L-proline derivatives based on a calix[4]arene scaffold as chiral organocatalysts for the direct asymmetric aldol reaction in water

A new series of water-compatible proline catalysts (4-6) derived from calixarene bearing a hydrophobic nature have been synthesised. It was found that the compound 4 was a highly efficient organocatalyst for aldol reactions occurred in the water. Under optimised reaction conditions, high yields (up to 82%), good enantioselectivities (ee up to 81%) and high diastereoselectivities (dr up to 91:9) were obtained.