Atropisomerism is a type of stereoisomerism that results from restricted rotation around a single bond, and is most frequently observed in biaryl compounds. It is often exploited in the construction of chiral ligands for asymmetric catalysis — such as the ligand BINAP — and is also found in nature, an example being the antibiotic natural product vancomycin. There are, however, few ways to prepare compounds of this type in a stereoselective fashion. Now, Scott Miller and co-workers from Yale University have reported1 a dynamic kinetic resolution of biaryl compounds using a stereoselective electrophilic bromination.

Dynamic kinetic resolution works by converting one enantiomer of a starting material to product much more quickly than the other. Simultaneously, the starting material is rapidly racemized. In the case of atropisomerism, racemization only requires rotation around a single bond, so with judicious choice of starting material this can occur thermally at relatively low temperature. Provided the rotational barrier for the product is higher — so that the product does not racemize under the same conditions — then a dynamic kinetic resolution is possible. Miller and co-workers identified just such a substrate in some 3-aryl-substituted phenols.

Bromination of these phenols was found to be catalysed by simple amides, and an asymmetric variant was soon identified using peptide-derived catalysts that Miller and colleagues have shown to be useful for a wide range of other transformations. The explanation of the observed reactivity given by Miller and co-workers should also assist in identifying other atropisomeric substrates that can be resolved in this fashion.