Late-stage azolation of benzylic C‒H bonds enabled by electrooxidation

作     者：Zhixiong Ruan Zhixing Huang Zhongnan Xu Shaogao Zeng Pengju Feng Ping-Hua Sun Zhixiong Ruan;Zhixing Huang;Zhongnan Xu;Shaogao Zeng;Pengju Feng;Ping-Hua Sun

作者机构：Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences&the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of EducationCollege of PharmacyJinan UniversityGuangzhou 510632China Department of ChemistryJinan UniversityGuangzhou 510632China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2021年第64卷第5期

页      面：800-807页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 07[理学] 070303[理学-有机化学] 0703[理学-化学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(21901052,81872759) the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2019) the Guangzhou Education Bureau University Scientific Research Project(201831845) the Guangdong Basic and Applied Basic Research Foundation(2020A1515010722). 

主　　题：electrooxidation azolation external oxidant-free cross-dehydrogenative coupling late-stage functionalization 

摘      要：The installation of azoles via C–H/N–H cross-coupling is significantly underdeveloped,particularly in benzylic C–H azolation due to the requirement for external chemical oxidants and the challenge in controlling the site-and chemo-selectivity.Herein,a late-stage azolation of benzylic C‒H bonds enabled by electrooxidation is described,which proceeds in an undivided cell under mild,catalyst-and chemical-oxidant-free reaction conditions.The strategy empowers the C‒H azolation on primary,secondary,and even challenging tertiary benzylic positions selectively.The remarkable synthetic utility of our approach is highlighted by its easy scalability without overoxidation of products and ample scope with valuable functional groups.The approach can be directly used to install benzyl and azole motifs on highly functionalized drug molecules.