SET Cleavage of Peroxides: Influence of Reductant and Peroxide on the Reactivity and Regioselectivity of Alkoxy Radical Formation

Alkoxy radicals are an important class of reactive intermediates frequently generated through single electron transfer (SET) reductions of organic peroxides. We investigated the reactions of a family of peroxide probes with a series of metal and photoredox reductants, with a focus on reactivity as well as regioselectivity of cleavage in terms of selectivity of alkoxy radical generation. A hydroperoxide and perester were reactive toward all reductants and cleaved with high, and in some cases, complete selectivity for generation of the alkoxy radical. A peroxyacetal was less reactive and the dependence of cleavage mode on reductant suggests competition between steric and stereoelectronic influences. A trialkylsilyl peroxide was much less reactive and, consistent with previous reports, demonstrated high selectivity for generation of the alkoxy radical vs silyloxy radical. Dialkyl peroxides displayed variation in both reactivity and selectivity depending upon steric hindrance and the nature of the reducing system. We found that the [Ru(bpy)₃]^2+/3+ system, although unreactive toward dialkyl peroxides under photoredox conditions, was capable of cleaving even an extremely hindered substrate when electrochemically driven to a state or states of suitable reducing potential. Overall, results suggest unanticipated complexity in the reduction of several classes of peroxides and point to new opportunities for selective generation of desired alkoxy radicals.