KINETICS AND MECHANISM OF TETRAZOLE-CATALYZED PHOSPHORAMIDITE ALCOHOLYSIS

Kinetics of the tetrazole-catalyzed reaction of diisopropyl N,N-diisop ropylphosphoramidite (Ib) with tert-butyl alcohol has been studied by P-31 NMR spectroscopy in THF, and the results obtained have been compa red to those observed for the possible partial reactions involved, viz , the formation of diisopropyl tetrazolylphosphite (2b) and its subseq uent alcoholysis, The stoichiometry of the processes was first examine d with dimethyl N,N-diisopropylphosphoramidite (la) in MeCN. The tetra zole-promoted disappearance of Ib is as fast in the absence and in the presence of the alcohol: the alcoholysis of Ib is zero-order in the c oncentration of alcohol and second-order in the concentration of tetra zole, The reaction of Ib with tetrazole is independent of the concentr ation of the tetrazolide anion and second-order in that of tetrazole, while the reverse reaction, aminolysis of 2b is first-order in the con centration of the amine, The alcoholysis of 2b is, in turn, brst-order in the concentration of alcohol and second-order in that of tetrazole , but it also proceeds, although slowly, in the absence of tetrazole, The time-dependent product distribution of the alcoholysis of Ib shows intermediary accumulation of 2b, but at a lower level than could be p redicted by applying the rate constants determined independently for t he assumed partial reactions. Accordingly, tetrazole-catalyzed alcohol ysis of Ib is shown to proceed at least mainly via 2b, but an addition al pathway not involving 2b as an intermediate is proposed, Mechanisms of the partial reactions are discussed on the basis of the formal kin etics observed.