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

Article abstract of DOI:10.1016/0040-4020(95)00001-O

An indepth comparison of the solution (CDCl₃, ¹H-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 occurring hexahydropyrrolindole physostigmine are noted. In the solid state the sulfonamide N in 4-6 is non-planar with various degrees of rotation about the S-N bond. In solution, variable temperature ¹H-NMR evidence indicates hindered rotation about the N-S bond of the sulfonamide group in 4-6, possibly coupled to inversion of the pyramidal sulfonamide N atom. Reaction of 5 with LDA followed by quenching with methyl iodide resulted in alkylation with clean inversion of configuration.