CHIRAL LIPOPHILIC LIGANDS .1. ENANTIOSELECTIVE CLEAVAGE OF ALPHA-AMINO-ACID ESTERS IN METALLOMICELLAR AGGREGATES

Several chiral ligands (1a,b, 2a-d), their marked lipophilic structure featuring a binding subunit comprising a 2-substituted pyridine, a te rtiary amine, and a hydroxyl, have been synthesized and their complexe s with Cu(II), Zn(II), or Co(II) ions investigated in homomicellar or comicellar aggregates as enantioselective catalysts of the cleavage of p-nitrophenyl esters of alpha-amino acids (Phe, Phg, Leu). Rate accel erations up to 3 orders of magnitude over the Cu(II) catalyzed hydroly sis and enantioselectivities ranging from; 3.2 to 11.6 have been obser ved. In each case explored, the chiral ligand reacts faster with the e nantiomeric substrate of opposite absolute configuration. Several piec es of evidence indicate that the effective cleavage process in micella r aggregates involves the following: (a) the formation of a ternary (l igand-metal ion-substrate) complex; (b) within such a complex, a nucle ophilic attack of the ligand hydroxyl on the substrate to give a trans acylation intermediate; and (c) the metal ion promoted hydrolysis of t he transacylation intermediate with a relatively fast turnover of the catalyst. Such a mode of action does not operate outside or in the abs ence of micellar aggregates: in this case; the hydroxyl is displaced b y water that acts as the nucleophile ina slower (less enantioselective ) process. The enantioselectivity of the transacylation process appear s to be little affected by the steric interaction between the substitu ents at the chiral center of the amino acid ester and of the ligand. W e suggest that the enantioselectivity arises from a different hydratio n, due to steric reasons, of the diastereomeric complexes comprising t he two enantiomers of the substrate. As a consequence, the relevance o f the competing mechanisms of cleavage of the ester, the first one, fa ster, involving the hydroxyl and the second one, slower, involving a C u(II)-bound water molecule, may be different. In the case of the less hydrated, more hydrophobic R-S or S-R complex the former, faster, mode of cleavage may be more relevant than in the case of the more hydrate d, less hydrophobic, S-S or R-R complex.