Research On Regioselective C-H Halogenation Of 8-aminoquinoline Derivatives

Quinolines and quinoline derivatives are important building blocks in organic synthesis.At the same time,halogenated on their phenyl counterparts are indispensable to the synthesis of biological and pharmaceutical compounds as well as advanced functional materials.Traditionally,heteroaromatic halogens are formed via electrophilic substitution by the halogens or other halogenated reagents,suffering from known limitations including complex procedure,poor chemoselectivity and environmental concerns.Recently,the direct functionalization of C-H bonds via transition metal catalyzed has been developed as researsh spot and challenge in organic chemistry for it not only can greatly improve the atom economy,but also accord with the idea of green chemistry.8-Aminoquinoline served as excellent and powerful N,N-bidentate directing groups,contributing much to the direct sp 2 and sp3 C-H activation via metal chelation strategy.In our labortary,we are continuously focused on the research of regioselective of functionalization of 8-aminoquinoline and got good progress in the selective halogenation.In this paper,we described a highly selective protocol for halogenating of N-(8-quinolinyl)amides on the C-5 position.The experimental part of this paper includes two aspects of content.The first one,we have demonstrated the effective halogenation of N-(8-quinolinyl)amides on C-5 position under mild conditions.Without any additives,the remote regioselective access to quinolines was achieved when cuprous halides served as halides source combined with NFSI as oxidant.Different chloro-,bromo-and iodo-C-5 substituted N-(8-quinolinyl)amides were all prepared in good yields,indicating the excellent functional tolerance in this protocol.In comparison with other reported methods,our protocol provided a simple but highly selective route in synthesizing diverse halogenated compounds.The second one,we first developed Nickel-catalyzed C-H fluorination of N-(8-quinolinyl)amides in the C-5 position.The protocol using NFSI(N-Fluorobenzenesulfonimide)as the “F” reagent,Ni SO4 as the catalyst and DCE as solvent,produced remote C-H fluorination with broad substrate scope.To gain insight into the reaction mechanism,control experiment was performed and this result suggested that free radical was involved in the reaction process.The plausible mechanism underwent radical process was provided herein.Last but not least,we choose 8-aminoquinoline served as directing group to direct sp3 C-H cyanation.After a serious of research,unfortunately,we didn’t get ideal experimental results.But these results will provide a good idea and basis for the future exploration.