epoxidation for allylic alcohols and Jacobsen-Katsuki epoxi-
dation for unfunctionalized olefins have opened a brand new
field in organic chemistry.4 At the same time, a spectacular
advancement of metal-free enantioselective organocatalysis has
appeared as a very potent chiral building blocks constructing
method.5 Up to now, many methods have been developed, and
the epoxidation has been accomplished by homogeneous and
heterogeneous catalysts.6,7 Yet, improvement of the stereose-
lectivity and substrate scope is apparently a challenge. Orga-
nocatalysis is gaining more and more importance in asymmetric
synthesis and has become a main focus of research in recent
years.8 Among various organocatalysts for enantioselective
reactions, L-proline and its derivatives are most attractive.9,10
4-Substituted-r,r-diaryl-prolinols Improve the
Enantioselective Catalytic Epoxidation of
r,â-Enones
Yawen Li,† Xinyuan Liu,‡ Yingquan Yang,† and
Gang Zhao*,†,‡
Department of Chemistry, UniVersity of Science and Technology
of China, Hefei, Anhui 230026, People’s Republic of China, and
Laboratory of Modern Synthetic Organic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Recently, a new methodology for the catalytic asymmetric
epoxidation of a wide variety of R,â-enones mediated by the
bifunctional organocatalyst R,R-diphenyl-L-prolinol 3a has been
reported by Lattanzi (Scheme 1).11a The epoxides have been
obtained in good yields and enantioselectivity (up to 80% ee)
by employing 30 mol % catalyst loading at room temperature.
Based on our experience in proline-type ligands design and
synthesis,10 in consideration of the proposed catalytic mechanism
ReceiVed August 26, 2006
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Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem.
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Shi, Yian. Acc. Chem. Res. 2004, 37, 488. (d) Yang, D. Tetrahedron 2006,
62, 6605.
(6) For recently excellent reviews on metal-based homogeneous or
heterogeneous systems-promoted asymmetric epoxidation of alkenes, see:
(a) Lane, B. S.; Burgess, K. Chem. ReV. 2003, 103, 2457. (b) Tse, M. K.;
Do¨bler, C.; Bhor, S.; Klawonn, M.; Ma¨gerlein, W.; Hugl, H.; Beller, M.
Angew. Chem., Int. Ed. 2004, 43, 5255. (c) Xia, Q.-H.; Ge, H.-Q.; Ye,
C.-P.; Liu, Z.-M.; Su, K.-X. Chem. ReV. 2005, 105, 1603. (d) McGarrigle,
E. M.; Gilheany, D. G. Chem. ReV. 2005, 105, 1563. (e) Rose, E.;
Andrioletti, B.; Zrig, S.; Quelquejeu-Etheve, M. Chem. Soc. ReV. 2005,
34, 573. (f) Ku¨hn, F. E.; Santos, A. M.; Herrmann, W. A. Dalton Trans.
2005, 2483.
(7) For selected reports on asymmetric epoxidations of alkenes, see: (a)
Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Zheng, J.-H.; Cheung,
K.-K. J. Am. Chem. Soc. 1996, 118, 491. (b) Yang, D.; Wang, X.-C.; Wong,
M.-K.; Yip, Y.-C.; Tang, M.-W. J. Am. Chem. Soc. 1996, 118, 11311. (c)
Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am.
Chem. Soc. 1997, 119, 2329. (d) Yang, D.; Wong, M.-K.; Yip, Y.-C.; Wang,
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120, 5943. (e) Nemoto, T.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc.
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M. J. Am. Chem. Soc. 2001, 123, 2725. (g) Nemoto, T.; Kakei, H.;
Gnanadesikan, V.; Tosaki, S.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
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H.; Tsuji, R.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127,
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Y. J. Org. Chem. 2006, 71, 1715.
To seek novel metal-free organic catalysts for epoxidation
with high stereoselectivity, a series of 4-substituted-R,R-
diaryl-prolinols were synthesized in four steps from trans-
4-hydroxyl-L-proline. These prolinol derivatives catalyzed
the asymmetric epoxidation of R,â-enones to give the
corresponding chiral epoxides in good yields and high
enantioselectivities under mild reaction conditions. Studies
of substituent effects on enantioselectivity revealed that steric
bulk and electronic effect promoted higher enantioselectivity,
and prolinol 8a was found to be the best catalyst until now.
Chiral epoxides are very important building blocks for the
synthesis of enantiomerically pure complex molecules, in
particular of biologically active compounds.1,2 The asymmetric
epoxidation of functionalized and unfunctionalized olefins has
emerged as a very versatile and important synthetic tool in
organic synthesis.3 Many asymmetric synthesis methods have
been developed to meet this purpose in the past years. In the
field of metal-catalyzed epoxidations, particularly, the Sharpless
* To whom correspondence should be addressed. Phone: 0086-21-54925182.
Fax: 0086-21-64166128.
† University of Science and Technology of China.
‡ Chinese Academy of Sciences.
(1) Smith, G. J. Synthesis 1984, 8, 629.
(2) Besse, P.; Veschambre, H. Tetrahedron 1994, 50, 8885.
(3) (a) Johnson, R. S.; Sharpless, K. B. In ComprehensiVe Organic
Synthesis; Trost, B. M., Flemming, I., Eds.; Pergamon Press: New York,
1991; Vol. 7, p 389. (b) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; John Wiley & Sons: New York, 1994. (c) Comprehensive
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: New York, 1999. (d) Catalytic Asymmetric Synthesis, 2nd ed.;
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tion, see: (a) List, B. Synlett 2001, 1675. (b) Jarvo, E. R.; Miller, S. J.
Tetrahedron 2002, 58, 2481. (c) Dalko, P. I.; Moisan, L. Angew. Chem.,
Int. Ed. 2004, 43, 5138. (d) Special Issue: Asymmetric Organocatalysis.
Acc. Chem. Res. 2004, 37, 487. (e) Seayad, J.; List, B. Org. Biomol. Chem.
2005, 3, 719.
10.1021/jo0617619 CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/10/2006
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