Characterization of Transition States in Dichloro(1,4,7-triazacyclononane)copper(II)-Catalyzed Activated Phosphate Diester Hydrolysis

Abstract

The reaction mechanism for Cu[9]aneN3Cl2-catalyzed hydrolysis of ethyl 4-nitrophenyl phosphate was probed using kinetic isotope effects and isotope exchange experiments. The solvent deuterium isotope effect (Dk = 1.14), combined with the absence of 18O incorporation into 4-nitrophenol, suggests that hydrolysis proceeds through intramolecular attack of the metal-coordinated hydroxide at the phosphorus center. The secondary 15N isotope effect (15k = 1.0013 ± 0.0002) implies that loss of the leaving group occurs at the rate-limiting step with approximately 50% bond cleavage in the transition state. This study is one of the first applications of the secondary 15N isotope effect to simple metal-promoted hydrolysis reactions, and the result is consistent with concerted bond formation and cleavage. A mechanism consistent with the isotope studies is presented.