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

Abstract

The stereoselective Biginelli reaction involving a CH-active podand, thiourea, and benzaldehyde using nanosized metal oxides (NiO, Fe 3 O 4 , CuO, Al 2 O 3 , SiO 2 , and TiO 2 -SiO 2 ), Brönsted 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

Asymmetric Synthesis of Dihydropyrimidinethione Podand in the Presence of C2‐Symmetric Bis(Hydroxy)Proline‐Containing Amides

“…The HPLC chromatogram of podand 6 (Figure 3a) shows the formation of a racemic mixture of R , R ‐ and S , S ‐enantiomers ( t r =19.43 (peak A) and 24.55 min (peak C)) and meso form 6 b ( t r =21.93 min (peak B)) with a ratio of 1 : 2 : 1. The results [23b] previously obtained and described by us suggest that the stereoselective synthesis of podand 6 in the presence of 4‐hydroxy‐ L ‐proline leads to an excess of ( R , R )‐enantiomer 6 a , corresponding to peak A in the HPLC chromatogram (Figure 3b), while in the synthesis involving L ‐proline, the ( S , S )‐enantiomer 6 c , corresponding to peak C, predominates (Figure 3c).…”

“…Taking into account the acidity of the medium (Table 3) and previously obtained data, [22b,23b] we considered one of the likely mechanisms for the stereoselective synthesis of enantiomerically enriched product 6 , as shown in Scheme 2. Note that the catalytic activity of chiral inducer 10 b is manifested due to the formation of salt form 23 in the presence of trifluoroacetic acid, according to the literature data [22]…”