Addition of carbon centered radicals to methyl 3-(methylamino)acrylate: The regioselectivity of radical addition to enamino esters

The addition of carbon centered radicals to methyl 3-(methylamino)aminoacrylate has been investigated by means of DFT, using the hybrid-GGA B3LYP functional and the hybrid meta-GGAs MPWB1K and M052X, as well as post-HF restricted and unrestricted open-shell CBSB3-RAD computations. According to computations, in the gas phase methyl radical adds preferently to the C2 alpha-carbonyl position, but inclusion of solvation effects results in very close activation barriers for the two possible modes of attack. Electrophilic trifluoromethyl and phenyl radicals add preferently to the C2 position whereas in the case of the nucleophilic methoxymethyl radical the preferred site of addition depends on the initial conformation of the enamino ester. These results remark the strong ambiphilic nature of enaminone esters. (C) 2011 Elsevier B.V. All rights reserved.