Transition Metal-catalyzed Direct Asymmetric Reductive Amination Of Ketones For The Synthesis Of Primary Amines And Their Derivatives

Chiral amines are widely existed in natural products and drugs.The efficient preparation of various chiral amines is a hot topic in modern organic chemistry.Transition metal-catalyzed reductive amination can directly convert ketones into chiral amines,which is one of the most efficient methods to construct chiral amines.In recent years,asymmetric reductive amination catalyzed by transition metals has aroused extensive attention and considerable progress has also been achieved.However,significant challenges,such as the lack of highly efficient catalytic system and limited substrate scope,remain to be solved.Thus,it is necessary to develop new catalytic systems for asymmetric reductive amination of ketones.At present,there are only scarce examples regarding the preparation of chiral primary amines via transition metal-catalyzed direct asymmetric reduction amination.Asymmetric reductive amination of ketones with simple ammonia source such as ammonia or ammonium salts remains to be an unsolved challenge.In order to solve this problem,this dissertation has mainly studied ruthenium-catalyzed asymmetric reduction amination reaction of simple ketones with ammonium salt and H₂,which includes the following sections:（1）The chiral bisphosphine ligated ruthenium complexes were used to catalyze asymmetric reductive amination of simple aryl alkyl ketones with ammonium salt as ammonia source.Under mild conditions,chiral amines can be prepared with broad substrate generality and excellent enantioselectivity（up to 98%）.（2）The asymmetric cascade reductive amination and ring-closing reaction of keto acids and esters has been studied.A ruthenium complex has been successfully identified to realize this reaction,allowing for a one-pot protocol for the asymmetric synthesis of important lactams with high yields and enantioselectivities.