Leaving group effect in the cleavage of picolinate esters catalyzed by hydroxy-functionalized metallomicelles

Micellar aggregates of complexes of transition metal ions with the hydroxy-functionalized surfactant 1a are very effective catalysts of the cleavage of activated esters of alpha-amino acids. To ascertain their effectiveness toward unactivated esters, a systematic kinetic study was undertaken employing as substrates the picolinic acid esters 3a-1, the pK(a) of their alcoholic portion spanning more than 12 units from 3.6 to 16. The leaving group effect was investigated in water, pH=6.3, in the absence and presence of CU2+ ions, in the presence of the nonmicellar complex 2-CU2+, and in the presence of micellar aggregates made of 1a-Cu2+ or of its O-methylated analog 1b-Cu2+. In the presence of free metal ions the leaving group effect is negligible in the case of esters with good leaving groups (pK(a)<ca. 12), and it becomes remarkably large in that of,unactivated substrates. In the presence of CU2+ complexes, either micellar la or nonmicellar 2, the leaving group effect is relatively small in the case of activated substrates (pK(a)<9, 1a; pK(a)<11, 2) and sharply increases in the case of unactivated substrates. A similar trend was observed in a less extensive kinetic investigation using Zn2+ ions at pH=7.5. The largest rate enhancements were observed in the case of the most activated substrates in micellar solutions of the 1a-Cu2+ complex (1.6x10(6) folds for 3b over the rate in pure buffer), considerably larger than those in the presence of its nonmicellar analog (4.2X10(4) folds) or of the free metal ion (1.5X10(3) folds). However, in the case of unactivated esters, such kinetic benefits vanish out and the metal ion alone is even more effective (2x10(4) folds acceleration for 31 in presence of CU2+) than its complexes, either in the monomeric (7.3x10(3) folds) or in the micellar form (4.6x10(3) folds). On the basis of the possible changes in the mechanistic pathway depending on the nature of the leaving group, a rationale is offered.