| Alkyl carboxylic acid is a basic structural unit in life sciences and an important raw material in the chemical industry.It occupies an important position in the pharmaceutical,additive and other industries.Among the reaction types of carboxylic acid and its derivatives,decarboxylation is a very important type of reaction.Through decarboxylation and a series of subsequent reactions such as coupling,a series of reactions can be initiated by the growth or reduction of the carbon chain or by the alkyl radicals after decarboxylation..Since the traditional type of decarboxylation reaction requires relatively severe reaction conditions or has certain requirements on the structure and electrical properties of the reaction substrate,or requires the use of expensive or toxic reagents,its practical application will be limited.In this case,N-hydroxyphthalimide ester(NHPI)with redox activity came into being.Among all the reaction types of NHPI,decarboxylation C-C coupling is the most important and basic type of reaction,especially C(spp)-C(sp3),which is used for the alkylation of small molecules,has a certain expansion value.Methyl is an important regulatory group in biomass and drug molecules,and it can enhance its activity by regulating the interaction of biologically active molecules with their target proteins.The conversion of carboxyl and its derivative functional groups to methyl is a practical reaction method in medicinal chemistry.We envisaged a decarboxylation coupling reaction catalyzed by cobalt to achieve methylation through redox active carboxylic acid esters(RAEs)and mild trimethylaluminum reagents,which can avoid the complex side effects caused by redox fluctuations.Reaction,this is also different from the conventional reduction method of converting carboxyl groups to methyl groups.This catalytic reaction system has good compatibility and is suitable for various primary and secondary alkyl RAEs,including functional groups commonly used for cross-coupling(such as aryl and alkyl bromide,chlorine,aryl boronicacidpinacolester,etc.),nitrogen-containing heterocycles,etc.,have also used this method to successfully synthesize a variety of methylated products,especially the late modification and derivative products of some natural products.The reaction is realized by a catalytic cycle of decarboxylation,oxidative addition,and reduction elimination by the methyl group in the trimethylaluminum coordinated with the cobalt center and undergoes single electron transfer(SET)with the substrate RAEs.Free radical reaction,in which the choice of bidentate phosphine ligand and solvent polarity is the key to the successful conversion of the reaction. |
