Nanosized metal or silicon oxides and L-proline or 4-hydroxy-L-proline in stereoselective synthesis of a dihydropyrimidinethione podand

The stereoselective Biginelli reaction involving a CH-active podand, thiourea, and benzaldehyde using nanosized metal oxides (NiO, Fe3O4, CuO, Al2O3, SiO2, and TiO2-SiO2), Bronsted acid, and commercially available chiral inductors (L-proline or 4-hydroxy-L-proline) was studied. The target dihydropyrimidinethione-containing podand was obtained with an enantiomeric excess of 70% and a moderate yield under mild conditions in the presence of nanooxide NiO and 4-hydroxy-L-proline. The adsorption of initial reactants and chiral inductor on the surface of nickel nanooxide was studied by IR spectroscopy. The activating and coordinating effect of the nanosized metal oxide on the initial reagents leading to an increasing the chemoselectivity and stereoselectivity of the Biginelli reaction was shown. On the basis of experimental data, one of the probable reaction mechanisms was proposed. This work further expanded the use of nanosized metal oxides in asymmetric catalysis and presented a new method for obtaining a valuable optically active podand with a 3,4-dihydropyrimidine-2-(1H)-thione moiety. Thus, the obtained results can be of interest for medicinal chemistry in the asymmetric one-step synthesis of other enantiomerically pure compounds.