Preparation and confinement effect of a heterogeneous 9-amino-9-deoxy-epi-cinchonidine organocatalyst for asymmetric aldol addition in aqueous medium

Abstract

A series of novel porous zirconium phosphonate-supported 9-amino-9-deoxy-epi-cinchonidines of general formulae Zr(OH)_4−2x(O₃PR)_x·nH₂O and Zr(HPO₄)_2−x(O₃PR)_x·nH₂O with the different arm chain lengths (n = 2–6) and mean diameters of approximately 20–40 nm have been prepared as heterogeneous organocatalysts. The different microtextures of zirconium phosphonates were also obtained by using template guest molecules, such as Et₃N, NaH₂PO₄ and sodium dodecyl benzene sulfonate. In the heterogeneous asymmetric aldol addition of p-nitrobenzaldehyde to cyclohexanone, excellent catalytic properties were achieved, especially in an aqueous medium. After completing the reaction, those zirconium phosphonate-supported 9-amino-9-deoxy-epi-cinchonidine organocatalysts could be readily recovered in quantitative yield by centrifugation or filtration, and reused for five consecutive runs without significant loss in catalytic performance. In particular, due to the steric confinement effect of the inorganic backbone, the single different configuration among possible four stereo-isomers in aldol adducts were favorably obtained, respectively depending on the interaction between the o-, m- or p-position of nitrobenzaldehyde and the backbone, which was never observed in homogeneous aldol addition.