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.

Development and application of decatungstate catalyzed C–H 18F- and 19F-fluorination, fluoroalkylation and beyond

“…In further explorations of site-selective C(sp 3 )–H functionalization, Torigoe, Kuninobu and co-workers have reported a decatungstate C(sp 3 )–H alkylation of valine derivatives 60 with electron-deficient alkenes. 100 Here, the initially alkylated product 61 undergoes hydrolysis and cyclization to afford δ-lactam 62 (Scheme 15a). Notably, and similar to our findings with leucine, 89 the valine derivatives, H–Val–OMe ( 63 ), Ac–Val–OMe ( 64 ) and methyl isovalerate ( 65 ) did not react under the same conditions, highlighting the importance of electrostatic interactions in accelerating the HAT step (Scheme 15b).…”

Non‐Covalent Interaction‐Controlled Site‐Selective C−H Transformations

“…The site-selective C(sp 3 )À H alkylation of tripeptides with two Val residues proceeded at the Val residue closer to the ammonium group at the N-terminus of the tripeptides Val-Ala-Val and Ala-Val-Val (Schemes 18 and 19). [23] Scheme 17. Site-selective C(sp 3 )À H alkylation of Aniline Derivatives.…”

Methionine-enabled peptide modification through late-stage Pd-catalyzed β-C(sp3)–H olefination/cyclization

“…6–8 Among these, late-stage transition metal-catalyzed C–H functionalization has emerged as a highly efficient strategy for postassembly modification of peptides. 9–11 In recent years, remarkable achievements have been made in the site-selective functionalization of peptides through metal-catalyzed C(sp 3 )–H activation enabled by exogenous auxiliaries, as exemplified by the pioneering contributions from Ackermann, 12 Shi, 13 Chen 14 Carretero 15 and other researchers. 16 In contrast, the development of C(sp 3 )–H functionalization on inert aliphatic residues of peptides mediated by endogenous groups remains considerably less explored.…”