Palladium-catalyzed Decarboxylative Cross-coupling Of Aryl Carboxylic Acids With Unsaturated Piperidones

The piperidones moiety is a common motif in bioactive natural products andpharmaceutical compounds.The piperidones, especially the2,3-dihydro-4-pyridones,also attract the attention in pharmaceutical development as a kind of importantintermediates in the pharmaceutical industry for there are a plethora of chemoselectivetransformations about the6-membered enaminones.Over the past30years, the Pd-catalyzed cross-coupling has achieved a series ofaccomplishments, and the conventional reaction between the aryl halides and theolefins is also well-documented.The cross-coupling reaction between theheteroaromatics and benzoic acids, however, is few.On the achievements of the Pd-catalyzed decarboxylative coupling of thiazolesand benzoxazole with various substituted benzoic acid,we strive for a reaction of thePd-catalyzed unsaturated piperidones with the aryl carboxylic acid.The involvedworks we have obtained are:(1) A series of model experiments are employed to find out the optimizedconditions that range from the catalyst, ligand, solvent, temperature to the ratio of thereagent and the expected products are obtained.(2) A variety of methoxy-substituted aryl carboxylic acid are employed to reactwith the unsaturated piperidones and5new compounds are obtained.(3) On the purpose of broadening the scope of our reaction, the unsaturatedpiperidones are choosed to react with the nitro-substitued carboxylic acid.(4) Two proposed mechanism of the cross-coupling between the unsaturatedpiperidones and substitued aryl carboxylic acid are presented according to the resultsobtained.In summary, a Pd-catalyzed decarboxylative coupling between the unsaturatedpiperidones and aryl carboxylic acid is developed. The reaction are high atom-economical and avoid waste fromation for the CO2are the only products during thedecarboxylation process which provide the reference for the ongoing related research.