Decatungstate-Catalyzed C(sp³)–H Alkylation of a Val Residue Proximal to the N‑Terminus Controlled by an Electrostatic Interaction

Abstract

The decatungstate photocatalyst [W10O32]4– efficiently promoted the C­(sp3)–H alkylation of the trifluoroacetic acid salt of valine methyl ester (H-Val-OMe·TFA) with electron-deficient alkenes under UV irradiation. The electrostatic interaction between the cationic ammonium group (+NH3) of the main chain and anionic [W10O32]4– played an important role in this reaction. The influence of various protected amino acids in the C­(sp3)–H alkylation was investigated as the model reaction for the alkylation of Val-containing peptides. The introduction of an alkyne moiety into Val through this alkylation was successful, and successive copper-catalyzed azide–alkyne cycloaddition (CuAAC) was demonstrated. The C­(sp3)–H bond of a Val residue located at the second from the N-terminus was also successfully converted. C­(sp3)–H alkylation of oligopeptides containing two Val residues selectively proceeded proximally to the N-terminus