Phospho-Aldol Catalysis via Chiral Schiff Base Complexes of Aluminum

Abstract

Chiral complexes of aluminum containing the salcyen ligand framework, [(R,R)-salcyen]AlX (X = Me, OSiMe2tBu), catalyze the asymmetric addition of diorgano-H-phosphonates to carbonyls: the phospho-aldol reaction. Reaction proceeds smoothly at ambient temperature in various solvents and under aerobic conditions, to afford α-hydroxyphosphonate esters (MeO)2P(O)CHR(OH), with enantiomeric excesses (ee's) <50%. Although catalyst activity is linked to the nature of X, ee's appear to be only slightly affected. Substitution within the chiral salcyen ligand framework seems to affect ee principally where there is a steric or structural change near the metal center. Although catalysis is tolerant of small quantities of water, excess water leads to attenuation of enantioselectivity through decomposition of catalyst to afford hydrated aluminas which competes through achiral phospho-aldol catalysis. Kinetic analyses reveal a second-order polynomial relationship of the form x/([A0] − x)[A0] = k2t + k2t2, where [A0] is the initial concentration of H-phosphonate and carbonyl and x the degree of reaction. This may suggest that the metal complex must first be converted to another, more active precursor prior to catalytic turnover. Hammett analyses suggest that carbonyl binding to the metal center results in enhanced ee's, while single-crystal analyses on four aluminum complexes support the view that twisting of the ligand framework, as measured by the five-coordinate τ parameter, from a purely meridional geometry may be advantageous to stereoselectivity. Strategies for future developments are discussed in light of the results herein.