Enantioselective cleavage of activated amino acid esters promoted by chiral palladacycles

The ester cleavage of R- and S-isomers N-CBZ-leucine p-nitrophenyl ester intermolecularly catalyzed by R- (a) and S-stereoisomers (b) of the Pd(II) metallacycle [Pd(C6H4C*HMeNMe2)Cl(py)] (3) follows the rate expression k(obs) = k(o) + k(cat)[3], where the rate constants k(cat) equal 25.8 +/- 0.4 and 7.6 +/- 0.5 dm(3) mol(-1) s(-1) for the S- and R-ester, respectively, in the case of 3a, but are 5.7 +/- 0.6 and 26.7 +/- 0.5 dm(3) mol(-1) s(-1) for the S- and R-ester, respectively, in the case of 3b (pH 6.23 and 25 degrees C). Thus, the best catalysis occurs when the asymmetric carbons of the leucine ester and Pd(LI) complex are R and S, or S and R configured, respectively. Molecular modeling suggests that the stereoselection results from the spatial interaction between the CH2CHMe2 radical of the ester and the alpha-methyl group of 3. A hydrophobic/stacking contact between the leaving 4-nitrophenolate and the coordinated pyridine also seems to play a role. Less efficient intramolecular enantioselection was observed for the hydrolysis of N-t-BOC-S-methionine p-nitrophenyl ester with R- and S-enantiomers of [Pd(C6H4C * HMeNMe2)Cl] coordinated to sulfur. (C) 1998 Elsevier Science S.A. All rights reserved.