{
  "abstract": "A major challenge in late-stage functionalization is the selective N-arylation of unsymmetric pyrazoles, five-membered heterocycles with two adjacent nitrogen atoms, which are prevalent in blockbuster medicines and bioactive molecules. Traditional cross-coupling methods usually favour one type of regioisomer, limiting access to complementary structures that could accelerate drug discovery and streamline structure-activity relationship studies. Here we show that copper catalysis harnesses arynes to achieve switchable arylation of pyrazoles under mild conditions. By tuning Cu-pyrazole coordination, we direct arylation to either nitrogen atom, unlocking selectivity between two similar sites. Mechanistic studies reveal how steric and electronic effects govern regioselectivity, transforming an inherently unpredictable process into a blueprint for selective recognition of N-N linkages. This approach establishes a general strategy for controlling site selectivity in nitrogen-rich heterocycles and highlights the use of strained intermediates in late-stage diversification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of California, Irvine, Irvine, CA, USA",
    "Department of Chemistry, Binghamton University, Binghamton, NY, USA",
    "Department of Chemistry, Binghamton University, Binghamton, NY, USA. jhirschi@binghamton.edu",
    "Department of Chemistry, University of California, Irvine, Irvine, CA, USA. dongv@uci.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Minghao Wang",
      "orcid": "0009-0001-2171-3873"
    },
    {
      "affs": [
        0
      ],
      "name": "Xintong Hou",
      "orcid": "0009-0003-1945-6673"
    },
    {
      "affs": [
        1
      ],
      "name": "Stephanie A. Corio",
      "orcid": "0000-0001-9029-3895"
    },
    {
      "affs": [
        0
      ],
      "name": "Lori Digal"
    },
    {
      "affs": [
        2
      ],
      "name": "Jennifer S. Hirschi",
      "orcid": "0000-0002-3470-0561"
    },
    {
      "affs": [
        3
      ],
      "name": "Vy M. Dong",
      "orcid": "0000-0002-8099-1048"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5r2bwa6ryqzjg.bib",
  "cited_by": 7,
  "doi": "10.1038/s41557-026-02148-z",
  "fulltext_url": null,
  "id": "5r2bwa6ryqzjg",
  "issns": [
    "1755-4330",
    "1755-4349"
  ],
  "landing_url": "https://doi.org/10.1038/s41557-026-02148-z",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1605|Catalytic C–H Functionalization Methods"
    ]
  ],
  "openalex": "W7164554870",
  "pdf_url": "https://www.nature.com/articles/s41557-026-02148-z.pdf",
  "pmcid": "PMC11998777",
  "pmid": "40235503",
  "published": "2026-06-12",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5r2bwa6ryqzjg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:44Z",
      "native_id": "W7164554870",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41557-026-02148-z"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Catalytic C–H Functionalization Methods",
      "subfield": "organic"
    }
  ],
  "title": "Copper-catalysed site-selective arylation of pyrazoles",
  "title_text": "Copper-catalysed site-selective arylation of pyrazoles",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:03Z",
  "url": "https://research.draconitic.com/paper/5r2bwa6ryqzjg",
  "venue": "Nature Chemistry",
  "versions": []
}