Singlet Oxygen-Promoted Decarboxylative Amidation Of ?-Keto Acids With Free Amines

Amides are ubiquitous organic functional groups,as the backbone of proteins,not only play a crucial role in life but are also present in a great number of pharmacological active compounds and materials.Herein,the study on synthesis of amides has received considerable attention.The most prevalent strategy for preparing amides is the interconversion of amines with carboxylic acids or carboxylic acid derivatives,but due to the need to protect other functional groups fully,the lability of activated carboxylic acid derivatives and the low chemoselectivity makes a new generation of bond-forming reactions using acyl anion equivant increasingly attractive.Recently,?-keto acids have emerged as a new acyl anion reagent.Although decarboxylative coupling of ?-keto acids has been proven to be a powerful method for forming C–C bonds,oxidative coupling of ?-keto acids with amines for forming C–N bonds has been less explored.Herein,we developed a novel catalyst-free singlet oxygen-promoted decarboxylative amidation of ?-keto acids with amines under mild conditions.Advantages of the new protocol include avoidance of metal catalysts and high levels of functional group tolerance,expecially with tolerance of anilines containing electron-withdrawing groups or halide groups.In addition,the reaction can be scaled up.And the reaction also shows good chemical selectivity of amines to carboxyl groups with keto groups,and keto acids to amino groups with hydroxyl groups.Preliminary mechanistic studies reveale that mixing ?-keto acid with primary amine first leads to condensa-tion via the hemiaminal to ?-iminoacids,and then this reaction proceeds through oxidative decarboxyltion of ?-iminoacids to N-arylimidoyl radicals by singlet oxygen being generated under irradiation,next followed by hydrolysis to amides through a tautomerization of enol compounds.The ¹⁸O-labeled experiments demonstrate that the oxygen atom in the carbonyl functional group of amide originated from water in the solvent.Related oxidative de-carboxylative cross-coupling reactions promoted by photoexcited singlet oxygen are currently under investigation in our laboratory.