Cobalt-catalyzed CH-activated Cyclization Of Allenes

Isoquinolin-1（2H）-one is an important structural unit,which is widely found in natural products and bioactive compounds.Isoquinolin-1（2H）-one has anti-tumor,anti-viral and blood pressure-lowering effects.It can be used as drugs to treat human diseases in the medical field.Meanwhile,it can also be used as probes and herbicides.Transition-metal-catalyzed C-H functionalization is one of the important methodologies to synthesize heterocyclic compounds.There are some problems of traditional transition-metal-catalyzed reaction,such as required pre-activation substrates,long synthetic route,harsh reaction conditions,relatively low yield.Synthesis of isoquinoline-1（2H）-one compounds via transition-metal-catalyzed C-H activation and cyclization reactions could overcome these problems.Transition-metal-catalyzed C-H activation and cyclization reactions assisted by the directing-group has become one of the research hotspots in the synthesis of heterocyclic compounds.Meanwhile,this method has been widely used in thesynthesis of some bioactive molecules.There are some advantages of transition-metal cobalt such as rich earth abundance,low price,low toxicity compared with other transition metals（Rh,Ru and Ir）.Cobalt-catalyzed C-H activation and cyclization reactions has been widely attention from scientists.Unsaturated hydrocarbon（e.g.alkenes,alkynes and arynes）as coupling partners in the C-H activation and cyclization reactions have made much remarkable progresses in the presence of transition-metal-cobalt catalyst.Allene is a class of unstable compounds containing two cumulative double bonds.Due to its structural particularity and reactivity,allene can be used as an intermediate for the synthesis of many natural products and medicinal compounds.It also has wide ranges of applications in the synthesis of biological active compounds and functional materials.Compared with alkenes and alkynes,there are few reports of allene employed in C-H activation and cyclization reactions because of its instability.Therefore,it is very important to develop a new method for the synthesis of isoquinolin-1（2H）-one from allene via cobalt-catalyzed C-H activation and cyclization reactions.Based on this,this paper mainly carries out the following work:（1）A series of 3,4-dihydroisoquinolin-1（2H）-ones were synthesized via C-H activation cyclization reaction using N-Cl-substituted benzamides and allenes as reaction substrates under the catalysis of transition metal cobalt,cesium acetate and silver acetate as additives,and trifluoroethanol as solvent.The method has the advantages of simple operation,mild conditions,easy availability of raw materials and good regioselectivity.（2）We made use of N-OPiv-substituted benzamides and allenes as reaction substrates under the catalysis of transition metal cobalt,cesium acetate and silver hexaflooroantimonate as additives and trifluoroethanol as solvent to generate 3,4-dihydroisoquinolin-1（2H）-ones.The method constructs C-C/C-N bond in one step,and has the advantages of wide substrate application range,simple operation and high atomic utilization.