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Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

ABSTRACT: 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.

SUBMITTER: Sakai HA

PROVIDER: S-EPMC7750884 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

Sakai Holt A HA Liu Wei W Le Chi Chip CC MacMillan David W C DWC

Journal of the American Chemical Society 20200626 27

Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp<sup>3</sup>)-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 cro ...[more]

PMID: 32564602

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