Chiral Aldehyde/Palladium Combining Catalysis Enables Asymmetric Synthesis Of α,α-disubstituted Amino Acid Esters

Chiral aldehyde catalysis based on imine activation mode has gradually become a powerful and highly efficient synthesis strategy for achieving the asymmetricα-functionalization of primary amine compounds.One hand,chiral aldehydes have been reported good organocatalysts which can promote the asymmetric reactions of alkylation,Mannich,Aldoland Michael additions.On the other hand,with the utilization of chiral aldehyde/transition-metal combining catalysis,the asymmetric allylation,benzylation,and alkynylation of primary amines have been successfully achieved.However,all of the reported chiral aldehyde/transition-metal catalysis are merely used to construct a single carbon chiral center in one reaction and rely on the use of leaving-group-contained functionalization reagents.In this thesis,we employed the chiral aldehyde/transition-metal catalysis for constructing optically active unnatural amino acid bearing two adjecent chiral centers,and to promote a completely atom-economicalα-allylation reaction of NH₂-unprotected amino acid esters with allenes.This dissertation consists of three chapters:The first chapter is a literature review.We have introduced chiral aldehyde catalysis from two aspects,including the chiral aldehyde organocatalysis and the chiral aldehyde/transition-metal combining catalysis.In chapter 2,the asymmetricα-allylation of amino acid esters with 1,3-disubstituted allyl alcohol esters by chiral aldehyde/palladium combining catalysis is systematically investigated.At first,we optimize the reaction conditions through the screening of catalysts,reaction solvents,bases,etc.Under the optimal conditions,we then examined the substrates scopes of amino acid esters and 1,3-disubstituted allyl alcohol esters.A series ofα,α-bisubstituted amino acid derivatives containing adjacent chiral centers have been constructed with moderate-to-excellent yields,diastereoselectivities and excellent enantioselectivities.In chapter 3,we studied the asymmetric allylation of amino acid esters with dienes promoted by chiral aldehydes/palladium catalysts.Through the optimization of reaction conditions and the expansion of substrate scopes,a series ofα,α-bisubstituted amino acid derivatives were obtained with a yield of up to 97%and enantioselectivity of up to 96%ee.The reaction mechanism was preliminarily investigated by control experiments,and a reasonable chiral control model is proposed.