Visible-light-induced photochemical approaches to n-heterocycle functionalization and bioconjugation

Abstract

The light obtained from sustainable resources is an ideal reagent for chemical synthesis from the perspective of “green” chemistry. While high-energy ultraviolet rays (UV) have been employed for initiating certain photochemical processes, this traditional approach is typically plagued by concurrent side reactions that limit their practicality in synthesis. Visible-light sensitization is an important emerging way to access reactive radical intermediates under much milder conditions and reveals a new opportunity for synthetic transformations via the controllable one-electron mechanism. This dissertation describes research centered on photochemical approaches induced by visible light. Specifically, within this unified theme, the selective peripheral modifications of N-heterocycles and biomolecules, both of which are the main frameworks of preclinical candidates and marketed drugs, have been explored. The results have been disseminated in three separated achievements: (i) Sulfonative pyridylation of alkenes enabled by electron donor-acceptor (EDA) complexes and an ionic sulfonylation at the C4 positions of pyridine, (ii) photocatalytic generation of fluoroalkyl and sulfonyl radicals via cascades and introduction reactions to pyridylic positions, and (iii) cysteine-specific bioconjugation installing fluorophore and biologically-relevant groups via thiol-ene click reactions.