A systematic study of ligand effects on a Lewis-acid-catalyzed Diels-Alder reaction in water. Water-enhanced enantioselectivity

The influence of a series of diamine ligands and alpha-amino acid ligands on the rate and enantioselectivity of the Ni2+-and Cu2+-catalyzed Diels-Alder reaction between 3-phenyl-1-(2-pyridyl)-2-propen-1-ones and cyclopentadiene in water has been investigated. Equilibrium constants and enthalpies and entropies for binding of the dienophile to the catalyst-ligand complex as well as rate constants, activation enthalpies, and entropies for the subsequent reaction with the diene have been determined using UV-vis spectroscopy. Ligand-accelerated catalysis is observed for several aromatic alpha-amino acid ligands. This is likely to be a consequence of arene-arene interaction between the aromatic ring of the alpha-amino acid ligand and the pyridine ring of the dienophile and for which quantitative evidence is provided. The same interaction also induces up to 74% enantioselectivity in the Diels-Alder reaction. This is the first example of enantioselectivity in a Lewis-acid-catalyzed organic reaction in water. Most importantly, water significantly enhances the enantioselectivity.