Palladium-catalyzed remote internal C(sp<sup>3</sup>)-H bond chlorination of alkenes.

Wang, Yao-Xin; Wang, Zhen; Yang, Xiao-Hui · Nat Commun · 2024

basic_science · Level V

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Abstract

C(sp<sup>3</sup>)-Cl bonds are present in numerous biologically active molecules and can also be used as a site for diversification by substitution or cross-coupling reactions. Herein, we report a remote internal site-selective C(sp<sup>3</sup>)-H bond chlorination of alkenes through sequential alkene isomerization and hydrochlorination, enabling the synthesis of both benzylic and tertiary chlorides with excellent site-selectivity. This transformation offers exciting possibilities for the late-stage chlorination of derivatives of natural products and pharmaceuticals. We also demonstrate the regioconvergent synthesis of a single alkyl chloride from unrefined mixtures of isomeric alkenes, which can be extracted directly from petrochemical sources.