Proline-Thiourea Self-Assemblies in Aldol Reactions

Significance

The proline-thiourea assembly-­catalyzed intermolecular aldol reaction of aromatic aldehydes with cyclohexanone is reported. The anti-configured products were obtained in high yields and exclusively excellent enantioselectivities. The reaction is proposed to proceed according to a modified Houk-List model, in which the carboxylate moiety of the proline forms an assembly with the thiourea, enhancing the reactivity and selectivity of the catalyst. Moreover, the thiourea acts as a nonpolar counterpart to proline, circumventing its solubility limits in unpolar solvents such as hexane or toluene.