Dynamic Kinetic Resolution of Biaryl Atropisomers via Peptide-Catalyzed Asymmetric Bromination

Abstract

Selectively Spun Biaryl compounds, in which two phenyl rings are linked by a single bond, exhibit an interesting sort of chirality, termed atropisomerism. If bulky substituents block the mutual rotation of the rings about the linking bond, then two isomers can be isolated that differ only in the direction one ring has swiveled away from the plane of the other. This feature is useful in ligand design for asymmetric catalysis and also appears in a number of polycyclic natural products. However, selective synthesis of a single isomer is difficult. Gustafson et al. (p. 1251 ) now show that a simple tripeptide derivative acts as an efficient catalyst for this purpose, trapping a freely rotating precursor in one orientation through selective bromination; the large bromine substituents then inhibit further swiveling.