Iron-Catalyzed Enantioconvergent Amination of Alcohols

Abstract

Owing to the prevalence of chiral amines in natural products and pharmaceuticals, we developed an iron-catalyzed borrowing hydrogen enantioconvergent amination of alcohols in the presence of chiral phosphoric acid. This protocol effectively converts a range of secondary alcohols and amines, tolerating numerous functional groups, including hydroxyl, cyano, ester, and boronate groups, into chiral amines with high to excellent yields (up to 99%) and enantioselectivities (up to 99% ee). Notably, the compatibility with peptides, including di- and tripeptides, offers new possibilities for exploring chemical transformations in biological contexts. Mechanistic studies revealed a hydrogen-borrowing pathway, with DFT calculations further elucidating the crucial role of the chiral environment (pocket) in controlling enantioselectivity.

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