Decatungstate-Catalyzed C(sp 3 )-H Alkylation of a Val Residue Proximal to the N-Terminus Controlled by an Electrostatic Interaction.

The decatungstate photocatalyst [W 10 O 32 ] 4- efficiently promoted the C(sp 3 )-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 ( + NH 3 ) of the main chain and anionic [W 10 O 32 ] 4- played an important role in this reaction. The influence of various protected amino acids in the C(sp 3 )-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(sp 3 )-H bond of a Val residue located at the second from the N-terminus was also successfully converted. C(sp 3 )-H alkylation of oligopeptides containing two Val residues selectively proceeded proximally to the N-terminus.