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
Affiliations
Tian-Jiao Han
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China
Chun-Yan Guan
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China
Na Li
School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255000, Shandong, China
Rui Dong
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China
Li-Ping Xu
School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255000, Shandong, China
Xiao Xiao
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, People’s Republic China
Min-Can Wang
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China; Corresponding author
Guang-Jian Mei
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China; Corresponding author
Summary: 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.
