Stereoselective nucleophilic epoxidation of vinyl sulfoxides: A novel route to enantiopure sulfinyl oxiranes

Full text of DOI:10.1021/jo9603845

3586
J . Org. Chem. 1996, 61, 3586-3587
Sch em e 1
Ster eoselective Nu cleop h ilic Ep oxid a tion
of Vin yl Su lfoxid es: A Novel Rou te to
En a n tiop u r e Su lfin yl Oxir a n es†,1
Roberto Ferna´ndez de la Pradilla,*,‡ Sonia Castro,‡
Pilar Manzano,‡ J ulia´n Priego,‡ and Alma Viso§
Instituto de Quı´mica Orga´nica, CSIC, J uan de la Cierva, 3,
28006 Madrid, Spain, and Departamento de Qu´ımica
Orga´nica I, Facultad de Quı´mica, Universidad
Complutense, 28040 Madrid, Spain
Received February 27, 1996
Enantiopure sulfinyl oxiranes are versatile synthetic
intermediates2 available by condensation of R-chloroalkyl
p-tolyl sulfoxides with aldehydes or ketones and subse-
quent cyclization. However, this process results in the
formation of two diastereomers due to low 1,3-asym-
metric induction.2b On the other hand, J ackson has
recently shown that (E)-N-[(p-tolylsulfonyl)vinyl]sulfox-
imines undergo nucleophilic epoxidation with LiOO-t-Bu
with complete geometric and facial selectivity to produce
the corresponding oxiranes.3,4 J ackson’s results conclu-
sively established that a chiral sulfoximine sulfur atom
may be a powerful element of stereocontrol in this
process. Within the context of an ongoing project ad-
dressing multiple sulfur to carbon chirality transfer
operations using vinyl sulfoxides, we required an efficient
route to enantiopure vinyl epoxy sulfoxides of general
structure B, R2 ) vinyl (Scheme 1), with high regiocon-
trol, E-Z stereocontrol, and diastereofacial selectivity.
We envisioned that the nucleophilic epoxidation of readily
available5 2-sulfinyl dienes A, R2 ) vinyl, could be a
viable albeit challenging route, and aware of the synthetic
usefulness of sulfinyl oxiranes,2 we undertook the devel-
opment of such a process as a general reaction of alkenyl
sulfoxides. In this paper, we describe our preliminary
results of the unprecedented direct epoxidation of simple
vinyl sulfoxides.
At the inception of this research we recognized two
difficulties associated with our approach to epoxy sul-
foxides B (Scheme 1), namely, alkenyl sulfoxides, A, are
only moderately electron deficient6 and they are readily
oxidized to the corresponding sulfones C which may
undergo nucleophilic epoxidation to yield racemic D. In
contrast, vinyl sulfoximines are powerful Michael accep-
tors and cannot be oxidized readily. In addition, the
desired sulfinyl oxiranes B should undergo oxidation even
more readily to produce epoxy sulfones D. Since most
Weitz-Scheffer reaction conditions are also relatively
strongly oxidizing, the viability and, at best, the facial
selectivity of this epoxidation became a matter of concern.
Considering this, we selected simple vinyl sulfoxides 1-6
and dienyl sulfoxides 7 and 85,7 as substrates for this
study, and the results obtained are shown in Table 1.
At the initial stage of this research we focused our
efforts on keto vinyl sulfoxide 1 to establish whether a
sufficiently activated substrate could undergo epoxidation
without significant oxidation to the sulfone. Indeed,
treatment of 1 with LiOO-t-Bu led to a mixture of four
diastereomeric epoxy sulfoxides, presumably geometric
and facial isomers, with low selectivity. This disappoint-
ing result demonstrated that, at least for short reaction
times, these conditions were compatible with the sulfinyl
functionality.
The reactivity of simple E alkenyl sulfoxides 2 and 3
was then studied. Phenyl-substituted sulfoxide 2 was
found to be totally unreactive under a number of experi-
mental conditions.8 The well-known lack of reactivity of
2 with nucleophiles9 prompted us to study 3, but unfor-
tunately, our initial efforts led to almost exclusive forma-
tion of sulfone 9. After considerable experimentation,10
we succeeded in obtaining the desired epoxy sulfoxides
10 and 11 (Table 1, entry 3) albeit in low selectivity and
accompanied by relatively large amounts of sulfone 9.
The influence of the alkene geometry on the process
was then addressed (Table 1, entries 4 and 5), and both
Z substrates studied, 4 and 5, afforded good yields of
epoxy sulfoxides 13 and 16 with remarkable stereoselec-
tivities. Furthermore, overoxidation to sulfones 12 and
15 was hardly a problem in these cases.11 In view of the
high reactivity displayed by 5, we studied tert-butyl
sulfoxide 6 and, while the reaction was somewhat slower
than for the p-tolyl analogue 5, practically a single isomer
of an epoxy sulfoxide was obtained in excellent yield.12
* To whom correspondence should be addressed. Tel.: 34-(1)-562-
2900 ext 210. Fax: 34-(1)-564-4853. E-mail: RIF@CC.CSIC.ES.
† Dedicated to the memory of Professor Fe´lix Serratosa.
‡ Instituto de Qu´ımica Orga´nica.
(6) Simple vinyl sulfoxides display a relatively low reactivity with
nucleophiles. See, for instance: The Chemistry of Sulphones and
Sulphoxides; Patai, S., Rappoport, Z., Stirling, C. J . H., Eds.; J ohn
Wiley & Sons: New York, 1988.
§ Universidad Complutense.
(7) Substrates 2-5 were prepared in one step from commercially
available reagents by the method of Craig. See: Craig, D.; Daniels,
K.; McKenzie, A. R. Tetrahedron 1993, 49, 11263-11304. Alternatively,
3 could be prepared with high selectivity in two steps according to:
Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J . Org.
Chem. 1987, 52, 1078-1082. For the preparation of 1 see: Marino, J .
P.; Viso, A.; Ferna´ndez de la Pradilla, R.; Ferna´ndez, P. J . Org. Chem.
1991, 56, 1349-1351. Racemic 6, available in our laboratories from a
previous project, was prepared from 1-hexyne by free radical addition
of 2-methyl-2-propanethiol and oxidation. All new products reported
here have been fully characterized by spectroscopic techniques.
(8) Forcing reaction conditions (long reaction times, higher temper-
atures) led to oxidation to the vinyl sulfone and, in some cases,
subsequent epoxidation. For the oxidation of sulfoxides with t-BuOOH,
see: Breton, G. W.; Fields, J . D.; Kropp, P. J . Tetrahedron Lett. 1995,
36, 3825-3828.
(1) Taken in part from the M.S. Theses of S.C., P.M., and J .P.,
Instituto de Qu´ımica Orga´nica, CSIC.
(2) (a) For a review, see: Satoh, T.; Yamakawa, K. Synlett 1992,
455-468. (b) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J . Org.
Chem. 1989, 54, 3130-3136. (c) For an isolated example of an
alternative method, see: Tsuchihashi, G.; Mitamura, S.; Ogura, K.
Tetrahedron Lett. 1974, 455-458.
(3) 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.
(4) For leading references on related nucleophilic epoxidations,
see: (a) J ackson, R. F. W.; Standen, S. P.; Clegg, W. J . Chem. Soc.,
Perkin Trans. 1 1995, 149-156. (b) Linderman, R. J .; Claasen, R. J .,
II; Viviani, F. Tetrahedron Lett. 1995, 36, 6611-6614. (c) Ambroise,
L.; J ackson, R. F. W. Tetrahedron Lett. 1996, 37, 2311-2314.
(5) See: Paley, R. S.; Weers, H. L.; Ferna´ndez de la Pradilla, R.;
Castro, S. Tetrahedron Lett. 1995, 36, 3605-3608 and references cited
therein.
(9) Pyne, S. G.; Bloem, P.; Chapman, S. L.; Dixon, C. E.; Griffith,
R. J . Org. Chem. 1990, 55, 1086-1093.
S0022-3263(96)00384-2 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 11, 1996 3587
Ta ble 1. Dia ster eoselective Ep oxid a tion of Vin yl Su lfoxid es
entry
substrate
M
time (min)
20
sulfonea
R-epoxidea,b
â-epoxidea,b
yieldc (%)
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
3
4
8
Li
Li
Li
Li
Li
Li
Li
Li
Na
Na
Li
see text
NR
70
84
74
79
75
83
75
77
92
240
240
20
210
120
120
90
9 (25)
12 (6)
10 (17)
13 (86)
16 (98)
19 (98)
22 (20)
25 (77)
10 (4)
11 (58)
14 (8)
17 (2)
15 (-)
18 (-)
21 (trace)
24 (-)
9 (13)
20 (2)
23 (80)
26 (23)
11 (83)
14 (1)
9d
10d
11e
60
120
12 (3)
13 (96)
25 (-)
24 (100)f
26 (-)
a
b
Ratios of products measured by integration of the 300 MHz 1H NMR spectra of crude reaction mixtures are in parentheses. Tentative
assignments except for 22, 23, 25, and 26. See ref 15. c Unoptimized combined yields of pure products. Generated from NaH and HOO-
d
t-Bu. e Reaction conducted in Et2O. f Sulfone 24 had 84% ee.
Finally, we focused on the epoxidation of 2-sulfinyl dienes
7 and 8 (Table 1, entries 7 and 8), which displayed
moderate stereoselectivities under standard reaction
conditions to produce good yields of vinyl epoxy sulfoxides
22, 23, 25, and 26.
The effect of the metal cation and solvent on this
epoxidation was then briefly examined. The use of
NaOO-t-Bu (Table 1, entries 9 and 10) resulted in a
substantial enhancement of the stereoselectivity along
with less overoxidation to the sulfones (compare with
entries 3 and 4 of Table 1).13 On the other hand, the
epoxidation of diene 8 with LiOO-t-Bu in Et2O (Table 1,
entry 11) led to an excellent yield of vinyl epoxy sulfone
24 (83% ee).14
While the general structure and geometry of these
epoxy sulfoxides could be readily established from their
1H and 13C NMR spectral features, determination of their
relative configuration required a chemical correlation
which was carried out for vinyl epoxides 23 and 25.15 The
stereochemistry of the other epoxides gathered in Table
1 was tentatively assigned by analogy with that of 23
and 25.
The observed stereochemical outcome of this process
may be rationalized in terms of the different reactive
conformations proposed by Pyne.9 Thus, a syn coplanar
SdO/CdC conformation would lead to preferred â-attack
for E substrates. Alternatively, Z sulfoxides would
undergo selective R-attack due to a conformational
change to an s-trans coplanar SdO/CdC conformation.
While these selectivities may be accounted for by steric
considerations, some directing effect of the sulfinyl
oxygen by coordination with the metal cannot be ruled
out at this point.
In summary, these results conclusively demonstrate
that readily available vinyl sulfoxides may undergo clean
nucleophilic epoxidation with moderate to excellent di-
astereofacial selectivity and complete preservation of the
geometry of the starting material and in synthetically
useful yields. This methodology should allow for expedi-
ent access to a variety of enantiopure epoxy sulfoxides
and epoxy sulfones, versatile synthetic intermediates.2,3,16
We are currently exploring the scope, limitations, and
possible improvements of this protocol as well as applica-
tions of our vinyl epoxy sulfoxides in synthesis.
Ack n ow led gm en t. This research was supported by
DGICYT (Grant Nos. PB93-0154 and PB94-0104). We
thank Professors B. Rodr´ıguez and S. Valverde for
encouragement and support.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for all new compounds (10
pages).
J O9603845
(14) The optical purity was determined by comparison of the optical
rotation of 24 (entry 11, [R] ) +82.8) with that of an enantiomerically
pure sample ([R] ) +99.5) obtained from sulfinyl epoxide 25 (Oxone,
MeOH). This observation suggests that in Et2O the epoxidation occurs
with better selectivity (ca. 90:10) than in THF (77:23) and that
sulfoxides 25 and 26 are oxidized very readily to 24. Efforts to control
this undesired oxidation in Et2O are underway.
(15) This correlation entailed hydrogenation of unsaturated epoxides
23 and 25 and comparison of the data of the resulting sulfinyl oxiranes
with that of enantiomeric or diastereomeric epoxides prepared from
(Rs)-1-chloro-n-propyl p-tolyl sulfoxide and n-pentanal by the method
of Yamakawa (ref 2) of known stereochemical course. These experi-
ments will be described in detail in a full account of this research.
(16) (a) For the R-lithiation of sulfonyl oxiranes, see: Ashwell, M.;
Clegg, W.; J ackson, R. F. W. J . Chem. Soc., Perkin Trans. 1 1991, 897-
908. (b) For the generation of oxiranyllithium reagents from sulfinyl
oxiranes by ligand exchange, see: Satoh, T.; Horiguchi, K. Tetrahedron
Lett. 1995, 36, 8235-8238.
(10) The qualitative influence of stoichiometry, temperature, con-
centration, and reaction time on this process was screened. In many
cases, very careful monitoring of the reaction by TLC was crucial since
vinyl and epoxy sulfoxides present very similar chromatographic
mobilities.
(11) An authentic sample of enantiomerically pure sulfone 15 was
prepared by oxidation (MMPP, MeOH, rt) of epoxy sulfoxide 16.
(12) The use of tert-butyl sulfoxides allows for improved stereocontrol
vs their p-tolyl analogues in some cases. For the preparation of optically
pure tert-butyl sulfoxides, see: Khiar, N.; Ferna´ndez, I.; Alcudia, F.
Tetrahedron Lett. 1994, 35, 5719-5722 and references cited therein.
(13) To the best of our knowledge, NaOO-t-Bu has not been used
previously for related processes.