Chiral aliphatic amines are privileged functionalities in pharmaceutical molecules and play an essential role as ligands and catalysts in organic synthesis. It is therefore important to develop efficient catalytic strategies to access aliphatic amines in an enantiopure form. Despite great advancement in asymmetric amination methods, including reductive amination and C–N cross coupling, direct access to diverse enantioenriched aliphatic amines from readily available feedstocks is still lacking. Herein, we demonstrate direct enantioconvergent amination of racemic secondary alcohols using a variety of aliphatic primary amines, under the cooperative catalysis of a chiral iridium complex with a chiral phosphoric acid. This strategy realizes a challenging catalytic redox-neutral cascade without the need for any stoichiometric reagent, offering a one-step conversion of feedstock substrates to valuable chiral aliphatic secondary amines in high yield and enantioselectivity. The use of this atom-economical carbon–nitrogen bond-forming strategy is illustrated by the enantioselective synthesis of commercial drugs and their analogues. Futhermore, we discovered an intriguing racemization pathway for chiral aliphatic amines, which delivers important guiding principles for redox-related stereoselective control in chiral amine synthesis.
Preparing enantioenriched aliphatic amines from readily available feedstocks is challenging to achieve. Now, direct enantioconvergent amination of racemic secondary alcohols using a variety of aliphatic primary amines is reported, catalysed by chiral iridium and phosphoric acid species. This atom-economical strategy streamlines the enantioselective synthesis of N-containing commercial drugs and analogues.