Study on the Transesterification of Methyl Aryl Phosphorothioates in Methanol Promoted by Cd(II), Mn(II), and a Synthetic Pd(II) Complex

Methanol solutions containing Cd(II), Mn(II), and a palladacycle, (dimethanol bis(N,N-dimethylbenzylamine-2C,N)palladium(II) (3), are shown to promote the methanolytic transesterification of O-methyl O-4-nitrophenyl phosphorothioate (2b) at 25 °C with impressive rate accelerations of 106−1011 over the background methoxide promoted reaction. A detailed mechanistic investigation of the methanolytic cleavage of 2ad having various leaving group aryl substitutions, and particularly the 4-nitrophenyl derivative (2b), catalyzed by Pd-complex 3 is presented. Plots of kobs versus palladacycle [3] demonstrate strong saturation binding to form 2b:3. Numerical fits of the kinetic data to a universal binding equation provide binding constants, Kb, and first order catalytic rate constants for the methanolysis reaction of the 2b:3 complex (kcat) which, when corrected for buffer effects, give corrected (kcatcorr) rate constants. A sigmoidal shaped plot of log(kcatcorr) versus sspH (in methanol) for the cleavage of 2b displays a broad sspH independent region from 5.6 ≤ sspH ≤ ∼10 with a kminimum = (1.45 ± 0.24) × 10−2 s−1 and a [lyoxide] dependent wing plateauing above a kinetically determined sspKa of 12.71 ± 0.17 to give a kmaximum = 7.1 ± 1.7 s−1. Brønsted plots were constructed for reaction of 2ad at sspH 8.7 and 14.1, corresponding to reaction in the midpoints of the low and high sspH plateaus. The Brønsted coefficients (βLG) are computed as −0.01 ± 0.03 and −0.86 ± 0.004 at low and high sspH, respectively. In the low sspH plateau, and under conditions of saturating 3, a solvent deuterium kinetic isotope effect of kH/kD = 1.17 ± 0.08 is observed; activation parameters (ΔHPd = 14.0 ± 0.6 kcal/mol and ΔSPd= −20 ± 2 cal/mol·K) were obtained for the 3-catalyzed cleavage reaction of 2b. Possible mechanisms are discussed for the reactions catalyzed by 3 at low and high sspH. This catalytic system is shown to promote the methanolytic cleavage of O,O-dimethyl phosphorothioate in CD3OD, producing (CD3O)2PO(S) with a half time for reaction of 34 min.