Catalysis

Engineering

Electrophile

Coupling (piping)

Transition metal

Alkyl

Mechanical engineering

Medicinal chemistry

Combinatorial chemistry

Organic chemistry

Reagent

Computational chemistry

Chemistry

Aryl

Adduct

Journal of the American Chemical Society

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.

Cross-Electrophile Coupling of Unactivated Alkyl Chlorides