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 Lu; Bo Zhou; Long-Wu Ye

doi:10.1038/s41467-024-46288-7

Enantioselective functionalization of unactivated C(sp³)-H bonds through copper-catalyzed diyne cyclization by kinetic resolution

Nat Commun. 2024 Mar 12;15(1):2232. doi: 10.1038/s41467-024-46288-7.

Authors

Yang-Bo Chen¹, Li-Gao Liu¹, Zhe-Qi Wang¹, Rong Chang¹, Xin Lu², Bo Zhou¹, Long-Wu Ye^{3

4}

Affiliations

¹ State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
² State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. xinlu@xmu.edu.cn.
³ State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. longwuye@xmu.edu.cn.
⁴ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China. longwuye@xmu.edu.cn.

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.

Grants and funding

22125108, 22331004, 22121001 and 92056104/National Natural Science Foundation of China (National Science Foundation of China)