Atropisomerism about aryl–C(sp3) bonds: chemically driven rotational pathway in cannabidiol derivatives

Abstract

The conformational behaviour arising from the restricted C(sp²)–C(sp³) axis in ortho O-substituted naphthylcyclohexane and naphthylcyclohexene oxide derivatives of cannabidiol was examined by means of VT-NMR experiments and DFT calculations. Atropisomeric compounds with barriers in the range of 91.1 to 95.1 kJ mol⁻¹ were obtained at 298 K. Two possible transition states (TS1 and TS2) were located, one is more stable depending on the chemical modification made on the monoterpene ring close to the pivot bond. Extended analysis of TS structures to previously reported phenyl derivatives bearing the same O-substituent led to similar rotational pathways according to the series: through TS1 in arylcylohexenes and TS2 in arylcyclohexanes. Likewise, conversion of arylcyclohexenes into both series affects the rotation speed by decelerating it, and the nature of the aryl ring seems to have a very minor effect on this phenomenon.