A Systematic Study of Ligand Effects on a Lewis-Acid-Catalyzed Diels−Alder Reaction in Water. Water-Enhanced Enantioselectivity

Abstract

The influence of a series of diamine ligands and α-amino acid ligands on the rate and enantioselectivity of the Ni 2+ - and Cu 2+ -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 α-amino acid ligands. This is likely to be a consequence of arene−arene interaction between the aromatic ring of the α-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.