atropisomeric

Atropisomeric refers to a form of stereoisomerism where a molecule exists as two or more distinct stereoisomers due to restricted rotation about a single bond. The phenomenon is a type of axial chirality, arising when the barrier to rotation about a bond—most commonly the aryl–aryl bond in biaryl systems—is sufficiently high to prevent rapid interconversion at practical temperatures. When the barrier is large enough, the individual conformers become isolable atropisomers, each with a fixed spatial arrangement of its substituents around the axis.

The origin of atropisomerism lies in steric hindrance from bulky substituents, typically at the ortho positions of adjacent aryl rings. If rotation around the axis would bring substituents into clash, interconversion slows or stops, allowing stable atropisomers to exist. Conversely, with small substituents or less hindrance, the conformers interconvert rapidly and no separate atropisomers can be observed. The stability of atropisomers is often assessed by estimating the activation energy for racemization or by measuring interconversion rates through variable-temperature NMR or kinetic studies.

Nomenclature and descriptors commonly use axial chirality labels such as Ra/Sa or P/M, reflecting the sense of twist around the stereogenic axis. Examples include classic biaryl compounds like 2,2'-disubstituted biphenyls and chiral ligands such as BINOL and BINAP, which rely on atropisomeric axial chirality for their catalytic activity. Atropisomerism also appears in other rigid, hindered frameworks beyond biaryls, and plays a significant role in drug design, catalysis, and materials science.

Detection and characterization typically involve chiral separation methods (such as chiral HPLC), spectroscopic techniques (including circular dichroism), and structural determination by X-ray crystallography, complemented by kinetic or computational analyses to estimate rotational barriers.