From-Neutral-to-Neutral Reductive Radical Coupling of Non-Activated Alcohols and Styrenes

A reductive radical coupling reaction between non-activated aliphatic alcohols and styrenes has been discovered through the use of low-valent Ti-mediated C−O bond homolysis. A general application of styrene derivatives in radical coupling reactions remains a challenge in organic synthesis. The preliminary investigation revealed that the resulting benzyl radical intermediate behaves differently depending on minor steric differences around the spin center, which results in a lack of generality. The addition of 1,3,5-trimethyl-2,5-cyclohexadiene uniformly hydrogenated the benzyl radicals irrespective of the steric environments of the attacking radicals. Under the optimal reaction conditions, all tertiary, secondary, and primary alcohols were applicable. In this study, alcohols were successfully used directly as radical sources and reacted with a large number of styrenes.