COMPUTATIONAL STUDY OF THE EFFECT OF CONFIGURATION AND THE DEGREE OF SUBSTITUTION AT N IN N-]O AND O-]N ACYL MIGRATION IN DIASTEREOISOMERS OF 3-AMINO-1,2,3-TRIPHENYLPROPANOL

Using molecular mechanics (MM2, MM3) and semiempirical molecular orbit al methods (EHMO, AM1, PM3) the relative energies were estimated from models for the tetrahedral intermediates in N --> O and O --> N acyl m igration in diastereo-isomers of 3-amino-1,2,3-triphenylpropanol to ch eck the necessity of invoking a stereoelectronic effect to explain the ir reactivities. The molecular mechanics results correctly reproduce t he greater steric hindrance expected from phenyl/OH and phenyl/CH3 dia xial interactions in the models for the tetrahedral intermediates of t he reactions for converting the rel-(1R,2S,3R)-3-acetamido-1,2,3-triph enylpropanol and, respectively, S)-3-(N-methylaceta-mido)-1,2,3-triphe nylpropanol, into the corresponding amino and methylamino esters. Resu lts from computations with the COSMO continuum solvation model, as app lied to the semiempirical AM1 Hamiltonian, show that in all cases the intermediates with the N-H, respectively N-CH3, axial are stronger sta bilized by the solvent, thus casting doubt on the exclusive role of th e stereoelectronic effect in this case.