Origin of the Enantioselectivity in Organocatalytic Michael Additions of [beta]-Ketoamides to [alpha],[beta]-Unsaturated Carbonyls: A Combined Experimental, Spectroscopic and Theoretical Study

The organocatalytic enantioselective conjugate addition of secondary [beta]-ketoamides to [alpha],[beta]-unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic ami...

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Bibliographic Details
Published in:	Chemistry : a European journal Vol. 21; no. 2; p. 778
Main Authors:	Quintard, Adrien, Cheshmedzhieva, Diana, SanchezDuque, Maria del Mar, Gaudel-Siri, Anouk, Naubron, Jean-Valère, Genisson, Yves, Plaquevent, Jean-Christophe, Bugaut, Xavier, Rodriguez, Jean, Constantieux, Thierry
Format:	Journal Article
Language:	English
Published:	Weinheim Wiley Subscription Services, Inc 07-01-2015
Subjects:	Chemistry
Online Access:	Get full text
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Summary:	The organocatalytic enantioselective conjugate addition of secondary [beta]-ketoamides to [alpha],[beta]-unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99%ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst.
ISSN:	0947-6539 1521-3765
DOI:	10.1002/chem.201404481