CONFORMATIONAL-ANALYSIS OF SUBSTITUTED HEXAHYDROPYRROLO[2,3-B]INDOLES AND RELATED SYSTEMS - AN UNUSUAL EXAMPLE OF HINDERED ROTATION ABOUT SULFONAMIDE S-N BONDS - AN X-RAY CRYSTALLOGRAPHIC AND NMR-STUDY

An indepth comparison of the solution (CDCl3, H-1-NMR) and solid state (X-ray) conformations of the hexahydropyrrolo[2,3-b]indoles 4, 5, and 6 is made. Close parallels with the literature conformations of the aflatoxin furo[2,3-b]benzofuran skeleton and with the conformation of the naturally occuring hexahydropyrrolindole physostigmine are noted. In the solid state the suIfonamide N in 4 - 6 is non-planar with various degrees of rotation about the S-N bond. In solution, variable temperature H-1-NMR evidence indicates hindered rotation about the N-S bond of the sulfonamide group in 4 - 6, possibly coupled to inversion of the pyramidal suIfonamide N atom. Reaction of 5 with LDA followed by quenching with methyl iodide resulted in alkylation with clean inversion of configuration.