Decatungstate-Catalyzed C(sp<sup>3</sup>)–H Alkylation of a Val Residue Proximal to the N-Terminus Controlled by an Electrostatic Interaction
Jizhou Song, Takeru Torigoe, Yoichiro Kuninobu
Abstract
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.