Benzotriazolyl Radical-Mediated C(sp3)-H Functionalization under Visible-Light Irradiation

Abstract

Benzotriazolyl (Bt) radicals, generated via visible-light-induced N–O bond photolysis of N-enoxybenzotriazoles, serve as effective hydrogen atom transfer (HAT) mediators for selective α-C(sp3)–H functionalization of ethers. The exceptionally high N–H bond dissociation energy of benzotriazole (108 kcal/mol) allows Bt radicals to abstract strong C–H bonds, while their photochemical generation from readily prepared N-enoxybenzotriazoles circumvents the prohibitively high oxidation potential of benzotriazole itself (E°ox = 2.20 V vs SCE). Bt radicals selectively abstract α-hydrogens from a broad range of (thio)ethers and (thio)acetals bearing secondary and tertiary C–H bonds, as well as benzylic C–H bonds in p-cresol derivatives. The resulting α-alkoxy radicals add to N-enoxybenzotriazoles to deliver β-alkoxy ketones as an aldol surrogate through an exceptionally efficient radical chain propagation (Φ = 291). The protocol further extends to a three-component radical addition, in which α-alkoxy radicals are intercepted by electron-deficient olefins to afford coupled products with high chemoselectivity.