Rhodium-catalyzed enantioselective and diastereodivergent access to diaxially chiral heterocycles

Yishou Wang; Xiaohan Zhu; Deng Pan; Jierui Jing; Fen Wang; Ruijie Mi; Genping Huang; Xingwei Li

doi:10.1038/s41467-023-39968-3

Rhodium-catalyzed enantioselective and diastereodivergent access to diaxially chiral heterocycles

Nat Commun. 2023 Aug 3;14(1):4661. doi: 10.1038/s41467-023-39968-3.

Authors

Yishou Wang¹, Xiaohan Zhu², Deng Pan³, Jierui Jing², Fen Wang⁴, Ruijie Mi¹, Genping Huang⁵, Xingwei Li^{6

7}

Affiliations

¹ Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Sciences, Shandong University, 266237, Qingdao, China.
² School of Chemistry and Chemical Engineering, Shaanxi Normal University, 710062, Xi'an, China.
³ Department of Chemistry, School of Science and Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin University, 300072, Tianjin, China.
⁴ School of Chemistry and Chemical Engineering, Shaanxi Normal University, 710062, Xi'an, China. fenwang@snnu.edu.cn.
⁵ Department of Chemistry, School of Science and Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin University, 300072, Tianjin, China. gphuang@tju.edu.cn.
⁶ Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Sciences, Shandong University, 266237, Qingdao, China. lixw@snnu.edu.cn.
⁷ School of Chemistry and Chemical Engineering, Shaanxi Normal University, 710062, Xi'an, China. lixw@snnu.edu.cn.

Abstract

N-N axially chiral biaryls represent a rarely explored class of atropisomers. Reported herein is construction of diverse classes of diaxially chiral biaryls containing N-N and C-N/C-C diaxes in distal positions in excellent enantioselectivity and diastereoselectivity. The N-N chiral axis in the products provides a handle toward solvent-driven diastereodivergence, as has been realized in the coupling of a large scope of benzamides and sterically hindered alkynes, affording diaxes in complementary diastereoselectivity. The diastereodivergence has been elucidated by computational studies which revealed that the hexafluoroisopropanol (HFIP) solvent molecule participated in an unusual manner as a solvent as well as a ligand and switched the sequence of two competing elementary steps, resulting in switch of the stereoselectivity of the alkyne insertion and inversion of the configuration of the C-C axis. Further cleavage of the N-directing group in the diaxial chiral products transforms the diastereodivergence to enantiodivergence.