Nature http://doi.org/6kb (2015)
In line with the known stability of amides, previous approaches to this type of transformation have required the use of harsh acidic or basic conditions and a large excess of alcohol nucleophile — often used as reaction solvent. And, although metal-catalysed activation of carbon–heteroatom bonds in other carbonyl compounds has been reported, activation of the C–N bond in amides has not. Building upon their prior work on the activation of strong aryl–heteroatom bonds, Garg and co-workers turned to nickel catalysis. They began their study by performing density functional theory calculations to determine both the free-energy change for the methanolysis of a variety of N-substituted benzamides, and also the activation barrier for oxidative addition of the amide to an N-heterocyclic carbene–nickel catalyst. The calculations suggested that methanolysis of N-methyl-N-phenylbenzamides would be favourable both thermodynamically and kinetically and this was borne out experimentally — with the reaction producing an excellent yield of ester using only a small excess of methanol at just 80 °C.
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