Polarizability matters in enantio-selection

Fumin Chen; Yu Chen; Xiao-Yong Chang; Dongxu He; Qingjing Yang; David Zhigang Wang; Chen Xu; Peiyuan Yu; Xiangyou Xing

doi:10.1038/s41467-024-47813-4

Polarizability matters in enantio-selection

Nat Commun. 2024 Apr 22;15(1):3394. doi: 10.1038/s41467-024-47813-4.

Authors

Fumin Chen^#^{1

2}, Yu Chen^#², Xiao-Yong Chang², Dongxu He², Qingjing Yang², David Zhigang Wang³, Chen Xu⁴, Peiyuan Yu⁵, Xiangyou Xing⁶

Affiliations

¹ School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.
² Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055, China.
³ Shenzhen Youwei Tech Group, Shenzhen, 518057, China.
⁴ Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055, China. xuc@sustech.edu.cn.
⁵ Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055, China. yupy@sustech.edu.cn.
⁶ Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055, China. xingxy@sustech.edu.cn.

^# Contributed equally.

Abstract

The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates' local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.