Configuration, stereodynamics and crystal structure of 3-substituted-2-oxofuro[2,3-b]indoles

Abstract

The molecular structure of 3a-alkyl-3-cyano-2-oxofuro[2,3-b]indoles 1a–d and 3a-alkyl-3-methoxycarbonyl-2-oxofuro[2,3-b]indoles 2a–c has been determined by ¹H NMR spectroscopy, X-ray diffraction and semiempirical (AM1) and abinitio (HF/3-21G* level) quantum chemical calculations. Considering detailed NOE measurements and the anisotropic effects of the C(3) carbonyl ester group, the preferred configurations were determined in solution. In these compounds the thermodynamic preference of the C(3) electron-attracting substituent for the endo or exo face appears to be controlled by the steric demand of the C(3a) alkyl substituent. The structurally folded furoindoles endo-2a–c evidence a repulsive interaction between the sterically crowding CO₂Me group and the π system of the benzene ring. An increase in the solvent polarity significantly alters the endo∶exo ratio in favor of the endo isomer. The solid-state structures of 1d and 2a demonstrate that these compounds assume configurations which differ in the spacial orientation of the C(3) substituent, with the CN group in 1d oriented to the endo face and the CO₂Me group in 2a to the exo face of the molecule, in agreement with those configurations determined in CD₂Cl₂ solution and from theoretical calculations.