Stable and responsive atropisomerism around a carbon–iodine bond

Abstract

Atropisomerism, a unique form of chirality arising from restricted bond rotation, enriches molecular diversity and plays a pivotal role in drug discovery, catalysis, and materials science. Although atropisomers with chiral axes based on second-row elements (e.g., biaryls) are common, stable atropisomerism around a long, flexible axis involving heavier elements remains rare. Here, we introduce stable atropisomers featuring a carbon–iodine bond as a sole chiral axis, achieved through pairing a rigid benziodoxole scaffold with a bulky fused aryl group. These molecules exhibit thermally robust atropisomerism, with rotational barriers over 30 kcal mol–1 and racemization half-lives surpassing 50 years. Notably, these C–I atropisomers exhibit acid-responsive racemization rates that vary with acidity, enabling semi-static or dynamic atropisomerism. This feature enables the use of 19F NMR to characterize their enantioselective interactions with weak chiral acids and their deracemization mediated by strong chiral acids.

Publication
Abe, S.; Kikuchi, J.; Matsumoto, A.; Yoshikai, N. Chem DOI:10.1016/j.chempr.2025.102527