Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Inorganic Chemistry Laboratory, University of Oxford, Oxford, UK.
Nat Chem. 2023 Mar;15(3):357-365. doi: 10.1038/s41557-022-01095-9. Epub 2022 Dec 12.
Heterobiaryl compounds that exhibit axial chirality are of increasing value and interest across several fields, but direct oxidative methods for their enantioselective synthesis remain 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 an indole radical is generated in the reaction but that this is probably an off-cycle event, and that the reaction proceeds through formation of a chiral Fe-bound naphthoxy radical that is trapped by a nucleophilic indole. We envision that this simple, cheap and sustainable catalytic manifold will facilitate access to a range of heterobiaryl compounds and enable their application across the fields of materials science, medicinal chemistry and catalysis.
具有轴手性的杂芳基化合物在多个领域都具有越来越高的价值和重要性，但它们的对映选择性合成的直接氧化方法仍然难以捉摸。在这里，我们揭示了在铁催化剂存在下，使用手性 PyBOX 配体和氧化剂，可以实现萘酚和吲哚之间的直接偶联，以高产率得到具有高对映选择性的轴手性杂芳基化合物。该反应表现出显著的化学选择性，并且仅生成交叉偶联产物，而没有竞争性的同偶联产物。机理研究使我们能够假设在反应中生成了吲哚自由基，但这可能是一个非循环事件，反应通过形成手性 Fe 键合的萘氧基自由基进行，该自由基被亲核吲哚捕获。我们设想，这种简单、廉价和可持续的催化模式将有助于获得一系列杂芳基化合物，并使其能够在材料科学、药物化学和催化等领域得到应用。
