Formal C─H Functionalization of Quinolines at the C7 Position Through a Traceless Directing Strategy

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.