The Conformational Preference of SomeTetrahydropyrrolo[1,2-d][1,3,4]oxadiazine Derivatives as Studied by NMR Spectroscopy and X-Ray Analysis

The diastereomeric (4S.4aS)-and (4R.4aS)-2.4-diphenyl-4H-4a,5,6,7-tetrahydropyrrolo[1,2-~[1,3,4]oxadiazines and their 2,4.4-triphenylsubstitutedanalog were synthesised.Their conformational behavior, elucidated by means of NMR spectroscopy and X-Ray analysis, revealed some surprising features.The unsubstituted parent compound (4aS)-2-phenyl- 4H-4a,5,6,7- tetrahydropyrrolo[l.2-d[1,3,4]oxadiazine was shown by X-Ray analysis to adopt the same conformational preference in the solid state as in solution, the cis N-Out conformation.However, both (4S.4aS)-2.4-diphenyI-4H-4a,5,6.7-tetrahydropyr-rolo[l,2-U][l,3,4]oxadiazine and its 2,4,4-triphenyl-substituted analog adopted a trans conformation in the solid state, in contrast to their predominant cis conformations adopted in solution.The determination of the conformation in solution required the examination of several parameters including homonuclear NOES, vicinal H,H and H.C coupling constants, the 2~H.7,,H.iavalue, the A6 H-7a,H-7P value, 6 H4a. and the ' 5 ~ chemical shifl of the bridgehead nitrogen.