Study On The Construction Of Heterocyclic Compounds From O-alkenyl Aromatic Isocyanides

Nitrogen heterocyclic compounds have unique biological activities and pharmaceutical properties,which play an important role in the fields of chemistry,medicine,and materials.In recent years,the method to synthesize nitrogen heterocyclic compounds by using ortho-functionalized aryl isocyanides as a substrate has attracted much attention.Therefore,in this paper,transition metal catalyzed cyclizations with o-alkenyl aryl isocyanides containing-cyano group as starting materials were studied.These projects provided simple,mild and efficient methods to access nitrogen heterocyclic compounds.The main work includes the following two parts:Part I:The tandem cyclization reaction of o-alkenyl aryl isocyanides and diazonium compound was realized under copper catalysis.This reaction provides an efficient method for the synthesis of the pyrazolo[1,5-c]quinazoline.The molecular structure and molecular weight of the product were determined by ~1H NMR,¹³C NMR,HRMS,and X-raycrystallography.In addition,a gram-scale reaction was carried out with good yield under standard conditions.Intermediate capture experiment indirectly indicated that the[3+2]cycloaddition might be involved in this reaction.Based on this and related literature reports,a possible mechanism was proposed:two rings(imidazole ring and pyrimidine ring)and three new bonds were created through a domino reaction involving the[3+2]cyclization/elimination/intramolecular aza-addition sequence.Part II:The synthesis of high selectivity polysubstituted 3-cyanoindoles was realized via the Mn(III)-mediated radical cascade cyclization of o-alkenyl aromatic isocyanides with boronic acids.The molecular structures of the products were determined by ~1H NMR,¹³C NMR and HRMS,respectively.To gain some insight into the reaction mechanism,the following investigations:1)Radical inhibition experiments suggested a possible radical process for this reaction;2)H₂O¹⁸-labeling experiment has been carried out.The key elimination and coupling products were detected by GC-MS and TCL,indicating that water involved in the reaction.Based on the above results,a possible mechanism was proposed:the reaction involves a sequential intermolecular radical addition,intramolecular cyclization and cleavage of the C–C bond.