Visible Light-Mediated Palladium-Catalyzed Ring-Opening Deoxygenative Acylation Of Cyclobutanone Oxime Ester

Objective:Alkyl nitriles exist widely in bioactive drug molecules and natural products.In recent years,synthetic chemists have developed a series of methods for the construction of alkyl nitriles,in which the ring-opening functionalization of cyclobutanone oxime esters can efficiently construct a variety of substituted alkyl nitriles.So far,there are various strategies for ring-opening functionalization of cyclobutanone oxime ester,but most of the ester carbonyl groups of cyclobutanone oxime ester are used as leaving groups.The purpose of this study is to develop a method of ring-opening of cyclobutanone oxime ester and the ester group is deoxidized and used as acylating agent to construct a series of ketone-containing alkylnitriles.Methods:First of all,2-phenyl cyclobutanone oxime ester was used as the template substrate to screen the solvent,ligand,phosphine and other additives of the reaction,so as to determine the optimum conditions of the reaction.Then a series of aryl cyclobutanone oxime derivatives containing different substituents were prepared.under the optimum reaction conditions,the substrate range of the reaction was investigated,and the structure of the synthesized products was identified by NMR and high resolution mass spectrometry.Finally,through free radical verification experiment,competitive experiment and cross experiment,the reaction mechanism was explored and a possible reaction mechanism was proposed.Results:The optimum reaction conditions were determined as follows:2-phenyl cyclobutanone oxime ester（1.0 eq）as substrate,Ir[d F（CF₃）ppy]₂（dtbpy）PF₆（2 mol%）as photosensitizer,PPh₃（2.0 eq）as positive phosphine radical source,Pd（PPh₃）₄（5 mol%）as catalytic metal,DPEphos（6 mol%）as ligand,CH₃CN（0.1 M）as solvent,30W blue light irradiation for 24 hours at room temperature and argon atmosphere.Under the optimum reaction conditions,19 alkyl nitriles containing ketones were synthesized.These compounds can be easily converted into other functional groups,such as carboxylic acids,amines,esters and so on,which lays a foundation for organic synthesis and drug development.Conclusion:Palladium-catalyzed ring-opening of cyclohexanone oxime ester by visible light,and deoxidation by n-phosphine radical,resulting in the breaking of N-O bond,C-C bond and C-O bond and the formation of new C-C bond.A series of ketone-containing alkyl nitrile compounds can be synthesized without adding additional acylation reagent.This method enables ester group deoxidation to participate in acylation reaction under relatively mild conditions,which not only improves the reaction atom economy,but also provides a new and efficient strategy for acylation of alkyl nitrile.