Synthesis of chiral epoxides from aldehydes using sulfur ylide derived from reduced product of bakers' yeast reduction

Article abstract of DOI:10.1055/s-1999-2830

Enantiomerically pure β-hydroxy ester derivatives possessing a sulfide group were obtained in the bakers' yeast reduction of the corresponding β- keto esters in the presence of a sulfur compound as an additive. Highly enantioselective synthesis of epoxides from aldehydes was achieved using sulfur ylide derived from chiral I β-hydroxy esters.

Full text of DOI:10.1055/s-1999-2830

1
328
LETTER
Synthesis of Chiral Epoxides from Aldehydes Using Sulfur Ylide Derived from
Reduced Product of Bakers’ Yeast Reduction
Ryuuichirou Hayakawa, Makoto Shimizu*
Department of Chemistry for Materials, Mie University, Tsu, Mie 514-8507, Japan
Received 31 May 1999
ester analogues, involving some modification of the sub-
strate, addition of an additive as a selective inhibitor of
Abstract: Enantiomerically pure b-hydroxy ester derivatives pos-
3
sessing a sulfide group were obtained in the bakers’ yeast reduction
4
5
reductase, addition of an inorganic salt, immobilization
of the corresponding b-keto esters in the presence of a sulfur com-
6
7
pound as an additive. Highly enantioselective synthesis of epoxides of bakers’ yeast, thermal treatment of bakers’ yeast, or
8
from aldehydes was achieved using sulfur ylide derived from chiral use of an organic solvent. ꢀ We have developed an effec-
b-hydroxy esters.
tive method for enhancement of the reactivity and enanti-
Key words: bakers’ yeast, sulfur compound, chiral sulfide, sulfur oselectivity in the bakers’ yeast reduction using a sulfur
9
ylide, epoxidation
compound as an additive. In this report, the bakers’ yeast
reduction of b-keto esters possessing sulfide in the pres-
ence of a sulfur compound was investigated, and the cor-
responding reduced products were applied to synthesis of
epoxides from aldehyde derivatives.
Optically active epoxide is a useful synthetic intermediate
of natural products. Synthesis of epoxide from aldehyde
using chiral sulfide as a catalyst is one of the effective
methods for the preparation of optically active epoxides.1
A number of sulfide reagents have been used as a catalyst.
However, the preparation of the sulfide needed multiple
steps, because chiral sulfide is not readily available in nat-
ural products. On the other hand, bakers’ yeast reduction
is a useful method for preparation of optically active alco-
2
-Methoxycarbonyltetrahydrothiophen-3-one 1 and 3-
metoxycarbonyl-tetrahydrothiopyran-4-one 2 were used
as substrates. In terms of the structure of sulfur ylide,
transformation of the ester moiety into diphenyl carbinol
followed by ketalization with the other hydroxy group de-
rived from the yeast reduction may make a suitable envi-
ronment for the epoxidation of aldehydes via ylide
formation in an enantioselective manner. Although the
bakers’ yeast reductions of 2-methoxycarbonyl-tetrahy-
drothiophen-3-one 1 and 3-metoxycarbonyltetrahydrothi-
opyran-4-one 2 have already been reported, the
enantioselectivity was not satisfactory.10 Therefore, the
bakers’ yeast reduction of those substrate in the presence
2
hols. However, there have been examples that afforded
unsatisfactory results, low chemical yield, and/or low se-
lectivity, mainly because of the participation of multiple
enzymes with different enantioselectivity. A number of
methods have been reported for the improvement of the
enantioselectivity of the bakers’ yeast reduction of b-keto
O
OH
CO2Me
)n
CO Me
2
BY, Sulfur Compound
EtOH, Solvent
(
( )n
S
S
1
2
; n = 0
; n = 1
3; n = 0
4; n = 1
Synlett 1999, No. 8, 1328–1330 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Synthesis of Chiral Epoxides from Aldehydes Using Sulfur Ylide
1329
of a sulfur compound was investigated. In a typical proce- In a typical procedure of synthesis of epoxides, 0.4 mL of
dure of the bakers’ yeast reduction, a suspension of 2.82 g acetonitrile solution of the chiral sulfide (0.11 mmol) was
of dry bakers’ yeast (S. I. Lesaffre) in 28 mL of dist. H O stirred at 0 °C. To the solution was added 2 equiv of ben-
2
was stirred for 0.5 h at ambient temperature. To the result- zylbromide. After 10 min. stirring, 0.44 mL of an acetoni-
ing suspension was added L-cysteine (342 mg, 2.82 trile solution of 2 equiv of aldehyde and powder of 2.8
mmol). After 0.5 h stirring, 2.8 mL of an ethanol solution equiv of NaOH were added at the same temperature. The
of 2-methoxycarbonyltetrahydrothiophen-3-one (150 mg, reaction temperature was allowed to rise to ambient tem-
0
.94 mmol) was added to the suspension of bakers’ yeast perature. The reaction was quenched by addition of brine.
at 0 °C. After 7.0 h stirring, Celite and ethyl acetate were The resulting mixture was extracted with ethyl acetate (15
added to the reaction mixture, and the whole mixture was mL x 3). The combined organic extracts were dried over
stirred for 0.5 h. The resulting mixture was filtered anhydrous Na SO and concentrated in vacuo. The resi-
2
4
through a Celite pad. The filtrate was extracted with ethyl due was purified on preparative TLC. The results are sum-
acetate (3 x 30 mL). The combined organic extracts were marized in Table 2.
dried over anhydrous Na SO and concentrated in vacuo.
2
4
Synthesis of epoxide from benzaldehyde using sulfur
ylide derived from chiral sulfide 6 gave (R,R)-stilbene ox-
ide in 64% yield, while the enantioselectivity was only 7%
ee. The absolute configuration was established by com-
parison of the optical rotation with an authentic sample.
The low selectivity may be due to the distance of the chiral
center to the reaction point. Therefore, tetrahy-
drothiophene derivative 5 was used as a catalyst instead of
the tetrahydrothiopyrane derivative. The enantioselectivi-
ty was increased with up to 78% ee. The turnover cycle for
the reaction of benzaldehyde was observed using NaOH
as a base, which has not been previously reported without
The residue was purified by flash chromatography. The
bakers’ yeast reduction of b-keto esters was investigated,
and the results are summarized in Table 1. Diastereomer-
ically pure reduced product 3 was obtained in the bakers’
yeast
reduction
of
2-methoxycarbonyltetrahy-
drothiophen-3-one 1 with 96% ee, while the chemical
yield was low because of the low stability under the reac-
tion conditions (Entry 1). The absolute configuration was
established by comparison of the optical rotation with re-
ported data. Therefore, dist. H O was used as a solvent.
The bakers’ yeast reduction in the presence of a sulfur
1
0
2
compound such as L-cysteine or DMSO was investigated
Entries 3 & 4). However, the enantioselectivity was not
1a
using excess aldehyde (Entry 3). Benzyl benzoate was
(
produced via Cannizzarro reaction of benzaldehyde using
KOH as a base. The reaction with various aldehydes was
investigated under the same conditions. Increased enanti-
oselectivity was observed by introduction of a chloro
group to the ortho-position of benzaldehyde (Entry 5).
The highest enantioselectivity was achieved in the reac-
tion of tolaldehyde with up to 92% ee (Entries 6 & 7).
increased, which may be due to the high reactivity of the
reduction. Accordingly reaction temperature was investi-
gated. Enantioselectivity was improved at 0 °C, while the
yield was low. The enantiomeically pure reduced product
was obtained in 59% yield using L-cysteine as an additive
at 3-14 °C (Entry 7). The bakers’ yeast reduction of 3-
methoxycarbonyl-tetrahydrothiopyran-4-one
gave
(
3R,4S)-4-hydroxy-3-methoxy-carbonyltetrahydrothio-
pyrane with 92% ee. Improved enantioselectivity and ac-
celeration of the reactivity were observed using 3 eq of
DMSO as an additive with up to >99% ee (Entry 9). These
reduced products obtained with enantiomerically pure
form was transformed to apply to epoxidation of alde-
hydes as a catalyst as follows. Diphenyl carbinol was ob-
tained by diphenylation of the ester, which was ketalized
with 2,2-dimethoxypropane.
Sulfide Reagent (1.0 eq)
BnBr (4.0 eq)
O
RCHO (2.0 eq)
Ph
R
Base ( 2.8 eq) / CH CN
3
MeO OMe
OH
O
PhLi
O
CO2Me
S
3
Et2O
CSA / acetone
Y. 85%
S
Ph
Ph
Y. 88%
5
OH
O
S
O
MeO OMe
CO2Me
PhLi
Ph
Ph
In conclusion, homo chiral sulfide derivatives were easily
synthesized utilizing the bakers’ yeast reduction in the
presence of a sulfur compound. Subsequent manipulation
of the reduction products allows a highly enantioselective
Et2O
CSA / acetone
Y. 86%
S
4
Y. 70%
6
Synlett 1999, No. 8, 1328–1330 ISSN 0936-5214 © Thieme Stuttgart · New York

1
330
R. Hayakawa, M. Shimizu
LETTER
synthesis of epoxides from aldehydes without tedious iso-
lation of intermediary sulfur ylides.
Tetrahedron Lett. 1990, 31, 267. Ushio, K.; Hada, J.; Tanaka,
Y.; Ebara, K. Enzyme Microb. Technol. 1993, 15, 222.
5) Nakamura, K.; Kawai, Y.; Oka, S.; Ohno, A. Tetrahedron
Lett. 1989, 30, 2245.
(
References and Notes
(6) Nakamura, K.; Higaki, M.; Ushio, K.; Oka, S.; Ohno, A.
Tetrahedron Lett. 1985, 26, 4213. Naoshima, Y.; Hasegawa,
H. Chem. Lett. 1987, 2379.
(
(
1) (a) Furukawa, N.; Sugihara, Y.; Fujihara, H. J. Org. Chem.
989, 54, 4222. (b) Breau, L.; Ogilvie, W. W.; Durst, T.
1
(
7) Nakamura, K.; Kawai, Y.; Nakajima, N.; Ohno, A. J. Org.
Chem. 1991, 56, 4778. Nakamura, K.; Kawai, Y.; Ohno, A.
Tetrahedron Lett. 1991, 32, 2927. Kawai, Y.; Kondo, S.;
Tsujimoto, M.; Nakamura, K.; Ohno, A. Bull. Chem. Soc. Jpn.
Tetrahedron Lett. 1990, 31, 35. (c) Breau, L.; Durst, T.
Tetrahedron Asymm. 1991, 2, 367. (d) Aggarwal, V. K.;
Kalomiri, M.; Thomas, A. P. Tetrahedron: Asymmetry 1994,
5
, 723. (e) Solladié-Cavallo, A.; Diep-Vohuule, A. J. Org.
1994, 67, 2244.
Chem. 1995, 60, 3494. (f) Li, A. -H.; Dai, L. -X.; Hou, X. -L.;
Huang, Y. -Z.; Li, F. -W. J. Org. Chem. 1996, 61, 489.
2) Servi, S. Synthesis 1990, 1. Csuk, R.; Glänzer, B. I. Chem.
Rev. 1991, 91, 49. Jones, J. B. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: New York,
(
8) Jayasinghe, L. Y.; Smallridge, A. J.; Trewhella, M. A.
Tetrahedron Lett. 1993, 34, 3949. North, M. Tetrahedron Lett.
1996, 37, 1699. Rotthaus, O.; Krüger, D.; Demuth, M.;
Schaffner, K. Tetrahedron 1997, 53, 935. Medson, C.;
Smallridge, A. J.; Trewhella, M. A. Tetrahedron: Asymmetry
1991, 8, p 183. Santaniello, E.; Ferraboshi, P.; Grisenti, P. In
1997, 8, 1049.
Encyclopedia of reagents for Organic Synthesis; Paquet, L.
A., Ed.; John Wiley & Sons; Chichester, 1995, 1, p 233.
3) Zhou, B.; Gopalan, A. S.; Middlesworth, F. V.; Shieh, W. -R.;
Sih, C. J. J. Am. Chem. Soc. 1983, 105, 5925. Fuganti, C.;
Grasselli, P.; Casati, P.; Carmeno, M. Tetrahedron Lett. 1985,
(
9) Hayakawa, R.; Nozawa, K.; Shimizu, M.; Fujisawa, T.
Tetrahedron Lett. 1998, 39, 67. Hayakawa, R.; Shimizu, M.;
Fujisawa, T. Tetrahedron: Asymmetry 1997, 8, 3201.
(
(
(
10) Hoffmann, R. W.; Helbeg, W.; Ladner, W. Tetrahedron Lett.
982, 23, 3479.
1
26, 101.
4) Nakamura, K.; Inoue, K.; Ushio, K.; Oka, S.; Ohno, A. Chem.
Lett. 1987, 679. Nakamura, K.; Kawai, Y.; Ohno, A.
Article Identifier:
437-2096,E;1999,0,08,1328,1330,ftx,en;Y11499ST.pdf
1
Synlett 1999, No. 8, 1328–1330 ISSN 0936-5214 © Thieme Stuttgart · New York