Comparison of Cu(II)-promoted leaving group stabilization of the cleavage of a homologous set of phosphate mono-, di-, and triesters in water, methanol, and ethanol

The cleavage of a set of phosphate mono-, di-, and triesters having a Cu(II)-complexed 2-phenanthrolyl group at the ortho-position of a departing phenoxide was studied in water and ethanol. Experimentally observed pH/rate profiles, solvent deuterium kinetic isotope effects, and activation parameters are compared with those obtained in methanol. The pH/rate profile in each solvent exhibits an extended plateau due to solvent attack on forms designated as Cu(II):1b/c](0) for the monoester, Cu(II):2b](+), for the diester, and Cu(II):3a](2+) for the triester. The solvent dkie values (k(H)/k(D)) for the three complexes are 0.91, 0.95, and 0.83 for decomposition of Cu(II):1b/c](0) in water (W), methanol (M), and ethanol (E), 1.22, 1.09, and 1.29 for Cu(II):2b](+) in W, M, and E, and 1.94, 2.2, and 1.96 for Cu(II):3a](2+) in W, M, and E. Near unit, or slightly inverse values for the monoester are taken as evidence for little involvement of solvent in a highly dissociative TS for P-OAr cleavage, with slightly higher solvent dkie values for the diester signifying the onset of some solvent participation in assisting the nucleophilic displacement. The larger primary dkie for the triester gives evidence for a solvent-assisted delivery of ROH in the cleavage through a more associative mechanism. Activation parameters for each substrate in the solvents are compared, indicating that the transition from methanol to ethanol for each substrate involves a near cancellation of the ΔΔH(?) and -TΔΔS(?) values (25 °C) so that the respective rates in both solvents are very similar. The transition from alcohol to water produces variable effects, with ΔΔH(?) and -TΔΔS(?) values canceling for cleavage of the triester and being additive for the mono and diester, explaining their 100-500 rate reduction in passing from methanol to water. The rate enhancing effects of the Cu(II)-promoted leaving group assistance in all three solvents are substantial and estimated at 10(12)-10(15) for the monoester, 10(12)-10(14) for the diester, and 10(5) for the triester relative to their background reactions.