Catalytic asymmetric Tsuji–Trost benzylation is a promising strategy for the preparation of chiral benzylic compounds. However, only a few such transformations with both good yields and enantioselectivities have been achieved since this reaction was first reported in 1992, and its use in current organic synthesis is restricted. In this work, we use N-unprotected amino acid esters as nucleophiles in reactions with benzyl alcohol derivatives. A ternary catalyst comprising a chiral aldehyde, a palladium species, and a Lewis acid is used to promote the reaction. Both mono- and polycyclic benzyl alcohols are excellent benzylation reagents. Various unnatural optically active α-benzyl amino acids are produced in good-to-excellent yields and with good-to-excellent enantioselectivities. This catalytic asymmetric method is used for the formal synthesis of two somatostatin mimetics and the proposed structure of natural product hypoestestatin 1. A mechanism that plausibly explains the stereoselective control is proposed.

A ternary catalytic system comprising a chiral aldehyde, a transition metal, and a Lewis acid is rationally designed for the asymmetric α-allylic alkylation reaction of aza-aryl methylamines and π-allylmetal electrophiles. Structural diversity chiral amines bearing carbon–carbon double bonds and aza-heterocycles are produced in moderate to good yields with good to excellent enantioselectivities. These products can be readily converted into other chiral amines without the loss of enantioselectivity. A reasonable reaction mechanism is proposed to illustrate the stereoselective control results.

The first catalytic asymmetric cascade Heck-alkylation reaction of NH 2 -unprotected amino acid esters with N-(2iodophenyl)allenamides is reported in this work. Under the promotion of a combining catalytic system comprising a chiral aldehyde, a chiral palladium complex, and the Lewis acid ZnCl 2 , the title reaction takes place smoothly, giving optically active α-alkyl tryptophan derivatives in moderate to good yields and excellent enantioselectivities. The target products can be converted into other structurally complex chiral indoles without the loss of enantioselectivities.