A systematic study on the use of different organocatalytic activation modes for asymmetric conjugated addition reactions of isoindolinones

In this article we describe a series of new asymmetric Michael reactions of carboxylate-3-substituted isoindolinones used as nucleophiles in the synthesis of valuable chiral tetrasubstituted derivatives. It has been shown that the reactivity and enantioselectivity strongly depend on the substitution pattern of the isoindolinone, requiring either cinchona-alkaloid based phase transfer catalysts or bifunctional tertiary amines organocatalysts. Moreover, prolinol-TMS ether-based secondary amine catalysts permitted the development of Michael/cyclization tandem reaction with cynnamaldehyde for the synthesis of azapolycyclic derivatives. (C) 2016 Elsevier Ltd. All rights reserved.