Alkoxy Radical Generation Mediated by Sulfoxide Cation Radicals for Alcohol-Directed Aliphatic C–H Functionalization

The C–H functionalization of remote, unactivated C–H bonds offers a unique method of garnering structural complexity in a synthesis. The use of directing groups has provided a means of enacting C–H functionalization on these difficult-to-access bonds; however, the installation and removal of directing groups on a substrate require additional synthetic manipulations, detracting from both the efficiency and economic feasibility of a transformation. The use of alkoxy radicals as transient directing groups for the functionalization of remote C–H bonds allows access to the synthesis of complex molecules without the need for additional functionality. Herein, we report a method for alkoxy radical formation from unactivated alcohols and reactivity mediated by photoredox-generated sulfoxide cation radicals. This protocol leverages the unique reactivity of alkoxy radicals to implement different reaction manifolds: 1,5-hydrogen atom transfer (HAT), cyclization, and β-scission. Furthermore, it was discovered that this methodology could be utilized to impose radical group transfer reactions via the β-scission pathway. Stern–Volmer analysis supports the formation of an alkoxy radical via the intermediacy of a sulfurane radical rather than a proton-coupled electron transfer (PCET) mechanism.