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The Use of N ‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins
Author(s) -
Andrey Olivier,
Alexakis Alexandre,
Tomassini Axel,
Bernardinelli Gerald
Publication year - 2004
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200404037
Subject(s) - chemistry , michael reaction , aldehyde , adduct , ketone , alkyl , catalysis , enamine , organocatalysis , medicinal chemistry , organic chemistry , hydrogen bond , enantioselective synthesis , molecule
The direct Michael addition of aldehydes and ketones to nitroolefins, catalyzed by N‐i‐ Pr‐2,2′‐bipyrrolidine, is described. The desired 1,4‐adducts are obtained in excellent yields with enantioselectivities up to 95% ee and dr up to 95 : 5 of the syn aldehyde addition product. An unexpected inversion of diastereoselectivity was observed for the addition of α‐hydroxy ketones to β‐arylnitroolefins with enantioselectivities up to 98% ee. The formation of an internal hydrogen bond between the OH group of the α‐hydroxy ketone and the tertiary nitrogen of the catalyst leads to the formation of a rigid cis enamine intermediate that accounts for the inversion of the expected diastereoselectivity and the very high ees.