Site-Selective Cu-Catalyzed Alkylation of α-Amino Acids and Peptides toward the Assembly of Quaternary Centers

Abstract

The Cu^I -catalyzed selective α-alkylation of α-amino acid and peptide derivatives with 2-alkyl-1,3-dioxolanes is reported. This oxidative coupling is distinguished by its site-specificity, high diastereoselectivity, and chirality preservation and exhibits absolute chemoselectivity for N-aryl glycine motifs over other amino acid units. Collectively, the method allows for the assembly of challenging quaternary centers, as well as compounds derived from natural products of high structural complexity, which may provide ample opportunities for late-stage functionalization of peptides.

Keywords: C−H functionalization; alkylation; copper; homogeneous catalysis; peptides.