Synthesis Of Isoquinolines Via Cobalt-catalyzed C-H Activation/Cyclization Assisted By Monodentate Directing Group

Isoquinoline is one of the most common nitrogen-containing heterocyclic compounds.They are widely distributed in the core framework of natural products,pharmaceuticals,organic light-emitting materials,and ligands for metal catalysts.Therefore,developing some efficient and direct synthetic methods of isoquinolines are highly desirable,which has also become an urgent problem for organic chemists to solve.Although traditional methods that mainly rely on the transition metal-catalyzed cross-coupling reaction can provide promising access to isoquinolines,they generally tend to suffer from problems such as producing large amount of toxic waste,requiring prefunctionalized substrates as well as harsh reaction conditions.In recent years,cheap metal-catalyzed monodentate ligand-directed C-H activation has become a popular research direction with its green,efficient,straightforward,and low-cost characteristics,and has been widely used in the research of functionalization of various compounds.Here,this article mainly discusses the synthesis of isoquinoline by tandem cyclization with C-H activation using cobalt salt as catalyst,imine as guiding group,benzimidyl ester and sulfoxide ylide as substrates.The main contents are as follows:(1)Cobalt-participating monodentate ligand-directed C-H activation reactions and the synthesis methods of isoquinoline derivatives and the project background?significance and research plan were introduced,respectively.(2)A series of experiments on cobalt-catalyzed C-H bond acylmethylation cyclization of benzimidates with sulfoxonium ylides has been carried out to explore the effects of the type and amount of cobalt catalysts,silver salts,additives,solvents,temperature and gas environment.And other investigations were conducted to explore the scope and limitations of this reaction under the optimal conditions.(3)Based on the related literatures and mechanism experiments,a reasonable mechanism of the synthesis of isoquinolines is proposed.That is,the Cp*Co(CO)I₂catalyst forms a cationic catalyst under the influence of Ag OTf,and then coordinates with the imine on the benzimidyl ester to activate the C-H bond to obtain a five-membered cobaltacycle intermediate.Next,sulfoxide Yelide takes off one molecule of DMSO to form a carbene.The pentavalent cobalt intermediate is obtained with the coordination of five-membered cobaltacycle intermediate and carbene,and the subsequent reaction is carbene inserts in carbon-cobalt bonds.Finally,the isoquinoline derivative is released after the pentavalent cobalt intermediate undergoes protonation and intramolecular nucleophilic attack.(4)Gram-scale experiments and further modification of isoquinoline derivatives show the potential application value of this reaction.