Carbon-heteroatom bond formation via photochemical application of quinolinones and enantioselective functionalization of pyridines

Abstract

Visible-light-induced radical cyclization of quinolinone-containing substrates has been developted utilizing the photochemical activity of quinolinone scaffold without external photocatalyst. Nitrogen-oxygen bond dissociation induced by single-electron transfer (SET) between excited quinolinone substrate and pyridinium salt led to the formation of phosphine-centered radical. Generated phosphine-centered radical inserted into alkene appendage of quinolinone substrates, and the following tandem reaction allows the efficient formation of carbon-phosphine bond and new synthetic pathway for tetrahydrophenanthridin-6(5H)-ones. Furthermore, exploting the intrinsic photosensitizing ability of modified quinolinone scaffold, I developed water-compatible fluorescent photosensitizer, which can be used for visible-light-induced cycsteine-specific bioconjugation for the installation of fluorophore. The slightly modified quinolinone photocatalyst enabled the effective photocatalytic cysteine-specific conjugation of biologically relevant groups. The superior reactivity and cysteine selectivity were further corroborated by efficient bioconjugation with a series of complex peptides and proteins under biocompatible coditions to generate stable carbon-sulfur conjugate bond. An efficient method for the C4-selective asymmetric alkylation of pyridines has been reported via N-heterocyclic carbene (NHC) catalysis with excellent control over enantioselectivity and pyridyl C4-selectivity. The key strategy for precise stereocontrol involves enhancing interaction between the chiral NHC-bound homoenolate and pyridinium salt in the precence of hexafluorobenzene, which effectively differenciates the two faces of the homoenolate radical. The reaction efficiency is further accelerated by visible light irradiation. This methodology enables facile access to a diverse range of enantioenriched C4-alkylated pyridines under mild and metal-free conditions.