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

Abstract

Summary: 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 Csp3–Csp3 bonds remain underdeveloped. Here we describe the direct, photoredox cleavage of hindered Csp3–Csp3 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 (Eox½ > +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.

Keywords

• photoredox catalysis
• proton-coupled electron transfer
• C–C cleavage of alcohols
• alkyl radical species
• various radicalophiles