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

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.