m eth yl]-2-(p-tolylsu lfon yl)oxir an e, 16. From sulfi-
nyl oxirane 15 (92 mg, 0.204 mmol) in MeOH (2.04 mL) and
MMPP (351 mg, 0.61 mmol), according to the general proce-
1
CH2Cl2-hexane); H NMR (300 MHz) δ -0.08 (s, 3 H), -0.04
4804 J . Org. Chem., Vol. 68, No. 12, 2003

Epoxidation of γ-Hydroxyvinyl Sulfoxide Derivatives
dure (24 h), after chromatography (5-30% EtOAc-hexane),
epoxy sulfone 16 (67.4 mg, 70%) was obtained as a colorless
oil: Rf ) 0.42 (30% EtOAc-hexane); [R]20D ) +77.4 (c ) 0.81);
1H NMR (200 MHz) δ 1.07 (s, 9 H), 2.43 (s, 3 H), 3.51 (dt, 1 H,
J ) 5.7, 3.9 Hz), 3.96 (d, 1 H, J ) 4.0 Hz), 4.25-4.40 (m, 2 H),
7.31-7.41 (m, 8 H), 7.67 (dd, 4 H, J ) 7.8, 2.0 Hz), 7.74 (d, 2
H, J ) 8.4 Hz); 13C NMR (50 MHz) δ 19.2, 21.7, 26.8 (3 C),
60.9, 61.6, 68.2, 127.8 (4 C), 128.5 (2 C), 129.8 (2 C), 130.0 (2
C), 133.0, 133.1, 135.1, 135.6 (4 C), 145.6.
Syn th esis of (()-(2R,3R,1′S)-3-[1′-[(ter t-Bu tyld im eth -
ylsilyl)oxy]-n -bu tyl]-2-(p h en ylsu lfon yl)oxir a n e, (±)-19b.
From sulfinyloxirane (()-17b (28 mg, 0.12 mmol) in MeOH
(1.20 mL) and MMPP (116 mg, 0.23 mmol), according to the
general procedure (2 h), after chromatography (5-40% EtOAc-
hexane), epoxy sulfone (()-19b (28 mg, 95%) was obtained as
a colorless oil: Rf ) 0.59 (75% CH2Cl2-hexane); 1H NMR (300
MHz) δ 0.01 (s, 3 H), 0.05 (s, 3 H), 0.85 (s, 9 H), 0.90 (t, 3 H,
J ) 7.3 Hz), 1.24-1.55 (m, 4 H), 3.52 (ap q, 1 H, J ) 6.0 Hz),
3.63 (dd, 1 H, J ) 5.6, 1.7 Hz), 3.98 (d, 1 H, J ) 1.7 Hz), 7.55-
7.60 (m, 3 H), 7.66-7.69 (m, 1 H), 7.90-7.93 (m, 2 H); 13C NMR
(50 MHz) δ -5.0, -4.6, 14.1, 17.7, 18.3, 25.7 (3 C), 36.9, 60.7,
66.8, 71.0, 128.7 (2 C), 129.4 (2 C), 134.4, 149.1.
Syn th esis of (()-(2R,3R,1′R)-3-[1′-[(ter t-Bu tyld im eth -
ylsilyl)oxy]-n -bu tyl]-2-(p h en ylsu lfon yl)oxir a n e, (()-en t-
20b. From sulfinyloxirane (()-22b (28 mg, 0.12 mmol) in
MeOH (1.20 mL) and MMPP (116 mg, 0.23 mmol), according
to the general procedure (2 h), after chromatography (5-40%
EtOAc-hexane), epoxy sulfone (()-ent-20b (28 mg, 95%) was
obtained as a colorless oil: Rf ) 0.33 (50% CH2Cl2-hexane);
1H NMR (300 MHz) δ -0.05 (s, 3 H), -0.01 (s, 3 H), 0.80 (s, 9
H), 0.90 (t, 3 H, J ) 7.2 Hz), 1.35-1.49 (m, 2 H), 1.50-1.57
(m, 2 H), 3.53 (dd, 1 H, J ) 2.7, 1.6 Hz), 3.89 (td, 1 H, J ) 5.5,
2.7 Hz), 4.08 (d, 1 H, J ) 1.6 Hz), 7.58 (m, 2 H), 7.67 (m, 1 H),
7.91 (m, 2 H); 13C NMR (50 MHz) δ -5.0, -4.7 (2 C), 14.2,
17.7, 25.7 (3 C), 36.9, 59.8, 65.3, 67.7, 126.5, 128.6 (2 C), 129.4
(2 C), 134.3.
MMPP (120.9 mg, 0.19 mmol), according to the general
procedure (3 h), after chromatography (5-30% EtOAc-hex-
ane), 23 (29.7 mg, 95%) was obtained as a colorless oil: Rf )
0.46 (30% EtOAc-hexane); [R]20D ) +55.8 (c ) 0.91); 1H NMR
(300 MHz) δ 1.08 (s, 9 H), 1.19 (d, 3 H, J ) 6.2 Hz), 2.42 (s, 3
H), 3.35 (dd, 1 H, J ) 7.6, 3.7 Hz), 3.91 (d, 1 H, J ) 3.7 Hz),
4.78 (quint, 1 H, J ) 6.2 Hz), 7.29-7.45 (m, 8 H), 7.70-7.76
(m, 6 H); 13C NMR (75 MHz) δ 19.2, 21.7, 26.9 (3 C), 64.9,
65.0, 68.4, 127.5 (2 C), 127.7 (2 C), 128.4 (2 C), 129.6, 129.8,
130.0 (2 C), 133.1, 134.4, 135.7, 135.8 (2 C), 135.9 (2 C), 145.4.
Syn th esis of (-)-(2S,3R,1′S)-3-[1′-[(ter t-Bu tyld ip h en yl-
silyl)oxy]eth yl]-2-(p-tolylsu lfon yl)oxir a n e, 24. From sulfi-
nyloxirane 26 (19.0 mg, 0.041 mmol) in MeOH (0.41 mL) and
MMPP (76 mg, 0.12 mmol), according to the general procedure
(17 h), after chromatography (5-30% EtOAc-hexane), 24 (13.8
mg, 70%) was obtained as a colorless oil: Rf ) 0.25 (15%
EtOAc-hexane); [R]20D ) -47.0 (c ) 0.54); 1H NMR (200 MHz)
δ 1.09 (s, 9 H), 1.28 (d, 3 H, J ) 6.4 Hz), 2.43 (s, 3 H), 3.43
(dd, 1 H, J ) 7.9, 4.0 Hz), 3.91 (d, 1 H, J ) 4.0 Hz), 4.69 (dq,
1 H, J ) 7.7, 6.4 Hz), 7.29-7.43 (m, 10 H), 7.62-7.73 (m, 4
H); 13C NMR (50 MHz) δ 19.3, 21.7, 27.0 (3 C), 66.0, 67.1, 68.7,
127.5 (4 C), 128.5 (2 C), 129.6 (2 C), 129.9 (2 C), 133.8 (2 C),
134.8, 135.9 (2 C), 136.0 (2 C), 145.4.
Ack n ow led gm en t. This research was supported by
DGICYT (Grants PPQ2000-1330 and BQU2001-0582)
and CAM (Grant 08.5/0079.1/2000). We thank J ANS-
SEN-CILAG for additional support. We thank CAM for
a doctoral fellowship to C.M. We are grateful to Profes-
sor S. Valverde and Dr. J . C. Lo´pez (Instituto de
Qu´ımica Orga´nica, CSIC) for encouragement and sup-
port.
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.
Syn th esis of (+)-(2R,3S,1′S)-3-[1′-[(ter t-Bu tyld ip h en yl-
silyl)oxy]eth yl]-2-(p-tolylsu lfon yl)oxir a n e, 23. From sulfi-
nyloxirane 25 (30.3 mg, 0.065 mmol) in MeOH (0.65 mL) and
J O0342828
J . Org. Chem, Vol. 68, No. 12, 2003 4805