Atropisomers

Atropisomerism is a form of stereoisomerism arising from hindered rotation about a single bond, most commonly the aryl–aryl bond in biaryl systems. When the barrier to rotation is sufficiently high, the molecule exists as two non-superimposable, stable conformers that are related by rotation around that bond and cannot readily interconvert at a given temperature. Each of these conformers can be enantiomeric or diastereomeric, depending on the symmetry and substituents of the molecule.

Axial chirality underpins atropisomerism. The stereochemical character is often described as axial (R_a or S_a) rather than center-based. If the barrier to rotation is low, rapid interconversion occurs and no resolvable atropisomers remain at ambient conditions; such systems are considered dynamically atropisomeric. At higher barriers, the two axes give rise to isolable atropisomers that can be separated and individually characterized, effectively behaving as distinct enantiomers or diastereomers.

Molecular features that promote atropisomerism include bulky substituents at ortho positions of the aryl rings, which create steric hindrance to rotation. The archetypal case is 2,2'-disubstituted biaryls, though heterobiaryls and other rigid frameworks can exhibit axial chirality as well. Examples appear in various natural products and synthetic ligands.

Applications of atropisomerism span chemistry and pharmacology. Axially chiral ligands, such as BINAP and related systems, are important in asymmetric catalysis. Atropisomeric drug candidates and natural products demonstrate how axis chirality can influence biological activity. Analytical methods for atropisomers include chiral chromatography, NMR with resolvable signals, and X‑ray crystallography to determine absolute configuration.