Enantioselective functionalization of unactivated C(sp<sup>3</sup>)-H bonds through copper-catalyzed diyne cyclization by kinetic resolution.

Chen, Yang-Bo; Liu, Li-Gao; Wang, Zhe-Qi; Chang, Rong; Lu, Xin; Zhou, Bo; Ye, Long-Wu · Nat Commun · 2024

basic_science · Level V

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Abstract

Site- and stereoselective C-H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)-H functionalization reactions, the catalytic enantioselective C(sp3)-H functionalization based on vinyl cations, especially for an unactivated C(sp3)-H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)-H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)-H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)-H insertion reaction and elucidate the origin of enantioselectivity.