Iron-mediated Remote C-H Bond Benzylation Of 8-Aminoquinoline Amides

Quinolines represent an important class of N-based heterocyclic compounds due to their wide spectrum of anti-malarial,antibacterial,antifungal agent and anticancer activities.They can also be used as directing groups or ligands in organic reactions.Thus,the development of efficient methods for synthesizing substituted amidoquinoline derivatives has attracted tremendous researches interest in organic synthesis.A highly desirable synthetic method is the site-selective C-H functionalization of a preformed quinoline scaffold.But due to the electron nature of quinoline moieties,it is usually not easy to control the regio-selectivity.Several successful transformations are mainly focusing on the functionalization at the C2 position owing to the intrinsic reactivity of the C=N bonds.Regio-selective functionalization at C3 and C8 positions of quinolines had also been disclosed.However,much less effort had been taken to the functionalization at the C5 position of quinoline derivatives with high regio-selectivity.As a continuation of our previous work,in the submitted paper we now report the first example iron-catalyzed remote C5 C-H benzylation of quinolines.The reaction condition is mild and have excellent regio-selectivity.This newly developed reaction shows good functional-group compatibility.N-benzylic sulfonamides smoothly reacted with aliphatic amides and aromatic amides gave rise to the corresponding products in moderate to excellent yields.It affords an easy access to the synthesis of various functionalized amidoquinoline derivatives.