Xanthene–prolinamide-based organocatalyst for asymmetric aldol reactions in green media

A novel organocatalyst, 14-(4-(pyrrolidine-2-carboxamido)phenyl)-14H-dibenzo[ a , j ]xanthene( 4-DBX ), was synthesized in four steps from commercially available starting materials and subsequently evaluated in asymmetric aldol reactions. Benzaldehyde derivatives and a variety of ketones were employed as aldol partners under environmentally friendly reaction conditions, including water, deep eutectic solvent, and high-speed ball milling. Under optimized reaction conditions, the catalyst (10 mol%) exhibited excellent performance in water, affording aldol products in quantitative yields (99% in 2.6 h), with enantiomeric excesses of up to 99% and diastereomeric ratios reaching 82:18. Overall, this method provides an efficient asymmetric aldol reaction of electron-deficient benzaldehydes in water. • A new xanthene–prolinamide organocatalyst ( 4-DBX ) was synthesized. • Excellent asymmetric aldol reactions were achieved in water without additives. • High enantioselectivity (up to 99% ee) and good diastereoselectivity (dr = 82:18) were obtained. • Efficient catalysis under green conditions including DES and ball milling. • Fast reactions delivered quantitative yields with low catalyst loading.