Chiral Aldehyde Catalysis Enables Asymemtric Synthesis Of 1,2-Diaryletheylene Amines And α-Alkyl Tryptophan Derivatives

In the past several decades,great achievments have been made in the aldehyde-catalysed functionalization of amines.Among them,chiral aldehyde catalysis based on the amine activation mode has gradually become an important synthetic strategy for achieving the asymmetricα-functional groupization of primary amines.Especially,the chiral aldehyde catalysts derived from binaphthols have been successfully applied in the direct asymmetricreactions ofα-alkylation,Micheal addition,Mannich addition,and aldol addition.Furthermore,with the utilization of chiral aldehyde/transition-metal combining catalysis,the direct asymmetricα-allylation,benzylation,and propargylation of NH₂-unprotected amino acid esters have been also achieved successively.In this thesis,a chiral aldehyde-catalyzed Mannich reaction of benzylamine compound and aldeimines,and a chiral aldehyde/palladium combining catalysis enabled asymmetric cascade Heck-alkylation reaction was disclosed,leading to optically active 1,2-diaryletheylene amine with moderate yield and stereoselectivities and otptically active tryptophan derivatives with good-to-high yields and high-to-excellent enantioselectivities.This dissertation consists of three chapters.In the first chapter,we review the research background of chiral aldehydes catalysis and introduce the evolution of chiral aldehydes catalysis in the past decade.In the second chapter,we investigate the Mannich reaction of benzylamine compounds with imines catalyzed by chiral aldehydes.By systematic optimization of reaction conditions,we can construct 1,2-diarylethylenediamine with 75%yield,77:23 diastereoselectivity and 87%/97%selectivity.In the third chapter,we used a ternary catalysis system,combining chiral aldehydes with transition metals palladium and Lewis acid to realize the asymmetric Heck-alkylation tandem reactions of N-dienylarylamine derivatives and N-unprotected amino acid esters.After determining the optimum reaction conditions,a variety of unnatural optically active tryptophan derivatives are obtained with good-to-excellent yields and enantioselectivities.At the same time,we use this asymmetric catalytic method to synthesizeβ-carboline alkaloids.According to control experiments and existing literature reports,we propose a possible catalytic cycle process.