Proline derivatives as organocatalysts for the aldol reaction in conventional and non-conventional reaction media

Abstract

Different l -proline derivatives were investigated as organocatalysts for the aldol condensation reaction between acetone and 4-nitrobenzaldehyde, in a conventional organic solvent (DMSO), in supercritical carbon dioxide, and in mixtures of this solvent and 1-allyl-3-alkyllimidazolium chlorides ionic liquids. The catalysts evaluated were: (S)-pyrrolidine-2-carboxylic acid ( l -proline), (R)-thiazolidine-4-carboxylic acid ( l -thioproline), (2S,4R)-4-[dimethyl(phenyl)silyl]oxy-pyrrolidine-2-carboxylic acid (dimethylphenylsilyloxy- l -proline), (2S,4R)-4-(tert-butyldimethylsilyl)oxy-pyrrolidine-2-carboxylic acid (butyldimethylsilyloxy- l -proline), and (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-[(S)-pyrrolidine-2-carboxamido]-tetrahydro-2H-pyran-2,4,5-triyl triacetate (peracetylated glucosamine- l -proline). One of the catalysts tested, the tert-butyldimethylsilyloxy- l -proline, was very effective, allowing lower reaction times, resulting in better yields and enantiomeric excesses than l -proline itself, both in organic solvent (DMSO) and in sc-CO 2 or a mixture of sc-CO 2 and ionic liquids. The use of the ionic liquid resulted in better yields and enantiomeric excesses in sc-CO 2 . The other catalysts tested were not as effective, resulting in yields and enantiomeric excesses similar or inferior to the ones obtained with l -proline.