Asymmetric α-Allylation of Amino Acid Esters with Alkynes Enabled by Chiral Aldehyde/Palladium Combined Catalysis

Org Lett. 2024 Sep 20;26(37):7908-7913. doi: 10.1021/acs.orglett.4c02840. Epub 2024 Sep 10.

Abstract

A highly efficient, atom-economical α-allylation reaction of NH2-unprotected amino acid esters and alkynes is achieved by chiral aldehyde/palladium combined catalysis. A diverse range of α,α-disubstituted nonproteinogenic α-amino acid esters are produced in 31-92% yields and 84-97% ee values. The allylation products are utilized for the synthesis of drug molecule BMS561392 and other chiral molecules possessing complex structures. Mechanistic investigations reveal that this reaction proceeds via a chiral aldehyde-/palladium-mediated triple cascade catalytic cycle.