In conclusion, we demonstrated highly efficient chiral aldehyde-catalyzed substitution reactions of N-amino acid esters with aryl, allyl, and benzyl In the promotion of the simple chiral aldehyde CA-1, the arylation reaction of N-unprotected amino acid esters with aryl halides takes place smoothly, giving aryl disubstituted amino acid moderate-to-high yields with good-to-excellent enantioselectivities. combinational catalytic system comprising chiral aldehyde CA-15 and Lewis acid ZnCl2 efficiently promotes the reactions of allylation and benzylation, giving allyl and benzyl disubstituted amino acid derivatives in moderate-to-good yields with good-to-excellent enantioselectivities. The arylation product 3o is used for the formal total synthesis of AG-041R, and three transition states are proposed to illustrate the stereoselective-control results.