The conformational preference of some tetrahydropyrrolo[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-tetrahyd ropyrrolo[1,2-d][1,3,4]oxadiazines and their 2,4,4-triphenyl-substituted an alog were synthesised. Their conformational behavior, elucidated by means o f NMR spectroscopy and X-Ray analysis, revealed some surprising features. T he unsubstituted parent compound (4aS)-2-phenyl-4H-4a,5,6,7-tetrahydropyrro lo[1,2-d][1,3,4]oxadiazine was shown by X-Ray analysis to adopt the same co nformational preference in the solid state as in solution, the cis N-out co nformation. However, both (4S,4aS)-2,4-diphenyl-4H-4a,5,6,7-tetrahydropyr r olo[1,2-d][1,3,4]oxadiazine and its 2,4,4-triphenyl-substituted analog adop ted a trans conformation in the solid state, in contrast to their predomina nt cis conformations adopted in solution. The determination of the conforma tion in solution required the examination of several parameters including h omonuclear NOEs, vicinal H,H and H,C coupling constants, the (2)J(H-7 alpha ,H-7 beta) value, the Delta delta H-7 alpha,H-7 beta value, delta H4a, and the N-15 chemical shift of the bridgehead nitrogen.