Steric size in conformational analysis. Steric compression analyzed by circular dichroism spectroscopy

The relative steric size of methyl, ethyl, isopropyl, tert-butyl, phenyl, and benzyl groups has been determined from a sensitive tetrapyrrole model and exciton coupling circular dichroism (CD) measurements. Unlike the classical cyclohexane model, from which the relative steric demand of functional groups has been assessed quantitatively (A-values) and is based on the preference for equatorial vs axial orientations, the bilirubin model assesses substituent size from head-to-head steric compression. Thus, exciton CD amplitudes of a set of sensitive anti-chiral alpha (R/S)-substituted-beta'(S)-methylmesobilirubins-XIII alpha (1-6) suggests an apparent relative steric size: tert-butyl similar to isopropyl > phenyl similar to ethyl > benzyl > methyl. The order is somewhat different from that obtained by measuring equatorial vs axial configuration preferences on substituted cyclohexanes by NMR spectroscopy: tert-butyl much greater than phenyl > isopropyl > ethyl similar to benzyl similar to methyl.