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 (Δ 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 (Δ 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.