Chiral lipophilic ligands .3. Control of enantioselectivity in copper(II)-catalyzed cleavage of alpha-amino acid esters by aggregate morphology

The cleavage of the enantiomers of the p-nitrophenyl esters of phenylglicine (PhgPNP) was studied using chiral Cu(II) complexes of ligands 2 [2-N-R(1)-N-(1-R(2)-2-hydroxyethyl)aminomethylpyridine] as catalyst. Lipophilic ligands 2a,b (2a, R(1) = n-dodecyl, R(2) = methyl; 2b, R(1) = n-dodecyl, R(2) = isopropyl) were studied in aggregates of nonfunctional surfactants forming micelles (cationic, anionic, nonionic) or vesicles. With respect to the nonmicellar complex 2c . Cu(II) (2c, R(1) = methyl, R(2) = isopropyl), large rate accelerations (up to 400 times) and moderate (up to 11) enantioselectivities (as rate ratio between the faster and slower enantiomer) were found in cationic micelles. On the contrary, large inhibition was observed in anionic micelles, whereas in the nonionic ones the kinetic effects were negligible. In cationic vesicles the enantioselectivities are strongly influenced by the fluidity of the aggregate bilayer: remarkably large values (up to 26) were observed below the main phase transition temperature, T-c. The results were explained on the basis of different reaction mechanism due to the compartmentalization of the reacting species (a ternary complex ligand/Cu(II)/substrate) in different loci of the aggregate. It is suggested that the more lipophilic diastereomeric complex reacts with the substrate with attack of the Cu(II)-bound alkoxide of the ligand while the more hydrophilic one reacts with attack of a metal-bound hydroxyl of an exogenous water molecule. The first mechanism is both faster and more enantioselective.