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Synthetic methodology

Aryl ortho methoxylation

Nature Chemistry volume 15, pages 1334–1335 (2023)Cite this article

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Aryl ethers are useful intermediates in organic synthesis and are found in countless biologically active compounds. Now, through palladium/norbornene cooperative catalysis and incorporation of a polarity-reversed N–O reagent as the O-electrophile, an efficient arene methoxylation approach has been successfully developed.

Methoxy-substituted arenes are important structural motifs in biologically active molecules and pharmaceuticals1. Diverse arene functionalization could be enabled by methoxy groups through electrophilic aromatic substitution as well as cross-coupling reactions2, both of which stem primarily from their strong electron-donating character. There are two major routes for preparation of aryl ethers. The first is the arene C–H oxidation strategy, which is mainly limited by the requirement of auxiliary directing groups to control site-selectivity and by the functional-group tolerance of the strong oxidants3. The second approach relies on nucleophilic aromatic substitutions or cross-couplings, but precisely prefunctionalized aryl electrophiles or organometallic reagents are stringently needed4.

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Fig. 1: Alkyl aryl ethers and their preparations.

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Authors and Affiliations

  1. Hefei National Research Center for Physical Sciences at the Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, China

    Kun Zhao & Zhenhua Gu

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  1. Kun Zhao
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  2. Zhenhua Gu
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Correspondence to Zhenhua Gu.

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The authors declare no competing interests.

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Zhao, K., Gu, Z. Aryl ortho methoxylation. Nat. Chem. 15, 1334–1335 (2023). https://doi.org/10.1038/s41557-023-01323-w

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