Chiral Lipophilic Ligands. 1. Enantioselective Cleavage of α-Amino Acid Esters in Metallomicellar Aggregates

Article abstract of DOI:10.1021/jo00094a034

Several chiral ligands (1a,b, 2a-d), their marked lipophilic structure featuring a binding subunit comprising a 2-substituted pyridine, a tertiary amine, and a hydroxyl, have been synthesized and their complexes 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 α-amino acids (Phe, Phg, Leu).Rate accelerations up to 3 orders of magnitude over the Cu(II) catalyzed hydrolysis and enantioselectivities ranging from 3.2 to 11.6 have been observed.In each case explored, the chiral ligand reacts faster with the enantiomeric substrate of oposite absolute configuration.Several pieces of evidence indicate that the effective cleavage process in micellar aggregates involves the following: (a) the formation of a ternary (ligand-metal ion-substrate) complex; (b) within such a complex, a nucleophilic attack of the ligand hydroxyl on the substrate to give a transacylation intermediate; and (c) the metal ion promoted hydrolysis of the transacylation intermediate with a relatively fast turnover of the catalyst.Such a mode of action does not operate outside or in the absence of micellar aggregates: in this case, the hydroxyl is displaced by water that acts as the nucleophile in a slower (less enantioselective) process.The enantioselectivity of the transacylation process appears to be little affected by the steric interaction between the substituents at the chiral center of the amino acid ester and of the ligand.We suggest that the enantioselectivity arises from a different hydration, due to steric reasons, of the diastereomeric complexes comprising the two enantiomers of the substrate.As a consequence, the relevance of the competing mechanisms of cleavage of the ester, the first one, faster, involving the hydroxyl and the second one, slower, involving a Cu(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 hydrated, less hydrophobic, S-S or R-R complex.