Copper-catalyzed C-C Bond Cleavage Of Unstrained Ketones For The Synthesis Of Piperidinyl Esters

The development of new strategies for the transformation of organic compounds has been one of the central interests in organic chemistry research.The carbon-carbon bond cleavage could reconstruct the carbon skeleton of the organic compound,achieving efficient synthesis of the complex compounds or the multi-functional compounds.In recent years,great attentions have been focused on the cleavage of C-C(CO)bond since carbonyl compounds,such as ketone and aldehyde,are widely existed in nature,and also commercially available or readily accessible through chemical synthesis.Developing transformation based on the carbon-carbon cleavage of ketone will undoubtedly enrich the toolbox for the utility of carbonyl compounds.Conventional methods for the carbon-carbon cleavage of ketones are mainly relied on the strained cyclic ketones.However,the synthesis of strained ketones is actually quite difficult.In contrast,the access and synthesis of unstrained ketones are much easier.From the energy point of view,due to the lack of ring-strain,carbon-carbon bond cleavage of unstrained ketone is full of challenge.In this paper,a method for the synthesis of carboxylic 2,2,6,6-tetramethyl-1-piperidinyl esters by copper-catalyzed cleavage of unstrained C-C bond from cyclic and acyclic ketones was developed.The research of this paper includes the following parts:In the first part,3-(2-Formyl-phenyl)-propionic acid 2,2,6,6-tetramethyl-piperidin-1-yl ester was synthesized by the reaction of 2-tetralone with 2,2,6,6-tetramethylpiperidine-1-oxyl(TEMPO).After extensive screening of reaction conditions(includes catalyst,ligand,solvent,temperature,and amine),the optimal conditions for the reaction were CuCl2·2H2O(10 mol%)as catalyst,1,10-phenanthroline monohydrate(20 mol%)as ligand,aniline(10 mol%),acetonitrile(2 mL)as solvent,40 ° C under air conditions.The second part discusses the substrate scopes of this transformation.Under the optimum conditions,different cyclic or acyclic ketones were smoothly transformed into the corresponding esters;TEMPO with different substituents at 4-position can also be compatible.In order to demonstrate the synthetic utility of the reaction,the target product 3-(2-formyl-phenyl)-propionic acid 2,2,6,6-tetramethyl-piperidin-1-yl ester was subjected to different conditions for further transformations.In the third part,the structures of products were characterized by 1H-NMR,13C-NMR,IR,high-resolution mass spectrometry and so on.In conclusion,we have developed a copper/air catalytic system for the cleavage of unstrained carbon-carbon bond of cyclic and acyclic ketones.The results of this research will enrich the toolbox for the utility of ?-aryl cyclic and acyclic ketones.