Catalytic cleavage and functionalization of bulky and inert Csp3–Csp3 bonds via a relayed proton-coupled electron transfer strategy

Abstract

Catalytic cleavage and functionalization of unstrained carbon–carbon bonds represent a formidable challenge for synthetic chemistry. Despite tremendous advances in transition-metal catalysis and photoredox radical chemistry, methods for the cleavage of sterically crowded inert C sp3 –C sp3 bonds remain underdeveloped. Here we describe the direct, photoredox cleavage of hindered C sp3 –C sp3 bonds of alcohols under neutral conditions. A relayed proton-coupled electron transfer (PCET) strategy is employed that overcame the previous requirement of a Brønsted base. Heavily branched alcohols with a high oxidation potential ( E ox½ > +2 V versus saturated calomel electrode) are cleaved and functionalized with remarkable efficiency and versatility. A simple, non-substituted phenyl group can promote a relayed PCET process to deliver primary, secondary, and tertiary alkyl radicals under neutral conditions. • Proton-coupled electron transfer • C–C cleavage of alcohols • Alkyl radicals • Various radicalophiles Liao et al. report a Fukuzumi acridinium salt as a catalyst for the C–C bond cleavage of linear primary, secondary, and tertiary carbinols under neutral conditions. The resulting transient alkyl radical species can be intercepted using various radicalophiles, including electron-deficient alkenes, an electrophilic SCF 3 reagent, and a range of heteroaryls.