Formal C─H Functionalization of Quinolines at the C7 Position Through a Traceless Directing Strategy
Abstract
Abstract The precise C─H functionalization of quinolines is of high interest in organic synthesis and drug discovery. However, although many strategies have been developed for the regioselective C─H bond functionalization of the quinoline scaffold, the facile and selective remote C─H bond functionalization of quinolines at the geometrically and electronically disfavored C7‐position has remained underdeveloped. Here, we disclose a Cu‐catalyzed formal C─H arylation and alkenylation of quinolines at the C7 position with diverse iodonium triflates. The reaction features exclusive C7‐selectivity, broad substrate scope, short reaction time, and simple operation. This practical protocol has also been applied in the analogous C7‐H functionalization of tetrahydroquinolines and the further C7‐elaboration of quinolines. Experimental studies and density functional theory (DFT) calculations revealed that the key to the success of this transformation is the unique ring‐size‐induced in situ removal of the N ‐acyl directing group, constituting a traceless directing strategy for the rapid access to a variety of C7‐substituted neutral quinolines.
Article Details
Authors (9)
Kun Zhou
Key Laboratory of Animal Virology, Ministry of Agricultural and Rural Affairs of China and Zhejiang Provincial Engineering Research Center of Animal Biological Products, Department of Veterinary Medicine, Zhejiang University College of Animal Sciences
Ni Zhang
Xin‐Rou Zhong
Catalytic Hydrogenation Research Center State Key Laboratory of Green Chemical Synthesis and Conversion Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province Zhejiang University of Technology Hangzhou 310014 P.R. China
Rui‐Rui Wu
Catalytic Hydrogenation Research Center State Key Laboratory of Green Chemical Synthesis and Conversion Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province Zhejiang University of Technology Hangzhou 310014 P.R. China
Yang‐Jie Mao
Catalytic Hydrogenation Research Center State Key Laboratory of Green Chemical Synthesis and Conversion Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province Zhejiang University of Technology Hangzhou 310014 P.R. China
Peng Ye
Catalytic Hydrogenation Research Center, State Key Laboratory of Green Chemical Synthesis and Conversion, Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province
Gen Luo
Institutes of Physical Science and Information Technology
Dan‐Qian Xu
Catalytic Hydrogenation Research Center State Key Laboratory of Green Chemical Synthesis and Conversion Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province Zhejiang University of Technology Hangzhou 310014 P.R. China
Shao‐Jie Lou
Catalytic Hydrogenation Research Center State Key Laboratory of Green Chemical Synthesis and Conversion Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province Zhejiang University of Technology Hangzhou 310014 P.R. China