Enantioselective synthesis of atropisomeric indoles via iron catalysed oxidative cross-coupling

Heterobiaryl compounds that exhibit axial chirality are of increasing value and interest across several fields, but direct oxidative methods for their enantioselective synthesis are elusive. Here we disclose that an iron catalyst in the presence of a chiral PyBOX ligand and an oxidant enables direct coupling between naphthols and indoles to yield atropisomeric heterobiaryl compounds with high levels of enantioselectivity. The reaction exhibits remarkable chemoselectivity and exclusively yields cross-coupled products without competing homocoupling. Mechanistic investigations enable us to postulate that the reaction proceeds through selective formation of an indole radical which is trapped by a chiral iron naphthoate in a radical–anion type coupling process. We envision that this simple, cheap, and sustainable catalytic manifold will facilitate access to a range of heterobiaryl compounds and enable their applications across the fields of materials science, medicinal chemistry, and catalysis.