One-pot organocatalytic domino Michael-aldol and intramolecular SN2 reactions.: Asymmetric synthesis of highly functionalized epoxycyclohexanone derivatives

被引:164
作者
Marigo, M [1 ]
Bertelsen, S [1 ]
Landa, A [1 ]
Jorgensen, KA [1 ]
机构
[1] Aarhus Univ, Ctr Catalysis, Dept Chem, Danish Natl Res Fdn, DK-8000 Aarhus C, Denmark
关键词
D O I
10.1021/ja058490o
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The development of the organocatalytic asymmetric one-pot Michael-Darzens condensation giving highly functionalized complex epoxycyclohexanone derivatives with up to four chiral centers is presented. Depending on the reaction conditions, either the polysubstituted 7-oxa-bicyclo[4.1.0]heptan-2-one ring system or 2-chloro-cyclohex-2-enone derivatives can be formed. For the former class of compounds a high diversity in substitution pattern is demonstrated, and the optically active products are obtained in excellent diastereo- and enantioselectivities. The potential synthetic applications of the products have been demonstrated by performing a series of highly diastereoselective transformations leading to optically active products useful for the life-science industry. Furthermore, mechanistic investigations on the formation of the chiral centers in the optically active epoxycyclohexanone are presented.
引用
收藏
页码:5475 / 5479
页数:5
相关论文
共 46 条
[1]   Highly enantioselective Darzens reaction of a camphor-derived sulfonium amide to give glycidic amides and their applications in synthesis [J].
Aggarwal, VK ;
Hynd, G ;
Picoul, W ;
Vasse, JL .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (34) :9964-9965
[2]   Phase-transfer-catalyzed asymmetric Darzens reaction [J].
Arai, S ;
Shirai, Y ;
Ishida, T ;
Shioiri, T .
TETRAHEDRON, 1999, 55 (20) :6375-6386
[3]   A NEW SYNTHETIC ROUTE TO FUNCTIONALIZED 2-AZABICYCLO[2.2.2]OCTANE [J].
ASAOKA, M ;
OHKURA, N ;
YOKOTA, M ;
SONODA, S ;
TAKEI, H .
HETEROCYCLES, 1994, 38 (11) :2455-2462
[4]  
Berkessel A, 2005, ASYMMETRIC ORGANOCATALYSIS: FROM BIOMIMETIC CONCEPTS TO APPLICATIONS IN ASYMMETRIC SYNTHESIS, P1, DOI 10.1002/3527604677
[5]   A proline-catalyzed asymmetric Robinson annulation reaction [J].
Bui, T ;
Barbas, CF .
TETRAHEDRON LETTERS, 2000, 41 (36) :6951-6954
[6]   Diphenylprolinol methyl ether: A highly enantioselective catalyst for Michael addition of aldehydes to simple enones [J].
Chi, YG ;
Gellman, SH .
ORGANIC LETTERS, 2005, 7 (19) :4253-4256
[7]   In the golden age of organocatalysis [J].
Dalko, PI ;
Moisan, L .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (39) :5138-5175
[8]  
EDER U, 1971, ANGEW CHEM, V83, P492
[9]   A general organocatalyst for direct α-functionalization of aldehydes:: Stereoselective C-C, C-N, C-F, C-BR, and C-S bond-forming reactions.: Scope and mechanistic insights [J].
Franzén, J ;
Marigo, M ;
Fielenbach, D ;
Wabnitz, TC ;
Kjaersgaard, A ;
Jorgensen, KA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (51) :18296-18304
[10]  
Frisch M. J., 2004, GAUSSIAN 03 REVISION