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.