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.