Cross-Electrophile Coupling of Unactivated Alkyl Chlorides

Alkyl
chlorides are bench-stable chemical feedstocks that remain
among the most underutilized electrophile classes in transition metal
catalysis. Overcoming intrinsic limitations of C­(sp3)–Cl
bond activation, we report the development of a novel organosilane
reagent that can participate in chlorine atom abstraction under mild
photocatalytic conditions. In particular, we describe the application
of this mechanism to a dual nickel/photoredox catalytic protocol that
enables the first cross-electrophile coupling of unactivated alkyl
chlorides and aryl chlorides. Employing these low-toxicity, abundant,
and commercially available organochloride building blocks, this methodology
allows access to a broad array of highly functionalized C­(sp2)–C­(sp3) coupled adducts, including numerous drug
analogues.