Stable and responsive atropisomerism around a carbon–iodine bond

Atropisomerism, a critical form of molecular chirality originating from restricted bond rotation, enhances molecular diversity and plays a fundamental role in drug discovery, enantioselective catalysis, and materials science. While atropisomers with chiral axes composed of second-row elements, especially bulky biaryls, are common, stable atropisomerism around a “heavy” axis involving third-row or heavier elements remains rare. Here, we expand the scope of atropisomerism to the carbon–iodine bond, introducing the first stable atropisomers around this exceptionally long, flexible axis. Through a molecular design combining a conformationally restricted benziodoxole (BX) scaffold with a bulky fused aryl (Rind) groups, we achieve rotational barriers around the aryl–iodine bond exceeding 30 kcal mol–1 and racemization half-lives surpassing 50 years at room temperature, establishing the C–I bond as a viable stereogenic element. Notably, these C–I atropisomers exhibit acid-responsive racemization rates that vary with acidity, enabling semi-static or dynamic atropisomerism. This feature allows these compounds to serve as 19F-labeled NMR probes for weak chiral acids and as substrates for deracemization mediated by strong chiral acids.