Highly enantioselective Rh-catalyzed asymmetric reductive dearomatization of multi-nitrogen polycyclic pyrazolo[1,5- a]pyrimidines

Chaochao Xie; Guiying Xiao; Qianling Guo; Xiaoxue Wu; Guofu Zi; Wanjian Ding; Guohua Hou

doi:10.1039/d3sc02086j

Highly enantioselective Rh-catalyzed asymmetric reductive dearomatization of multi-nitrogen polycyclic pyrazolo[1,5- a]pyrimidines

Chem Sci. 2023 Jul 28;14(34):9048-9054. doi: 10.1039/d3sc02086j. eCollection 2023 Aug 30.

Authors

Chaochao Xie¹, Guiying Xiao¹, Qianling Guo¹, Xiaoxue Wu¹, Guofu Zi¹, Wanjian Ding¹, Guohua Hou^{1

2}

Affiliations

¹ Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal University No. 19 Xinjiekouwai St. Beijing 100875 China ghhou@bnu.edu.cn dingwanjian@bnu.edu.cn.
² Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University Shanghai 200240 China.

Abstract

A highly enantioselective rhodium-catalyzed reductive dearomatization of 7-substituted pyrazolo[1,5-a]pyrimidines has been realized for the first time by two strategies to afford chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidines with excellent enantioselectivities of up to 98% ee. This method also provides an efficient approach for the synthesis of the powerful BTK inhibitor, zanubrutinib.