Nucleophilic Additions to CO Double Bonds

Abstract

This chapter deals with the enantioselective aldol reaction which is the most advanced types of synthesis in the field of organocatalysis. During the last year, the organocatalysed aldol reactions have grown most remarkably, especially those which involve proline-derived organocatalysts, which provided uniformly spectacular stereoselectivities. From a green chemistry perspective, in comparison to the reasonable catalyst loading of 10 mol % generally applied to the enantioselective organocatalytic Michael reactions, there are a number of organocatalytic aldol reactions which could provide the corresponding aldol products in excellent stereoselectivities at lower catalyst loadings down to 0.1 mol %. Thus, a proline derivative bearing an imidazolium was shown to be capable at this remarkably low catalyst loading to induce excellent stereoselectivities in the aldol reaction of cyclohexanone with aldehydes under solvent-free conditions and, moreover, exceptionally high values of TON (up to 930) were achieved. Several other proline derivatives, such as 4-substituted acyloxyproline derivatives, were also successfully applied to the enantioselective aldolisation of cyclic ketones with substituted benzaldehydes in water at 0.5 mol % of catalyst loading. In addition to the highly efficient proline-derived organocatalysts, a wide number of chiral primary amines have been successfully applied as organocatalysts to promote enantioselective aldolisations, giving in most cases stereoselectivities as high as those obtained with the proline-derived catalysts. For example, a series of primary amine catalysts derived from chiral 1,2-cyclohexyldiamine provided excellent stereoselectivities for the aldolisation of ketones. Indeed, the results obtained for the asymmetric organocatalytic aldol reactions developed in the last year are unexpectedly and uniformly excellent.