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

Abstract

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.

Directing-Group-Assisted Non-Strained Ether C–O Bond Homolysis Mediated by Low-Valent Titanium

“…Because the tested benzyl ethers were prepared from benzyl bromides (and alcohols), this method seems roundabout in comparison with the previously reported alcohol CO bond cleavage . However, the presented method would be advantageous in that it is applicable to cyclic ethers.…”

“…Recently, we reported that the low-valent titanium (LVT) prepared from “TiCl 2 (cat)” (cat = catecholate) and Zn homolytically cleaved non-activated alcohol C–O bonds and C–Cl bonds (Figure B). , Owing to its unique reactivity, we envisaged that it could also activate non-strained ethers. Herein, we report the homolytic cleavage of non-strained ether C–O bonds and its application to representative radical addition reactions to alkenes (Figure C).…”

“…To investigate if it is possible to activate a relatively weak ether C–O bond, we first examined the reactivity of benzyl methyl ether ( 1 ) under our typical conditions originally developed for cleaving alcohol C–O bonds . An established radical addition reaction to alkenes was chosen for the purpose of detecting a carbon radical …”