Determination of the Atropisomeric Stability and Solution Conformation of Asymmetrically Substituted Biphenyls by Means of Vibrational Circular Dichroism (VCD)

Vibrational-circular-dichroism (VCD) studies of the solution conformations of three 2,2′-substituted biphenyls are reported. Biphenyls with only two substituents at the peri-position normally show rotation about their central axis of chirality at room temperature in solution. We previously found no evidence for rotation of (P,4S)-2-[4,5-dihydro-4-(1-methylethyl)oxazol-2-yl]-2′-(hydroxymethyl)-1,1′-biphenyl (1) in CDCl3 about its 1,1′- axis, due to stabilization by intramolecular H-bonding and the presence of the i-Pr substituent, but two conformers were found in solution that result from rotation of the heterocycle in 1 between OH⋅⋅⋅N (the form present in the solid state) and the OH⋅⋅⋅O H-bonded forms, with no rotation of the i-Pr group or (P)  (M) twist [1]. For (P,S)-2, where the i-Pr substituent of 1 has been replaced by a Ph group, rotation of the heterocycle takes place in CDCl3 solution. For (P,S)-3 and (M,S)-4, where Me substitution at the two 6,6′-positions of (P,S)-1 prevents rotation about the central axis of chirality, rotation of the heterocycle is observed for the (P)-configuration ((P,S)-3), but not for the (M)-configuration ((M,S)-4). Only one rotamer involving the i-Pr group, which was found in the solid state of (P,S)-3, was also observed in solution, but (M,S)-4, obtained as an oil, was found to be a mixture of three rotamers of the i-Pr group.

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