Environmentally benign metal-free decarboxylative aldol and Mannich reactions

Baudoux, J; Lefebvre, P; Legay, R; Lasne, MC; Rouden, J

HERO ID

4933656

Reference Type

Journal Article

Year

2010

HERO ID 4933656
In Press No
Year 2010
Title Environmentally benign metal-free decarboxylative aldol and Mannich reactions
Authors Baudoux, J; Lefebvre, P; Legay, R; Lasne, MC; Rouden, J
Journal Green Chemistry
Volume 12
Issue 2 (2010)
Page Numbers 252-259
Abstract 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 [small beta]-amino esters or [small beta]-hydroxy esters including [small alpha]-substituted and [small alpha],[small alpha]-disubstituted ones in moderate to excellent yields. 1H 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 CO2 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.
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Keyword Anions; Temperature; Carboxylic acids; Solvents; NMR; green development; Carbon dioxide; Aldehydes; Esters