Organocatalytic asymmetric transfer hydrogenation of imines

Abstract

The asymmetric organocatalytic transfer hydrogenation of imines can be accomplished in good yields with high enantioselectivities through the use of BINOL-derived phosphoric acids as catalysts and Hantzsch esters or benzothiazoles as the hydride source. The same method can also be applied to the enantioselective reduction of benzo-fused heterocycles, such as quinolines, benzoxazines, benzothiazines, benzoxazinones, quinoxalines, quinoxalinones and a limited number of pyridines containing electron-withdrawing groups. Cascade reactions involving multiple reductions and rearrangements have been reported as well as combinations of metal-catalysed reactions, such as gold-catalyzed hydroaminations of alkynes combined with the reduction of the ensuing enamine. Although turnover frequencies of the organocatalytic imine hydrogenations are still lower than those of metal-catalyzed hydrogenations, there are several advantages. Mild and environmentally friendly conditions as well as excellent selectivity make this method a valuable approach to enantiopure amine building blocks.