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

22 June 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


oxidative cross-coupling

Supplementary materials

Supporting information
This file contains the synthetic methods for all compounds in the manuscript, along with data for all compounds (NMR, MS, X-ray, HPLC, ESR).

Supplementary weblinks


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