A S_N1 mechanistic approach to the Williamson ether reaction via photoredox catalysis applied to benzylic C(sp³)–H bonds

Dedication: This article is dedicated to Professor Stephen F. Martin, whose lab I got my start in when I was an undergraduate student. It was here I realized my love for organic chemistry, which I attribute to the caring environment Steve worked hard to establish amongst his group. This work: The Williamson ether reaction typically requires harsh conditions including strong base, elevated temperatures and long reaction times. The importance of ethers in valuable small molecules has thus motivated a search for mild alternatives. We report on a photochemical S_N1 reaction that employs C–H precursors in place of C–Br/Cl/OTs electrophiles. The key design in achieving the S_N1 approach relies on the direct generation of a carbocation from a given C–H bond via a photoredox-catalyzed formal hydride abstraction process. A wide substrate scope consisting of 1°, 2° and 3° alcohols was achieved, including examples of base-sensitive functionalities that are not compatible with Williamson ether conditions. Late-stage etherification of drug scaffolds is also demonstrated.