C3-H Amination of Quinolines Enabled by a Tailored Aminating Agent

High Resolution Image Download MS PowerPoint Slide 3-Aminoquinolines are privileged heterocyclic motifs widely used in medicinal chemistry and functional materials. However, their efficient and regioselective synthesis remains highly challenging due to the intrinsic electronic bias of the quinoline ring and compatibility issues of the reaction system. Direct C3-H amination of quinolines represents one of the most straightforward and efficient strategies, yet practical and effective methods for this transformation remain rare. Against these challenges, we report a thermodynamically driven direct meta -C-H amination of quinolines. With quinoline N -oxides as substrates and benzyl N -(1-chloro-2,2,2-trifluoroethylidene)carbamate (BzCTC) as the amino source, the reaction proceeds via 1,2-addition, dearomative [3,3]-sigmatropic rearrangement, and rearomatization, followed by a one-pot hydrolysis. This approach enables the first direct installation of a free amino group at the meta -position of quinolines. The use of BzCTC as a novel amination reagent is crucial; it not only enhances reaction reactivity but also guarantees chemoselectivity. The practicality of this method is demonstrated by the synthesis and late-stage modification of bioactive molecules.