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

The influence of a series of diamine ligands and alpha-amino acid ligands o n the rate and enantioselectivity of the Ni2+-and Cu2+-catalyzed Diels-Alde r reaction between 3-phenyl-1-(2-pyridyl)-2-propen-1-ones and cyclopentadie ne 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 subseq uent 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 interactio n between the aromatic ring of the alpha-amino acid ligand and the pyridine ring of the dienophile and for which quantitative evidence is provided. Th e same interaction also induces up to 74% enantioselectivity in the Diels-A lder reaction. This is the first example of enantioselectivity in a Lewis-a cid-catalyzed organic reaction in water. Most importantly, water significan tly enhances the enantioselectivity.