Environmentally benign metal-free decarboxylative aldol and Mannich reactions

Aiming at the development of green and efficient C-C bond formations ( aldol and Mannich reactions), the decarboxylative nucleophilic addition of malonic acid half ester to imines or aldehydes under mild metal-free conditions was studied. A careful control of the temperature and the appropriate choice of the organic base allowed us to obtain beta-amino esters or beta-hydroxy esters including alpha-substituted and alpha,alpha-disubstituted ones in moderate to excellent yields. (1)H NMR monitoring of the reaction unveiled two distinct mechanisms depending on the hemimalonate used. With the unsubstituted substrate, a carboxylic acid intermediate was isolated upon acid quench resulting from the nucleophilic addition of the putative enol carboxylate anion of the hemimalonate to imines/aldehydes before CO(2) loss. With substituted hemimalonates, the reaction likely involved an enolate which then added to imines/aldehydes or was competitively protonated. According to the base used, the reaction can be carried out either under solvent free-conditions or in an ionic liquid under mild conditions.