Enantioselective functionalization of unactivated C(sp3)–H bonds through copper-catalyzed diyne cyclization by kinetic resolution
Yang‐Bo Chen, Li‐Gao Liu, Zhe-Qi Wang, Rong Chang, Xin Lü, Bo Zhou, Long‐Wu Ye
Abstract
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(sp 3 )–H functionalization reactions, the catalytic enantioselective C(sp 3 )–H functionalization based on vinyl cations, especially for an unactivated C(sp 3 )–H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp 3 )–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(sp 3 )–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(sp 3 )–H insertion reaction and elucidate the origin of enantioselectivity.