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

Article abstract of DOI:10.1021/jo00080a006

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 α-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 1a 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 (1.6 x 10⁶ folds for 3b over the rate in pure buffer), considerably larger than those in the presence of its nonmicellar analog (4.2 x 10⁴ folds) or of the free metal ion (1.5 x 10³ folds). However, in the case of unactivated esters, such kinetic benefits vanish out and the metal ion alone is even more effective (2 x 10⁴ folds acceleration for 31 in presence of Cu²⁺) than its complexes, either in the monomeric (7.3 x 10³ folds) or in the micellar form (4.6 x 10³ folds). On the basis of the possible changes in the mechanistic pathway depending on the nature of the leaving group, a rationale is offered.