Synthesis of chiral β-arylamines via diastereoselective addition of aryl hydrazones to imines

Chiral β -arylamines could serve as key building blocks for the pharmaceutical industry and synthetic chemistry. Herein, we have developed methods for their synthesis via diastereoselective addition of hydrazones to N -( tert -butanesulfinyl)imines. Using a simple iron complex as a catalyst, aryl hydrazones add to both aryl and alkyl imines, affording chiral amines with broad substrate scope and excellent diastereoselectivities (47 examples, up to 99:1 dr ). Furthermore, a ruthenium-catalyzed addition of aryl hydrazones to α -branched imines derived from racemic aldehydes via dynamic kinetic resolution (DKR) has been developed to give chiral amines with two contiguous chiral centers with good stereoselectivities (34 examples, up to 97:3 dr , 99:1 er ). The chiral amine products can be readily converted to high-value chiral primary amines and serve as versatile synthetic intermediates for the synthesis of drugs and nitrogen-containing heterocycles, and notably, the absolute configuration of the amine products can be inversed by a simple switch in the chirality of the sulfinyl auxiliary. Two catalytic protocols have been developed for the synthesis of chiral amines: an iron-catalyzed addition of hydrazones to N -( tert -butanesulfinyl)imines that delivers β -arylamines with excellent diastereoselectivities, and a ruthenium-catalyzed dynamic kinetic resolution (DKR) of α -branched imines affording amines with two contiguous chiral centers in high stereoselectivities. In both cases, the sulfinyl auxiliary could be readily removed under mild conditions to furnish valuable enantioenriched chiral primary amines.