Nickel-catalysed stereoselective α-vinylation and arylation of peptide electrophiles

Stereoselective modification peptide α-carbons remains a challenge. In this context, transition metal-catalyzed C-C cross-coupling chemistry of peptidyl α-carbon-electrophiles has not been achieved. Herein, we report that racemic glycinyl α-C-Ts (α-TG) unit implanted in peptide backbones serves as an excellent electrophile element for vinylation/arylation with vinyl/aryl triflates/halides to afford the α-C(sp2)-modified peptides in excellent levels of diastereoselectivity, enabled by asymmetric Ni-catalyzed reductive coupling platform. The stereocontrol is essentially governed by the catalyst, on which the α-substituents of the neighboring amino acid elements showed minor effect. The scope of peptides was broad, comprising decapeptides and cyclic pentapeptides. A unique feature of the present work is the viability of modification of the internal sites of the peptides, which stands a sharp contrast to the contemporary studies that focus on the N- or C-terminal peptide α-carbons. This work may provoke a broader interest in peptide backbone modification based on cross-coupling chemistry.