Modular Chiral-Aldehyde/Palladium Catalysis Enables Atom-Economical α-Allylation of N-Unprotected Amino Acid Esters with 1,3-Dienes and Allenes
Jianhua Liu, Qing Zhou, Yao Lin, Zhu‐Lian Wu, Tian Cai, Wei Wen, Yanmin Huang, Qi‐Xiang Guo
Abstract
Herein, we report a chiral-aldehyde/palladium-catalyzed atom-economic asymmetric α-allylation of N-unprotected amino acid esters with unsaturated hydrocarbons. Chiral-aldehyde catalysis provides active nucleophilic intermediates from amino acid esters, while palladium catalysis provides the active electrophilic π-allyl metal species via hydrometallation of the unsaturated hydrocarbons. Accordingly, asymmetric α-allylation of N-unprotected amino acid esters with both 1,3-dienes and allenes can be achieved with high efficiency, allowing various α,α-disubstituted unnatural α-amino acid esters to be generated in good-to-excellent yields and stereoselectivities. No N-allylation byproducts are formed in these two reactions. Based on the results of mechanistic control experiments, two reaction models are proposed. Overall, this work demonstrates a completely atom-economical method for preparing structurally diverse chiral amino acids and provides guidance for developing further chiral-aldehyde catalytic systems.