Radical conjugate addition to 2-substituted chromones via an electron donor–acceptor complex

Abstract

A novel photocatalyst-free radical conjugate addition to 2-substituted chromones has been developed, utilizing Hantzsch esters and TMSOTf to efficiently access diverse 2,2-disubstituted chroman-4-ones under mild conditions. Mechanistic studies, including UV–vis spectroscopy and 1H NMR titration, indicate that the reaction proceeds via an electron donor–acceptor (EDA) complex, which is formed in situ through the reaction of TMSOTf with chromones to generate 4-siloxy-1-benzopyrylium salts. This versatile method enables late-stage functionalization of natural chromones, affording structurally diverse scaffolds with promising biological activity. The resulting chroman-4-one derivatives suppress cGAMP-induced immune responses in ISRE assays, whereas their parent chromones enhance these responses. These results highlight chroman-4-ones as promising immunosuppressive scaffolds for therapeutic development.