Catalytic Intramolecular Reductive Amination Using Secondary Amines: Expanding Access to Chiral Tertiary Amine Heterocycles

An unprecedented intramolecular asymmetric reductive amination that employs secondary amines as the nitrogen source, an important and persistent challenge in reductive amination, has been developed. This breakthrough broadens the synthetic scope, enabling the efficient construction of chiral tertiary amine-containing heterocycles, a crucial class of chiral amines. A tailored ZhaoPhos-based diphosphine ligand, distinct from commercial diphosphines, in combination with an iridium precursor delivers excellent catalytic activity and enantioselectivity. The synthetic utility of this approach is highlighted by the concise and scalable enantioselective synthesis of nicotinic alkaloids with significant medicinal value.