First example of the solvent effect on absolute conformation of chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones

Chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones (3S)-7 and (3S)-8 reveal solvent dependent conformational equilibria. The conformer with absolute P- conformation, with CH2X (X = p-tosyl, CI) group in a pseudoaxial (psi a) po sition and CH2OAc group in a pseudoequatorial (psi e) position, prevails in nonpolar solvents, as shown by LH-NMR and CD spectra. For (3S)-7 only a sm all shift of the conformational equilibrium in a polar solvent (DMSO) is ob served, whereas compound (3S)-8 inverts to a prevailing M-conformer. The in version barrier for MIP equilibrium is estimated on the bases of TDNMR data . For compounds (3R)-5 and (3S)-7, 8 the relative stability of the MIP conf ormers in the ground state is calculated by the MM2 method; comparison of t hese results with CD and H-1-NMR data reveal that nonpolar solvents invert the relative stability calculated for the two conformers. (C) 1999 Elsevier Science Ltd. All rights reserved.