Conformational preference in the side chain of compounds related to cortisone. Rotamer populations in some 21-substituted 20-oxo-steroids

Abstract

On the basis of the observed geminal coupling constant between non-equivalent 21-protons in series of 21-substituted 20-oxo-steroids (both in the presence and in the absence of 17α-substituents), rotamer populations about the 20,21-bond are calculated. The calculations are based on the π-contribution to geminal coupling and on a three-fold barrier to rotation, with conformations having a 21-substituent and the 20-oxo-group eclipsed corresponding to energy minima. When the 21-substituent is a halogen (X) the population of rotamers with C–X and CO eclipsed decreases in the order F > Cl > Br > l in the absence of a 17α-substituent. In the presence of a 17α-hydroxy-substituent, the same order holds but the corresponding populations are increased, especially for Br and I. Variation of the dielectric constant of the medium modifies the rotamer populations in accord with the anticipated changes in dipole–dipole interactions. In those cases where the temperature variations of the geminal coupling constant between 21-protons has been studied, the results are in accord with the relative stabilities of rotamers calculated on the basis of the π-contribution to geminal coupling alone.