The Regioselective Construction Of Isoquinolones Via Rh(Ⅲ)-catalyzed C-H Bond Activation Annulation Of Propargylic Alcohol Derivatives With N-hydroxybenzamide

Nitrogen-containing heterocyclic compounds have attracted much attention as important skeletons of natural products,bioactive molecules and drug molecules.In recent years,the development of efficient and novel methods for the construction of nitrogen-containing heterocycles has been a research hotspot in the field of organic synthesis and drug synthesis.Propargylic carbonates and propargylic alcohol are often used as C1,C2 or C3 synthons in organic synthesis.Under the catalysis of transition-metals,they interact with nucleophilic nitrogen-containing groups to construct a series of nitrogen-containing heterocyclic compounds with biological or pharmacological activities.In this paper,the research progress of efficient synthesis of nitrogen-containing heterocyclic compounds by alkyne insertion/cyclization of propargylic carbonates and propargylic alcohol is reviewed.Based on the previous research of our group,the regioselective synthesis of isoquinolinones by taking advantage of rhodium-catalyzed cyclization of propargylic alcohols derivatives was developed by using regioselective coordination of carbonyl oxygen in propargylic carbonate and hydroxyl oxygen in propargylic alcohols with rhodium as catalyst,the specific research contents are as follows:Rhodium[RhCp*Cl₂]₂catalyzed regioselective synthesis of 3-arylisoquinolinone derivatives from propargylic acetates and N-hydroxybenzamide by alkyne insertion/intramolecular cyclization was studied.Thirty-three 3-arylisoquinoline-1（2H）-one were synthesized by C-H functionalization of N-hydroxybenzamide and insertion cyclization of propargylic acetate and all the products were characterized by¹H NMR and¹³C NMR.After the structure of 3-arylisoquinoline-1（2H）-one was confirmed by 1H-NMR,13C-NMR and X-ray single crystal diffraction data,the reaction conditions were optimized,and the effects of electronic and steric hindrance of different substituent group on the reaction were studied,Moreover,the results of the intermolecular competition experiment further show that the electronic effect of the substituent has an effect on the reaction.The subsequent deuterization experiment and kinetic isotope experiment results show that C-H bond is easy to crack and reversible,and the C-H cracking process may not be the rate-determining step of the reaction,while the scale-up experiment further shows the practicability of this method.Combined with the experimental results and literature research,a possible reaction mechanism of the reaction is proposed.The developed method requires simple raw materials,good substrate adaptability,high regioselectivity and only water as by-product,which reflects the environmental friendliness.Rhodium[RhCp*Cl₂]₂catalyzed regioselective synthesis of 3-acyl-isoquinoline-1（2H）-ketones derivatives from propargylic alcohol and N-hydroxybenzamide by alkyne insertion/intramolecular cyclization was studied,effectively synthesizing 20 3-acylisoquinoline-1（2H）-one compounds.After the structure of 3-acylisoquinoline-1（2H）-one was confirmed by ¹H NMR,¹³C NMR and X-ray single crystal diffraction data,the reaction conditions were optimized,and then carry out the research of the universality of the substrate under the optimal experimental conditions,and further study the effects of electronic and steric hindrance of different substituent group on the reaction.Finally,a possible catalytic cycle mechanism for the reaction was proposed based on the existing literature and experimental results.The developed method has the advantages of simple operation,mild reaction conditions,good substituent group compatibility,without external oxidants and high regioselectivity.