Preparation of enantiomerically enriched (2R,3R)- or (2S,3S)-trans-2,3-diaryloxiranes via camphor-derived sulfonium ylides

Article abstract of DOI:10.1021/jo951442+

Easily available D-(+)-camphor-derived sulfides 3, 4, 6, and 7 were employed for enantioselective epoxidation via an ylide route. When benzylated or methylated sulfides were used as reagents or mediators for benzylidene transfer, stoichiometric and catalytic epoxidations were realized, respectively. Opposite asymmetric induction was achieved only when sulfides containing exo- (3 and 4) and endo- (6 and 7) alkylthio groups were used. That is, both (+)- and (-)-trans-diaryloxiranes could be obtained in excellent yields and moderate to good ee values under extremely mild conditions from the same chiral pool-derived reagents. A nonbonded interaction between the free OH in the ylides from sulfides (3, 6, and 7) and the carbonyl group of aldehydes controls the approach of the substrates to the ylidic carbon preferentially at one specified face and therefore leads to a more efficient asymmetric induction than that in the case of the ylide from methyl-protected hydroxylated sulfides 4, which cannot cause such an interaction. The same opposite asymmetric induction was also observed in the catalytic reaction with methyl-protected hydroxylated sulfide 4b and unprotected hydroxylated sulfide 3b.

Full text of DOI:10.1021/jo951442+

J . Org. Chem. 1996, 61, 489-493
489
P r ep a r a tion of En a n tiom er ica lly En r ich ed (2R,3R)- or
(2S,3S)-tr a n s-2,3-Dia r yloxir a n es via Ca m p h or -Der ived Su lfon iu m
Ylid es
An-Hu Li, Li-Xin Dai,* Xue-Long Hou, Yao-Zeng Huang,* and Feng-Wei Li
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received August 3, 1995X
Easily available D-(+)-camphor-derived sulfides 3, 4, 6, and 7 were employed for enantioselective
epoxidation via an ylide route. When benzylated or methylated sulfides were used as reagents or
mediators for benzylidene transfer, stoichiometric and catalytic epoxidations were realized,
respectively. Opposite asymmetric induction was achieved only when sulfides containing exo- (3
and 4) and endo- (6 and 7) alkylthio groups were used. That is, both (+)- and (-)-trans-
diaryloxiranes could be obtained in excellent yields and moderate to good ee values under extremely
mild conditions from the same chiral pool-derived reagents. A nonbonded interaction between the
free OH in the ylides from sulfides (3, 6, and 7) and the carbonyl group of aldehydes controls the
approach of the substrates to the ylidic carbon preferentially at one specified face and therefore
leads to a more efficient asymmetric induction than that in the case of the ylide from methyl-
protected hydroxylated sulfides 4, which cannot cause such an interaction. The same opposite
asymmetric induction was also observed in the catalytic reaction with methyl-protected hydroxylated
sulfide 4b and unprotected hydroxylated sulfide 3b.
In tr od u ction
After the emergence of an ingenious idea for the first,
although failed, attempt6a to transfer the methylene
group from an optically active sulfonium ylide with a
chiral center at the sulfur atom to a CdO bond, several
sulfides6b-h have been used for producing enantiomeri-
cally enriched epoxides. Among them, Durst’s sulfides
derived from (+)-camphoric acid give the highest levels
of enantioselectivity.6d However, the long synthetic route
led to low overall yields, poor stereoselectivity, a mixture
of trans- and cis- epoxides, and a side reaction, namely
â-elimination, which made this method somewhat im-
practical. Additionally, all other examples either require
strict reaction conditions and operations or give only low
yields and/or ee values. Our search for convenient
methods to prepare functionalized optically active ep-
oxides,7 combined with our experiences in ylide chemis-
try,8 led us to explore enantioselective epoxidation by way
The notable biological significance1 and various chemi-
cal transformations2 make nonracemic epoxides one of
the most useful synthetic intermediates.3 The develop-
ment of methods for the preparation of this type of
compound is always a subject of great challenge. The
recorded ways for this aim are chiefly as follows: (a)
enantiofacially differential oxidation of a prochiral CdC
bond;4 (b) enantioselective alkylidenation of a CdO bond,
such as via an ylide route or a Darzens reaction.
Although the former method has afforded much success,
the structural requirements of the substrates are a
limiting prerequisite. The latter strategy provides an
alternative approach in solving this problem. Enanti-
oselective epoxidation via an ylide route is an approach
easy to perform but relatively undeveloped to date.5,6
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) (a) Hatakeyama, S.; Ochi, N.; Takano, S. Chem. Pharm. Bull.
1993, 41, 1358-1361. (b) J erina, D. M.; Daly, J . W. Science 1974, 185,
573-582. (c) Rokach, J .; Young, R. N.; Kakushima, M.; Lau, C.-K.;
Seguin, R.; Frenette, R.; Guindon, Y. Tetrahedron Lett. 1981, 22, 979-
982. (d) Becker, A. R.; J anusz, J . M.; Bruice, T. C. J . Am. Chem. Soc.
1979, 101, 5679-5687. (e) Sato, F.; Kobayashi, Y. Synlett 1992, 849-
857.
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L. In The Chemistry of Functional Groups, Supplement E; Patai, S.,
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(3) (a) Hudlicky, T.; Tian, X.; Ko¨nigsberger, K.; Rouden, J . J . Org.
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Chem. 1995, 60, 790-791. (d) Kim, N.-S.; Choi, J .-R.; Cha, J . K. J .
Org. Chem. 1993, 58, 7096-7099. (f) Soulie´, J .; Boyer, T.; Lallemand,
J . Y. Tetrahedron, Asymmetry 1995, 6, 625-636.
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Sharpless, K. B. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 7, pp 389-436.
For Mn salen complex-catalyzed asymmetric epoxidation: (b) Zhang,
W.; Loebach, J . L.; Wilson, S. R.; J acobsen, E. N. J . Am. Chem. Soc.
1990, 112, 2801-2803. For a review on metalloporphyrin-catalyzed
asymmetric epoxidation: (c) Collman, J . P.; Zhang, X.; Lee, V. J .;
Uffelman, E. S.; Brauman, J . I. Science 1993, 261, 1404-1411. Other
methods for asymmetric epoxidation: (d) Koch, A.; Reymond, J .-L.;
Lerner, R. A. J . Am. Chem. Soc. 1994, 116, 803-804. (e) Allain, E. J .;
Hager, L. P.; Deng, L.; J acobsen, E. N. J . Am. Chem. Soc. 1993, 115,
4415-4416. (f) Davis, F. A.; Harakal, M. E.; Awad, S. B. J . Am. Chem.
Soc.1983, 105, 3123-3126.
(5) Asymmetric epoxidation with sulfoximine ylides: (a) J ohnson,
C. R.; Schroeck, C. W. J . Am. Chem. Soc. 1968, 90, 6852-6854. (b)
J ohnson, C. R.; Schroeck, C. W. J . Am. Chem. Soc. 1973, 95, 7418-
7423. (c) J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J . Am. Chem.
Soc. 1973, 95, 7424-7431. (d) Taj, S. S.; Soman, R. Tetrahedron,
Asymmetry 1994, 5, 1513-1518. With arsonium ylides: (e) Allen, D.
G.; Roberts, N. K.; Wild, S. B. J . Chem. Soc., Chem. Commun. 1978,
346-347. (f) Allen, D. G.; Wild, S. B. Organometallics 1983, 2, 394-
399. With dimethylsulfonium methylide in the presence of chiral phase-
transfer catalysts: (g) Hiyama, T.; Mishima, T.; Sawada, H.; Nozaki,
H. J . Am. Chem. Soc. 1975, 97, 1626-1627. With chiral sulfimides:
(h) Baird, C. P.; Taylor, P. C. J . Chem. Soc., Chem. Commun. 1995,
893-894.
(6) Asymmetric epoxidation with chiral sulfonium ylides: (a) Trost,
B. M.; Hammen, R. F.; J . Am. Chem. Soc.1973, 95, 962-964. (b)
Furukawa, N.; Sugihara, Y.; Fujihara, H. J . Org. Chem. 1989, 54,
4222-4224. (c) Breau, L.; Ogilvie, W. W.; Durst, T. Tetrahedron Lett.
1990, 31, 35-38. (d) Breau, L.; Durst, T. Tetrahedron, Asymmetry 1991,
2, 367-370. (e) Solladie´-Cavallo, A.; Adib, A. Tetrahedron 1992, 48,
2453-2464. (f) Aggarwal, V. K.; Kalomiri, M.; Thomas, A. P. Tetra-
hedron, Asymmetry 1994, 5, 723-730. (g) Aggarwal, V. K.; Abdel-
Rahman, H.; J ones, R. V. H.; Lee, H. Y.; Reid, B. D. J . Am. Chem.
Soc. 1994, 116, 5973-5974. (h) Solladie´-Cavallo, A.; Diep-Vohuule, A.
J . Org. Chem. 1995, 60, 3494-3498.
(7) (a) Dai, L.-X.; Lou, B.-L.; Zhang, Y.-Z.; Guo, G.-Z. Tetrahedron
Lett. 1986, 27, 4343-4346. (b) Dai, L.-X.; Lou, B.-L.; Zhang, Y.-Z. J .
Am. Chem. Soc. 1988, 110, 5195-5196. (c) Lai, J .-Y.; Wang, F.-S.; Guo,
G.-Z.; Dai, L.-X. J . Org. Chem. 1993, 58, 6944-6946. (d) Lai, J .-Y.;
Shi, X.-X.; Dai, L.-X. J . Org. Chem. 1992, 57, 3485-3487.
0022-3263/96/1961-0489$12.00/0 © 1996 American Chemical Society

490 J . Org. Chem., Vol. 61, No. 2, 1996
Li et al.
Sch em e 1
Sch em e 3
uration of C2 connected to the OH group in 6 and 712 was
1
in accordance with the H-1H NOESY maps of 6a and
6b. In the NOESY map of 6b (Scheme 3), the 3.82 ppm
doublet of doublet correlates to the 3.39 ppm multiplet.
This suggests that the two protons (connected with C2
and C3) have a cis orientation on the ring, i.e., the OH
group is directed to the endo position. The same cor-
relation exists in compound 6a . The OH groups in 7a
and 7b are therefore assumed to be in the exo-position.
The configurational assignment of all other compounds
was in accordance with the literature results.10
Sch em e 2
Stoich iom etr ic En a n tioselective Ep oxid a tion via
Ylid e of Su lfid es 3a , 4a , 6a , a n d 7a . All reported
examples5,6 of enantioselective epoxidation via an ylide
route, except those of Furukawa6b and Aggarwal,6g are
stoichiometric reactions, in which sulfonium salts, if
sulfonium ylides are involved, must first be prepared.
Sometimes silver salts (AgBF4 or AgClO4) are required
in preparation of these sulfonium salts.
We found that sulfides 3a , 4a , 6a , and 7a reacted
smoothly with methyl iodide to furnish the corresponding
sulfonium salts without the aid of silver salts. This
suggested that this ylide reaction could be carried out in
one pot. On the basis of our successful experiences with
solid-liquid phase-transfer technology in arsonium and
telluronium ylide chemistry,8b,13 we tried the reaction of
3a , 4a , 6a , and 7a with various aldehydes in the presence
of MeI and solid KOH in acetonitrile at room temperature
(Table 1).
For aromatic aldehydes, the reaction proceeded per-
fectly to give completely the trans products, with excellent
yields in most cases, and moderate to good ee values (19-
77%). Any efforts to extend this reaction to aliphatic and
heteroaromatic aldehydes and ketones were unsuccessful
because of side reactions of aliphatic and heteroaromatic
aldehydes, and the low reactivity of ketones.
It is interesting that the opposite asymmetric induction
was achieved only when 3a (benzylthio group at exo
position) and 6a or 7a (benzylthio group at endo position)
were applied as chiral auxiliaries. This represents an
efficient preparation of enantiomerically enriched (+)-
and (-)-trans-diaryloxiranes from ylides with both high
yields and reasonable ee values, although both (+)- and
(-)-enantiomers have also been obtained in low yields
in some cases.6b,d The effect of asymmetric induction from
3a (exo-benzylthio) was generally better than that from
6a or 7a (endo-benzylthio).
It is noteworthy that the free OH group at C2 plays an
important role; when the OH was converted to a meth-
oxyl group, both the yield and the ee value of the
resulting epoxide were greatly lowered. (entry 2 vs entry
4 in Table 1). This led us to postulate that there may be
a nonbonded interaction between the OH and the car-
of ylides. We disclose herein our methods for preparing
(2R,3R)-(+)- and (2S,3S)-(-)-diaryloxiranes through chiral
sulfonium ylides with excellent yields and moderate to
good ee values.
Resu lts a n d Discu ssion
Syn th esis of Ylid e P r ecu r sor s 3a , 3b, 4a , 4b, 6a ,
6b, 7a , a n d 7b. Since the appearance of chiral sulfides
2, 3, and 5 derived from D-(+)-camphor (1), an easily
available chiral pool,9 in 1988,10 they have found several
applications in asymmetric synthesis and reactions.11 In
some cases, satisfactory results could be achieved. In
order to examine the effect of these sulfides upon asym-
metric induction through ylide epoxidation, we prepared
sulfides 3, 4, 6, and 7 by methods similar to that used
by Haynes10 for the preparation of 2, 3, and 5 with
reasonable yields and optical purity (Scheme 1 and
Scheme 2). Sulfides 4, 6, and 7 were unreported and
were fully characterized. The assignment of the config-
(8) (a) Huang, Y.-Z.; Shen, Y.-C. Adv. Organomet. Chem. 1982, 20,
115-157. (b) Shi, L.; Wang, W.; Wang, Y.; Huang, Y.-Z. J . Org. Chem.
1989, 54, 2027-2028. (c) Zhou, Z.-L; Huang, Y.-Z.; Shi, L.-L. J . Chem.
Soc., Chem. Commun. 1992, 986-988. (d) Wang, W.-B.; Huang, Y.-Z.
In Advances in Organic Synthesis, Dai, L.-X.; Qian, Y.-L., Eds.;
Chemical Industry Press: Beijing, 1993; pp 301-347 (in Chinese).
(9) For
a recent review on camphor-derived chiral auxiliaries:
Oppolzer, W. Tetrahedron 1987, 43, 1969-2004.
(10) Goodridge, R. J .; Hambley, T. W.; Haynes, R. K.; Ridley, D. D.
J . Org. Chem. 1988, 53, 2881-2889.
(11) (a) Corey, E. J .; Chen, Z.; Tanoury, G. J . J . Am. Chem. Soc.
1993, 115, 11000-11001. (b) Hung, S.-M.; Lee, D.-S.; Yang, T.-K.
Tetrahedron, Asymmetry 1990, 1, 873-876. (c) Yang, T.-K.; Hung, S.-
M.; Chen, C.-Z.; J iang, Y.-Z.; Mi, A.-Q. Youji Huaxue 1993, 13, 183-
185. (d) Yang, T.-K.; Chen, R.-Y.; Lee, D.-S.; Peng, W.-S.; J iang, Y.-Z.;
Mi, A.-Q.; J ong. T.-T. J . Org. Chem. 1994, 59, 914-921. (e) Lee, D.-S.;
Hung, S.-M.; Lai, M.-C.; Chu, H.-Y.; Yang, T.-K. Org. Prep. Proc. Int.
1993, 25, 673-679.
(12) The assignment of the configuration at C3 in 6 and 7 was given
in the light of known results.10
(13) (a) Huang, Y.; Shi, L.; Yang, J . Tetrahedron Lett. 1985, 26,
6447-6448. (b) Zhou, Z.-L.; Sun, Y.-S.; Shi, L.-L.; Huang, Y.-Z. J . Chem.
Soc., Chem. Commun. 1990, 1439-1440.

Preparation of trans-2,3-Diaryloxiranes
J . Org. Chem., Vol. 61, No. 2, 1996 491
Ta ble 1. P r ep a r a tion of tr a n s-2,3-Dia r yloxir a n es 10 by Stoich iom etr ic En a n tioselective Ep oxid a tion via Ylid es of
Su lfid e 3a , 4a , 6a , a n d 7a a
entry
sulfide
R′
yield of 10,b %
[R]20 of 10 (in EtOH)
ee of 10,c %
configuration of 10d
D
1
2
3
4
5
6
7
8
9
3a
3a
3a
4a
6a
6a
6a
7a
7a
7a
Ph
87
96
89
48
94
92
90
98
89
90
+253° (c, 0.98)
+279° (c, 1.02)
+273° (c, 1.22)
+69° (c, 1.43)
-127° (c, 1.23)
-118° (c, 1.37)
-113° (c, 1.45)
-115° (c, 1.30)
-125° (c, 1.09)
-117° (c, 0.88)
74
77
72
19
35
35
32
32
37
33
(2R,3R)
(2R,3R)
(2R,3R)
(2R,3R)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
p-ClC6H4
p-MeC6H4
p-ClC6H4
p-ClC6H4
Ph
p-MeC6H4
p-ClC6H4
Ph
10
p-MeC6H4
a
All reactions were carried out under solid-liquid phase transfer conditions at room temperature in acetonitrile (reagent grade, need
not be dried before use). Isolated yields based on sulfides. trans-10 was the only product, no cis-isomer was detected. c Calculated on the
b
basis of the following specific rotations reported for optically pure compounds:15 (2R,3R)-2-(p-chlorophenyl)-3-phenyloxirane (10b), [R]D
+362° (c 1.36, EtOH); (2R,3R)-2-phenyl-3-phenyloxirane (10a ), [R]D +342° (c 1.11, EtOH); (2R,3R)-2-(p-tolyl)-3-phenyloxirane (10c), [R]D
d
+351° (c 1.14, EtOH). The absolute configuration of all products was assigned through comparison of the sign of specific rotations with
the literature data.
Sch em e 4
bromide and aldehydes. The catalytic epoxidation pro-
ceeded smoothly in the presence of 0.2 equiv of the above-
mentioned chiral sulfides. Some results are summarized
in Table 2.
In these reactions, the sulfides were converted initially
to sulfonium salts 11 by benzyl bromide and then to the
corresponding ylide 9 in situ under phase-transfer condi-
tions. Ylide 9 was subsequently reacted with aldehydes
to furnish epoxides and release 3b and permit it to enter
a new cycle (Scheme 5).
As expected, the opposite asymmetric induction was
again observed in the catalytic reaction when 3b, which
contains an exo-methylthio group, and 6b or 7b, which
contains an endo-methylthio group, were used (entries
1-3 vs entries 7-12 in Table 2).
These results are quite reasonable because the cata-
lytic reaction shared the same reactive intermediate
sulfonium ylide 9 with the stoichiometric reaction. Sur-
prisingly, the opposite asymmetric induction in the
catalytic epoxidation was also observed in the cases using
3b, which possesses a free OH group, and 4b, which
contains a methyl-protected OH group, although the
asymmetric induction of the latter was rather low (entries
1-3 vs entries 4-6 in Table 2). This phenomenon had
been reported by Furukawa et al.6b
To optimize the reaction conditions, the effects of
solvents and bases were investigated. In strong polar
solvents like DMSO and DMF, the ee values of products
were decreased. Under other conditions, the ee values
remained nearly the same. In commonly used THF, the
yields were reasonably low due to the low solubility of
KOH leading to difficulties in producing ylides. Aceto-
nitrile was the best solvent for this reaction, and strong
bases like KOH(s), NaOH(s), and aqueous NaOH are
useful. Solid KOH seems to be the most suitable base
when convenience of operation is taken into account.
The investigation of the effect of the amount of sulfides
on this catalytic reaction showed that an increase in the
amount of sulfides did not influence the ee values, but
did shorten the reaction time and improve the yields
(Table 3). From a practical standpoint, 20 mol % of
sulfides is suitable for the catalytic reaction. To our
knowledge, only two catalytic examples of ylide asym-
bonyl group of aldehydes before attack by an ylide
(Scheme 4). This interaction causes the aldehydes to
approach the reactive site of the ylide preferentially from
the si-face, and the aldehyde carbonyl to be attacked on
the re-face. The stereochemical outcome of our reaction
could be rationalized with this assumption (Scheme 4).
Ca ta lytic En a n tioselective Ep oxid a tion via Ylid e
of Su lfid es 3b, 4b, 6b, a n d 7b. Since chiral substances
other than natural products are generally difficult to
obtain, an attempt to make a stoichiometric reaction
catalytic is believed to be of practical significance.8b,14
Clearly, sulfonium salt 8 (Scheme 4) could be prepared
either by the methylation of 3a or by the benzylation of
3b. In addition, the stoichiometric ylide epoxidation was
realized through the transfer of a benzylidene group of
ylide 9 instead of a methylene group. Therefore, it is
possible to make this reaction catalytic when 3b, 4b, 6b,
or 7b are used to mediate the reaction between benzyl
(14) (a) Huang, Y.-Z.; Shi, L.-L.; Li; S.-W.; Wen, X.-Q. J . Chem. Soc.,
Perkin Trans. 1 1989, 2397-2399. (b) Zhou, Z.-L.; Shi, L.-L.; Huang,
Y.-Z. Tetrahedron Lett. 1990, 31, 7657-7660.

492 J . Org. Chem., Vol. 61, No. 2, 1996
Li et al.
Ta ble 2. P r ep a r a tion of tr a n s-2,3-Dia r yloxir a n es 10 by Ca ta lytic En a n tioselective Ep oxid a tion via Ylid es of Su lfid e 3b,
4b, 6b, a n d 7ba
entry
sulfide
R′
yield of 10,b %
[R]20D of 10 (in EtOH)
ee of 10,c %
configuration of 10d
1
2
3
4
5
6
7
8
9
3b
3b
3b
4b
4b
4b
6b
6b
6b
7b
7b
7a
Ph
97 (58e, 50f)
+144° (c, 1.23)
+217° (c, 1.32)
+125° (c, 1.03)
-17° (c, 1.01)
-14° (c, 0.44)
-5° (c, 1.08)
42 (11e,47f)
(2R,3R)
(2R,3R)
(2R,3R)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
(2S,3S)
p-ClC6H4
p-MeC6H4
p-ClC6H4
Ph
p-MeC6H4
p-MeC6H4
p-ClC6H4
Ph
93 (62e, 50f)
60 (11e, 43f)
89 (39f)
97
90
94
94
96
96
94
92
36 (43f)
4.7
4.1
1.4
34
40
29
15
20
-119° (c, 1.74)
-146° (c, 1.35)
-98° (c, 1.15)
-53° (c, 0.96)
-67° (c, 1.0)
10
11
12
p-ClC6H4
Ph
p-MeC6H4
90
-66° (c, 2.1)
19
a
All reactions were carried out under solid-liquid phase transfer conditions at room temperature in acetonitrile (reagent grade, need
not be dried before use). Isolated yields based on aldehydes. trans-10 was the only product, no cis-isomer was detected. c Calculated on
b
the basis of the following specific rotations reported for optically pure compounds:15 (2R,3R)-2-(p-chlorophenyl)-3-phenyloxirane (10b),
[R]D +362° (c 1.36, EtOH); (2R,3R)-2-phenyl-3-phenyloxirane (10a ), [R]D +342° (c 1.11, EtOH); (2R,3R)-2-(p-tolyl)-3-phenyloxirane (10c),
d
[R]D +351° (c 1.14, EtOH). The absolute configuration of all products was assigned through comparison of the sign of specific rotations
with the literature data. e Taken from reference 6g. A mixture of trans and cis epoxides (for benzaldehyde, trans/cis: 86/14; for
p-chlorobenzaldehyde, trans/cis: 82/18). In both cases, the ee values belong to the trans isomer. f Taken from reference 6b.
Sch em e 5. Ca ta lytic Cycle for F or m a tion of
Oxir a n es
be carried out under strict conditions, and only 11% ee
was observed. Their results may also be found in Table
2. The epoxides obtained by Aggarwal’s method are a
mixture of trans and cis isomers, while our epoxides are
obtained solely as trans compounds.
Con clu sion s
To examine the effect of asymmetric induction of
camphor-derived reagents in ylide epoxidation, chiral
sulfides 3-7 were synthesized from D-(+)-camphor. When
benzylated sulfides 3a , 4a , 6a , or 7a were employed in
the ylide reaction, a stoichiometric enantioselective ep-
oxidation was realized. An efficient catalytic ylide ep-
oxidation was achieved when 3b, 4b, 6b, or 7a were used
as mediators. The opposite asymmetric induction, which
led to the synthesis of both (+)- and (-)-trans-diarylox-
iranes 10, was achieved only when exo-alkylthio-substi-
tuted sulfide 3a , 3b, or 4a and endo-alkylthio-substituted
sulfide 6a , 6b, 7a , or 7b were used, respectively. An
investigation of the function of a free OH group in 3a
and 3b showed that both yields and ee values were
decreased when the OH was methylated in the case of
3a vs 4a , and the signs of optical rotations were even
reversed in the case of 3b vs 4b. This constitutes a clear
metric epoxidation have appeared in the literature.6b,g
Furukawa’s6b method suffered from relatively low yields
and ee values; Aggarwal’s catalytic epoxidation6g had to
Ta ble 3. Effects of th e Am ou n t of Su lfid e 3b on th e Yield s a n d ee Va lu es of tr a n s-10b in Ca ta lytic En a n tioselective
Ep oxid a tion
entry
amount of 3b, %
reaction time (h)
yield of 10b,a
%
[R]20 of 10b (in EtOH)
ee of 10b,b %
configuration of 10bc
D
1
2
3
4
5
5
10
20
50
100
24
24
15
12
12
24
61
93
95
97
+186° (c, 1.23)
+208° (c, 1.67)
+217° (c, 1.32)
+193° (c, 1.08)
+201° (c, 1.78)
52
58
60
53
56
(2R,3R)
(2R,3R)
(2R,3R)
(2R,3R)
(2R,3R)
a
b
Isolated yields based on aldehyde; trans-10b was the only product, no cis-isomer was detected. Calculated on the basis of the following
specific rotations reported for optically pure compound:15 (2R,3R)-2-(p-chlorophenyl)-3-phenyloxirane (10b), [R]D +362° (c 1.36, EtOH).
c The absolute configuration of the product was assigned through comparison of the sign of specific rotation with the literature data.

Preparation of trans-2,3-Diaryloxiranes
J . Org. Chem., Vol. 61, No. 2, 1996 493
anhydrous MgSO4, and purified by chromatography on silica
gel column with ethyl acetate/petroleum ether (60-90°C) (1:
50) as the eluent to give 1.65 g (27%) of 6a (colorless oil) and
2.652 g (43%) of 7a (colorless oil). 6a : [R]25D: -9.3° (c, 2.66,
acetone); 1H NMR (CDCl3) δ 0.83 (s, 3 H), 0.84 (s, 3 H), 1.0 (s,
3 H), 1.50-1.70 (m, 4 H), 2.0 (s, 1 H), 2.02 (s, 1 H), 3.21 (m, 1
H), 3.29 (d, J ) 3.80 Hz, 1 H), 3.71 (d, J ) 13.19 Hz, 1 H),
3.78 (d, J ) 13.21 Hz, 1 H), 7.19-7.37 (m, 5 H); MS m/ z 276
(M+, 14), 258 (3), 185 (66), 167 (12), 157 (21), 153 (3), 136 (12),
123 (61), 109 (20), 95 (44), 91 (100), 83 (25), 65 (14), 55 (23),
43 (20). 7a : [R]25D: +5.5° (c, 1.81, acetone); 1H NMR (CDCl3)
δ 0.87 (s, 9 H), 1.15 (m, 1 H), 1.47 (m, 2 H), 1.74 (m, 1 H), 1.80
(d, J ) 4.0 Hz, 1 H), 2.77 (s, br, 1 H), 3.42 (m, 1 H), 3.68 (m,
2 H), 3.74 (dd, J ) 9.19, 1.49 Hz, 1 H), 7.22-7.30 (m, 5 H);
MS m/ z 276 (M+, 11), 258 (5), 185 (65), 167 (14), 157 (29), 153
(3), 136 (13), 123 (73), 109 (22), 95 (23), 91 (100), 83 (20), 81
(19), 65 (14), 55 (18), 43 (17).
example of opposite asymmetric induction in a reaction
with two types of reagents prepared through a slight
change in reaction conditions from the same chiral
starting material. All epoxidation reactions were run
under solid-liquid phase-transfer condition with solid
KOH as the base in acetonitrile at room temperature in
one pot. No moisture-free and oxygen-free manipulations
were required.
Exp er im en ta l Section
Ma t er ia ls a n d Gen er a l P r oced u r e. D-(+)-Camphor
(>98.0%, mp 178 °C) was obtained from Tokyo Kasei Kogyo
Co., LTD, and was used directly in our reactions. All other
reagents and solvents, unless otherwise specified, were bought
from commercial suppliers and used without further purifica-
tion. THF was distilled from sodium/benzophenone ketyl
under nitrogen. The CH2Cl2 was dried over CaH2 and distilled
under nitrogen atmosphere. Proton magnetic resonance spec-
tra, including 1H-1H NOESY, were recorded on a 300 MHz
spectrometer. S-Benzyl benzenethiolsulfonate (yield: 95%, mp
42-43 °C) and S-methyl benzenethiolsulfonate (yield: 68%,
colorless oil) were prepared according to a literature method.16
The syntheses of sulfides 2a (yield: 88%, mp 72-75 °C, [R]D:
+126° (c, 2.88, acetone)), 2b (yield: 83%, [R]D: +92.7° (c, 2.34,
acetone)), 3a (yield: 92%, [R]D: -8.7° (c, 2.79, acetone)), 3b
(yield: 82%, [R]D: +7.52° (c, 2.12, acetone)), 5a (yield: 83%,
[R]D: -30.2° (c, 1.08, acetone), HRMS cacld for C17H22OS (M+)
274.1391: found: 274.1401), and 5b (yield: 85%, [R]D: +53.3°
(c, 2.85, acetone), HRMS cacld for C11H18OS (M+) 198.1078:
found: 198.1059) were performed using Haynes’ method.10
(-)-(1R ,2S )-2-M e t h o x y -exo-3-(b e n z y lt h i o )-1,7,7-
tr im eth ylbicyclo[2.2.1]h ep ta n e (4a ). A reaction tube con-
taining a magnetic stirring bar was placed with 306 mg (1.1
mmol) of 3a 10 and 4 mL of THF. Sodium hydride (55% in oil,
58 mg, 1.32 mmol) was added subsequently at room temper-
ature under N2. After stirring for 15 min, MeI (0.1 mL, 1.5
mmol) was introduced through a syringe into this reaction
mixture. The reaction was worked up after 30 min with the
addition of 3 g of silica gel GF254 to destroy excess NaH.
Chromatography of the product followed on a silica gel column
with an eluent of ethyl acetate/petroleum ether (60-90 °C)
(+)-(1R,2R)-en do-3-(Meth ylth io)-1,7,7-tr im eth ylbicyclo-
[2.2.1]h ep ta n -2-ol (6b) a n d (+)-(1R,2S)-en d o-3-(Meth yl-
th io)-1,7,7-tr im eth ylbicyclo[2.2.1]h ep ta n -2-ol (7b). Pre-
pared as described for the preparation of 6a and 7a . From
9.359 g (47.0 mmol) of 5b10 was obtained 2.988 g (32%) of 6b
(colorless oil) and 5.840 g (62%) of 7b (colorless, oil). 6b: [R]25
:
D
+22.2° (c, 3.16, acetone); 1H NMR (CDCl3) δ 0.88 (s, 3 H),
0.90 (s, 3 H), 0.94 (s, 3 H), 1.2 (m, 1 H), 1.45 (m, 2 H), 1.74 (m,
1 H), 1.90 (t, J ) 4.27 Hz, 1 H), 2.06 (s, 3 H), 2.94 (s, br., 1 H),
3.39 (m, 1 H), 3.82 (dd, J ) 9.24, 2.02 Hz, 1 H); MS m/ z 200
(M+, 47), 185 (13), 183 (4), 172 (93), 157 (29), 153(8), 124 (89),
109 (100), 95 (71), 90 (71), 83 (71), 69 (45), 55 (36), 43 (40).
1
7b: [R]25D: +15.6° (c, 2.04, acetone); H NMR (CDCl3) δ 0.88
(s, 6 H), 1.08 (s, 3 H), 1.53 (m, 2 H), 1.71-1.84 (m, 3 H), 1.91
(s, br., 1 H), 2.12 (s, 3 H), 3.22 (m, 1 H), 3.31 (d, J ) 3.84 Hz,
1 H); MS m/ z 201 (M+ + 1, 29), 200 (M+, 91), 183 (23), 172
(36), 157 (20), 152 (36), 137 (26), 124 (70), 109 (87), 95 (100),
90 (72), 83 (89), 69 (45), 55 (67), 43 (50).
Gen er a l P r oced u r e for Stoich iom etr ic En a n tioselec-
t ive E p oxid a t ion . A reaction tube containing a magnetic
stirring bar was charged with sulfides 3a , 4a , 6a , or 7a (1
mmol), aldehyde (1.2 mmol), MeI (2 mmol), powdered potas-
sium hydroxide (2 mmol), and CH3CN (4 mL). After stirring
for 30 h, the reaction was completed according to TLC. The
reaction mixture was then filtered on a short silica gel column
to remove inorganic salts. The filtrate was concentrated, and
the residue was purified by preparative TLC with a mixture
of petroleum ether (60-90 °C) and ethyl acetate (90:10) as the
eluent to give pure trans-diaryloxiranes 10.
(1:20) gave 311 mg (97%) of 4a as a colorless oil: [R]25
:
D
-102.6° (c, 1.91, acetone); 1H NMR (CDCl3) δ 0.76 (s, 3 H),
0.88 (s, 3 H), 1.13 (s, 3 H), 0.93, 0.96, 1.45, 1.66 (m, 4 H), 1.74
(d, J ) 3.77 Hz, 1 H), 2.82 (d, J ) 7.67 Hz, 1 H), 3.08 (d, J )
7.82 Hz, 1 H), 3.37 (s, 3 H), 3.72 (m, 2 H), 7.22-7.33 (m, 5 H);
MS m/ z 290 (M+, 8), 259 (23), 199 (100), 167 (27), 135 (20),
123 (34), 91 (73), 85 (21), 73 (9), 55 (16), 45 (14); HRMS cacld
for C18H26OS (M+) 290.1704, found 290.1679.
tr a n s-2-P h en yl-3-p h en yloxir a n e (10a ): mp 67-69 °C
1
(lit.15 69 °C); H NMR (CDCl3) δ 3.86 (s, 2 H), 7.29-7.40 (m,
10 H).
tr a n s-2-(p-Ch lor op h en yl)-3-p h en yloxir a n e (10b): mp
1
98-99 °C (lit.15 100 °C); H NMR (CDCl3) δ 3.79 (d, J ) 1.9
(-)-(1R ,2S )-2-M e t h o x y -exo-3-(m e t h y lt h i o )-1,7,7-
t r im et h ylb icyclo[2.2.1]h ep t a n e (4b ). Prepared as de-
scribed for the preparation of 4a . From 301 mg (1.5 mmol) of
Hz, 1 H), 3.82 (d, J ) 1.7 Hz, 1 H), 7.21-7.37 (m, 9 H).
tr a n s-2-(p-Tolyl)-3-p h en yloxir a n e (10c): mp 60-62 °C
(lit.15 62 °C); 1H NMR (CDCl3) δ 2.36 (s, 3 H), 3.82 (d, J ) 1.8
Hz, 1 H), 3.84 (d, J ) 1.8 Hz, 1 H), 7.16-7.38 (m, 9 H).
Gen er a l P r oced u r e for Ca t a lyt ic E n a n t ioselect ive
Ep oxid a tion . A reaction tube containing a magnetic stirring
bar was charged with sulfides 3b, 4b, 6b, or 7b (0.2 mmol),
aldehyde (1.0 mmol), benzyl bromide (1.2 mmol), powdered
potassium hydroxide (2.0 mmol), and CH3CN (4 mL). After
stirring for 15-20 h, the reaction was completed according to
TLC. The reaction mixture was then filtered on a short silica
gel column to remove inorganic salts. The filtrate was
concentrated and the residue was purified by preparative TLC
with a mixture of petroleum ether (60-90 °C) and ethyl acetate
(90:10) as the eluent to give pure trans-diaryloxiranes 10.
3b10 was obtained 354 mg (79%) of 4b as a colorless oil: [R]25
:
D
-90.6° (c, 2.46, acetone); 1H NMR (CDCl3) δ 0.78 (s, 3 H),
0.91 (s, 3 H), 1.13 (s, 3 H), 1.47-1.55 (m, 2 H), 1.72-1.77 (m,
2 H), 1.83 (d, J ) 3.98 Hz, 1 H), 2.12 (s, 3 H), 2.88 (d, J ) 7.74
Hz, 1 H), 3.20 (d, J ) 7.72 Hz, 1 H), 3.44 (s, 3 H); MS m/ z 214
(M+, 78), 199 (36), 183 (100), 167 (55), 151 (25), 135 (90), 121
(26), 104 (50), 95 (29), 85 (67), 55 (37); HRMS (EI) calcd for
C12H22OS (M+) 214.1391, found 214.1376.
(-)-(1R,2R)-en d o-3-(Ben zylth io)-1,7,7-tr im eth ylbicyclo-
[2.2.1]h eptan -2-ol (6a) an d (+)-(1R,2S)-en do-3-(Ben zylth io)-
1,7,7-tr im eth ylbicyclo[2.2.1]h ep ta n -2-ol (7a ). Diisobutyl-
aluminum hydride (DIBAL-H, 2.5 M in toluene, 14.3 mL) was
introduced through a syringe into a solution of 6.175 g (22.5
mmol) of 5a 10 in 100 mL of CH2Cl2 under N2 at room
temperature. After stirring for 30 min, the reaction mixture
was cautiously poured into 360 mL of saturated aqueous NH4-
Cl. The organic phase was separated, and the aqueous phase
was extracted with ether (3 × 240 mL). The organic phases
were combined and washed sequentially with 3 M HCl (3 ×
240 mL) and saturated NaHCO3 (3 × 240 mL), dried over
Ack n ow led gm en t. Financial supports from the
National Natural Foundation of China and Chinese
Academy of Sciences are gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (14 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(15) Imuta, M; Ziffer, H. J . Org. Chem. 1979, 44, 2505-2509.
(16) Hayashi, S.; Furukawa, M.; Yamamoto, J .; Niigata, K. Chem.
Pharm. Bull. 1967, 15, 1188-1192.
J O951442+