Carbene-Catalyzed Activation of Remote Nitrogen Atoms of (Benz)imidazole-Derived Aldimines for Enantioselective Synthesis of Heterocycles

Abstract

A new mode of carbene-catalyzed heteroatom activation and asymmetric reactions is disclosed. The reaction starts with addition of a carbene catalyst to a (benz)imidazole-derived aldimine substrate. Subsequent oxidation and proton transfer lead to the formation of a catalyst-bound triaza-diene as the key intermediate, in which the nitrogen atom at a site remote to the catalyst-substrate bond is activated. This unusual triaza-diene intermediate then undergoes highly enantioselective reactions with activated ketones through a concerted asynchronous pathway, as supported by mechanistic studies and preliminary density function theory calculation.

Keywords: N-heterocyclic carbene; heteroatom activation; heterocycles; imines; triaza-diene.