10.1039/b419335k
The research details the development of a new class of chiral 4-(pyrrolidino)-pyridine catalysts derived from (S)-proline for the kinetic resolution of sec-alcohols. These catalysts, including compounds 4 and 5, leverage both van der Waals (π) and H-bonding interactions to achieve enantioselective acylation. The study involved synthesizing these catalysts from simple starting materials like 3-carboxy-4-chloropyridine and various amines. The catalysts were evaluated in the kinetic resolution of mono-protected diols in the presence of isobutyric anhydride, with the (S)-prolinol-derived catalysts showing significant enantioselectivity. The hydroxyl group in these catalysts was found to play a crucial role in determining the selectivity of the acylation reactions. The researchers also explored the influence of different substituents and the impact of H-bonding on the selectivity, using NMR spectroscopy to investigate possible aryl-pyridinium ion π-stacking interactions. The findings suggest that these catalysts represent a novel approach to achieving remote stereochemical control in acylation reactions, with potential applications in enantioselective acyl-transfer processes.