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

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 Bronsted base. Heavily branched alcohols with a high oxidation potential (E-ox1/2 > +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.

Automated summary

This study achieved the photoredox cleavage of hindered C-sp3-C-sp3 bonds under neutral conditions by employing a relayed proton coupled electron transfer strategy, enabling the cleavage and functionalization of highly branched alcohols.