Demonstration of Prominent Cu(II)-Promoted Leaving Group Stabilization of the Cleavage of a Homologous Set of Phosphate Mono-, Di-, and Triesters in Methanol

A series of phosphate mono-, di-, and triesters with a common leaving group (LG) (2′-(2-phenoxy)-1,10-phenanthroline) was prepared, and the kinetics of decomposition of their Cu(II) complexes was studied in methanol at 25 °C under s spH-controlled conditions. The Cu(II) complexes of 2-[2′-phenanthrolyl]phenyl phosphate (Cu(II):6), 2-[2′-phenanthrolyl]phenyl methyl phosphate (Cu(II):7), and 2-[2′-phenanthrolyl]phenyl dimethyl phosphate (Cu(II):8) are tightly bound, having dissociation constants K d ≤ 3 × 10−7 M, with the Cu(II) being in contact with the departing phenoxide. The s spH/rate profile for cleavage of Cu(II):6 has a low s spH plateau (k o = 6.3 × 10−3 s−1), followed by a bell-shaped maximum (k cat max = 14.7 ± 0.4 s−1) dependent on two ionizations with s spK a 2 and s spK a 3 = 7.8 ± 0.1 and 11.8 ± 0.2. The s spH/rate profile for cleavage of Cu(II):7 has a broad plateau from s spH 3 to s spH 10 followed by a descending wing at higher s spH with a gradient of −2. The s spH/rate profile for cleavage of Cu(II):8 is sigmoidal with two plateaus (k 1 = (2.0 ± 0.2) × 10−5 s−1, k 2 = (1.2 ± 0.2) × 10−6 s−1), connected by an ionization with a s spK a of 6.03. Activation parameters are given for the reactions in the plateau regions: all three species show similar ΔH ⧧ terms of 21.4−21.6 kcal/mol, with major differences in the ΔS ⧧ terms, which vary from 18 to 2.3 to −7.4 cal/(mol·K) passing from the mono- to di- to triester. Detailed analyses of the kinetics indicate that the reactions involve spontaneous solvent-mediated cleavage of the Cu(II)-coordinated phosphate dianion [Cu(II):6b]0 and phosphate diester monoanion [Cu(II):7b]+ and, for the triester, complexes containing Cu(II) and Cu(II):−OCH3 designated as [Cu(II):8a]2+ and [Cu(II):8b]+. Reactions where methoxide is the active nucleophile are not observed. Comparisons of the rates of the decomposition of these species at their s spH maxima in the neutral s spH region with the estimated rates of the background reactions indicate that leaving group assistance provided by the coordinated Cu(II) accelerates the cleavage of the phosphate mono-, di-, and triesters by 1014 to 1015, 1014, and 105. Detailed Hyperquad 2000 analysis of titration data indicates that phenoxide 9 − is bound 23 kcal/mol stronger than the phosphate triester 8. It is the realization of part of this energy in the emerging products resulting from P−O(LG) cleavage that provides the driving force for the catalyzed reactions.