A green look at the aldol reaction

Aldol reactions have been and are widely applied for the preparation of beta-hydroxy aldehydes, beta-hydroxy ketones or alpha,beta-unsaturated aldehydes or ketones through addition or addition-elimination reactions of aldehydes and ketones. The study of the aldol reaction from the point of view of its greenness must have in mind first of all that a general synthetic method must be based on complete and efficient conversions of well defined selectivity and that greenness is more a term for comparison than an absolute kind of qualification. This comparison, when referred to the aldol reaction, applies here to the diverse modifications of the reaction. Thus, the original poorly selective, but highly atom economic catalytic procedures, have been improved by several authors by introduction of stoichiometric forms of activation in the search for better selectivities. However, the success in these improvements has been accompanied by higher levels of hazard and waste. The study of the greenness of the aldol reaction is completed by a short overview of recent contributions intended to achieve efficient, safe and clean conversions that are susceptible to becoming general green synthetic procedures. Interesting contributions are highlighted for reactions carried out under solvent-less conditions, in water, ionic liquids and supercritical fluids, with activation by microwaves, or with use of heterogeneous catalysis and especially of biocatalysis and biomimetic catalysis. Promising methods based on reduction of unsaturated ketones or on rearrangement of allylic alcohols have also recently been described.