Modular synthesis of axially chiral styrenes via atroposelective iodonium-Claisen rearrangement

Axially chiral biaryls are prominent chiral scaffolds in asymmetric synthesis, yet their counterparts, axially chiral styrenes, have been relatively overlooked due to the lack of robust synthetic methods. Recent advancements have shed light on their synthesis, but achieving structurally diverse and tunable axially chiral styrenes remains challenging due to their inherently lower rotational barriers and the difficulty in controlling the E/Z geometry of alkene moieties. Here, we report a versatile modular approach for synthesizing axially chiral styrenes through an atroposelective iodonium-Claisen rearrangement. The method utilizes readily accessible aryl/heteroaryl iodanes and E/Z-mixtures of α,β-unsaturated 2-oxazolines and achieves precise control over both E-geometry and atropochirality. Computational studies reveal an intriguing chirality evolution from the initial C(sp3)–C(sp3) axis to the final C(sp2)–C(sp2) axis. The transformable oxazoline group and iodine atom in the products facilitate the synthesis of structurally versatile axially chiral styrenes and biaryls, establishing a platform for these valuable axially chiral sources.