Cu-catalyzed Asymmetric Alkylation for Chiral Unnatural α-Substituted α-Amino Acids of Phallotoxins

Asymmetric alkylation is one of the most important methods for synthesizing chiral unnatural α-substituted α-amino acids. Herein, We reported an asymmetric alkylation of tert-butyl glycinate Schiff base catalyzed by copper/(4S,2R)-tBu-Phosferrox catalysts. This catalyst shows high catalytic performance in the asymmetric alkylation at 1 mol % catalyst loading, giving the products with up to 95% yield and >99% ee. This method was successfully applied to synthesize a series of phallotoxins chiral unnatural α-substituted α-amino acids and the key intermediate, such as α-AAs-7 (4,5-OH-Leu) derivatives.