Conformational stability of atropisomeric 1-naphthylcarbinols and 1-(1-naphthyl)ethylamines

The stereodynamics of atropisomeric 1-naphthylcarbinols and 1-(1-naphthyl)ethylamines exhibiting two stereogenic elements, i.e. a chiral center and a chiral axis, were investigated. PM3 calculations suggest that these atropisomers populate two major conformations bearing the most sterically demanding group perpendicular to the naphthalene moiety. Due to its high conformational stability, the atropisomers of 1-(1-naphthyl)-2,2-dimethyl-1-propanol can be separated by HPLC at room temperature. Kinetic studies revealed a free energy of activation for rotation about the chiral axis of 158 kJ/mol. Incorporation of less bulky substituents into the stereogenic center of this class of atropisomers results in significantly reduced steric hindrance to isomerization. The conformational stability of N,N′-dibutyl-1-(1-naphthyl)ethylamine was determined as 75.9 kJ/mol by variable-temperature NMR spectroscopy.