Atropisomerism in Tertiary Biaryl 2-Amides: A Study of Ar-CO and Ar-Ar? Rotational Barriers

Abstract

A rotational barrier study was performed on eight tertiary biaryl 2-amides using variable temperature (VT) NMR and exchange (EXSY) spectroscopy experiments. Seven out of the eight 2-amido-2′-methylbiphenyls with additional 3- and 6-substitution patterns (1-7) were found to have approximately similar rotational barriers (G‡ Tc= 56.5 – 67.5 kJ/mol). However, for both 3- and 6-substitution (8), the rotational barrier was found to be significantly higher (G‡ = 102.6-103.8 kJ/mol). Computational studies performed on all eight compounds gave results in good agreement with the experimental rotational barriers. A transition state in which atropisomerism occurs by a cooperative rotation of the Ar-CO and Ar-Ar′ bonds depending on substituent location is proposed.