Organocatalytic Asymmetric Synthesis of Trifluoromethylated Tetrahydrocarbazoles by a Vinylogous Michael/Aldol Formal [4+2] Annulation

Abstract

A new protocol for the organocatalytic asymmetric synthesis of highly functionalized tetrahydrocarbazoles has been developed based on a vinylogous Michael/aldol reaction sequence between 3-(trifluoroacetyl)-2-methyl-indoles and enals. This formal [4+2] annulation occurs by cooperative catalysis between an achiral Brønsted base and a chiral secondary amine organocatalyst to afford tetrahydrocarbazole products bearing three vicinal stereocenters, including a trifluoromethylated tetrasubstituted stereocenter, in excellent yields, diastereo- and enantioselectivities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim