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 α( R/S )-substituted-β‘( S )-methylmesobilirubins-XIIIα ( 1 − 6 ) suggests an apparent relative steric size: tert -butyl ∼ isopropyl > phenyl ∼ 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 ≫ phenyl > isopropyl > ethyl ∼ benzyl ∼ methyl.