Are stable atropisomers possible for meta-meta’ linked biphenols?

Abstract This paper describes the synthesis, structure, conformation and configurational stability of novel 8-atom meta,meta’-linked biaryls, as models for controlling the ratio of atropisomers through remote central chirality. The synthesis of model compounds is described where the configuration of the linker is provided by reduced C4 and C6 sugars. Their properties have been examined by X-ray, NMR and ECD. Taken together, they provide information on the conformation of the linking chain in each case and indicate a barrier to atropisomerisation in the region of 55 KJ mol-1. For the diastereomeric C6 compounds, the preferred atropisomer is defined by the configuration of the backbone secondary methyl groups. Computational analysis confirms the direction of axial chirality from ECD spectra and offers a model for the distinction between the (R,R,R,R) and (S,R,R,S) C6-isomers.