Asymmetric aldol reactions between cyclic ketones and benzaldehyde catalyzed by chiral Zn2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane: effects of solvent and additives on the stereoselectivities of the aldol products

Abstract The direct aldol reaction between cyclic ketones and 4-nitrobenzaldehyde catalyzed by chiral Zn 2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane is reported. The anti -aldol products were mainly formed in cyclohexanone/ N -methylpyrrolidone(NMP)/MeOH with good diastereo- and enantioselectivity, while syn -aldol adducts were obtained as major products with good enantioselectivity in cyclohexanone/H 2 O and cyclohexanone/NMP/H 2 O. The fact that the UV/vis spectra of 2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate (Reichardt’s dye) were nearly identical in these solvent systems suggests that the switch in the relative configuration of the aldol products is induced by a large excess of H 2 O rather than the polarity of the solvent system. Furthermore, the addition of a small amount of TFA improved the enantioselectivity of the syn -aldol adducts produced in cyclohexanone/H 2 O with up to 92% ee ( anti / syn ratio = 30:70).