Catalytic atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes via dynamic kinetic resolution

Tian-Jiao Han; Chun-Yan Guan; Na Li; Rui Dong; Li-Ping Xu; Xiao Xiao; Min-Can Wang; Guang-Jian Mei

doi:10.1016/j.isci.2023.107978

Catalytic atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes via dynamic kinetic resolution

iScience. 2023 Sep 20;26(10):107978. doi: 10.1016/j.isci.2023.107978. eCollection 2023 Oct 20.

Authors

Tian-Jiao Han¹, Chun-Yan Guan¹, Na Li², Rui Dong¹, Li-Ping Xu², Xiao Xiao³, Min-Can Wang¹, Guang-Jian Mei¹

Affiliations

¹ College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
² School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255000, Shandong, China.
³ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, People's Republic China.

Abstract

Reported herein is a highly efficient dynamic kinetic resolution protocol for the atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes. Atropisomers bearing vicinal diaxes mainly exist in o-triaryls, while that of biaryls is highly challenging in terms of the concerted rotation and deplanarization effects. The combination of C-C biaryl with N-N nonbiaryl delivers a novel class of vicinal-diaxis heterobiaryls. For their atroposelective synthesis, the dynamic kinetic resolution enabled by either quinine-catalyzed allylation or isothiourea-catalyzed acylation has been developed, allowing the preparation of a wide range of vicinal-axis heterobiaryls in good yields with excellent enantioselectivities. Atropisomerization experiments revealed that the C-C bond rotation led to diastereomers, and the N-N bond rotation offered enantiomers. Besides, this protocol could be extended to kinetic resolution by employing substrates with a more hindered axis.

Keywords: Catalysis; Chemical reaction engineering; Chemistry; Organic chemistry.