Core Structure-Oriented Asymmetric α-Allenylic Alkylation of Amino Acid Esters Enabled by Chiral Aldehyde/Palladium Catalysis

Org Lett. 2024 Jan 12;26(1):153-159. doi: 10.1021/acs.orglett.3c03762. Epub 2023 Dec 22.

Abstract

Aiming at the reported chiral synthons leading to manzacidins A and D, here we report a highly efficient catalytic asymmetric α-allenylic alkylation reaction of NH2-unprotected amino acid esters that is promoted by combined chiral aldehyde/palladium catalysis. Fifty examples of unnatural α,α-disubstituted amino acid esters are reported with good-to-excellent yields and stereoselectivities. Based on this methodology, a key intermediate leading to manzacidin C and its other three stereoisomers is prepared accordingly.