Enantioselective autocatalysis. III. Configurational and conformational studies on a 1,4-benzodiazepinooxazole derivative

We report here on configurational and conformational studies undertaken on the bromofluoro-1,4-benzodiazepinooxazole derivative I, which has previously been found capable of undergoing total spontaneous resolution under racemizing conditions. Due to its bridgehead N-atom I may exist in any of four diastereomeric forms, CN (or CN) and CN (or CN). Molecular mechanics calculations revealed that in their lowest energy conformations the CN (or CN) diastereomers were favored over the CN (or CN) diastereomers by some 3.42 kcal/mol, while semi-empirical quantum mechanical calculations indicated heats of formation also favoring the CN (or CN) diastereomers by 3.83 kcal/mol. TheH NMR spectra of the three crystalline modifications (α, β and γ) of I were examined in acetone, and found to be identical. These data, combined with the results of the above calculations, suggest that I exists in methanol or methanol-acetone solutions as the CN (or CN) enantiomer prior to its racemization. © 1995 Kluwer Academic Publishers.