atropisomeri

Atropisomerism is a form of stereoisomerism that arises when rotation about a single covalent bond is sufficiently hindered to generate isolable, non-superimposable forms. It most commonly occurs in biaryl systems, such as substituted biphenyls, where bulky ortho substituents create a barrier to rotation about the aryl–aryl bond. When the barrier is high enough at a given temperature, the molecule exists as two enantiomeric or diastereomeric atropisomers that cannot readily interconvert. If the barrier is low, rapid rotation prevents isolation of distinct atropisomers, and the system is dynamic.

Key factors shaping the barrier are steric hindrance near the axis, conjugation, and overall molecular rigidity. Bulky substituents at the ortho positions, ring strain, and rigid frameworks increase the rotational barrier. The barrier is quantified as the activation free energy ΔG‡ for bond rotation, and its magnitude depends on temperature. At room temperature, barriers typically above about 20–25 kcal/mol allow resolvable atropisomers, while barriers above roughly 30 kcal/mol give long-lived, stable atropisomers.

Axial chirality is the most common manifestation of atropisomerism; other forms include planar or helical chirality in certain polycyclic systems. Classic examples are 1,1'-bi-2-naphthyl and BINOL/BINAP-type ligands, where restricted rotation yields stable enantiomeric axes used in enantioselective catalysis. Atropisomerism is important in drug discovery and materials science because different atropisomers can have distinct biological activity, binding properties, and physical characteristics. Synthesis and resolution of atropisomers remain active areas of research, with applications in asymmetric synthesis, chiral recognition, and functionally rich stereochemistry.