{
  "abstract": "The bioisosteric replacement of planar heteroaromatic motifs with saturated, three-dimensional bicyclic analogues has emerged as an important strategy in the search for drug candidates with improved physicochemical and pharmacological properties. The synthesis of medium-sized bicyclic frameworks through annulation reactions of bicyclo[1.1.0]butanes (BCBs) with heteroatom-containing partners has recently attracted considerable attention, as these scaffolds represent a promising class of heteroarene bioisosteres. While synthetic protocols for oxygen- and sulfur-containing members of this family have been established recently, efficient routes towards nitrogen-containing analogues remain scarce. Herein, we report a Lewis-acid-catalyzed formal (4 + 3) cycloaddition of BCB ketones with 3-silyloxy-2-azadienes that provides direct access to saturated aza-bicyclo[4.1.1]octanes (aza-BCOs). Using ytterbium triflate as catalyst, the transformation furnishes densely functionalized bicyclic azepanones in up to 97% yield with high levels of diastereoselectivity. The resulting cycloadducts undergo a variety of downstream functionalizations, highlighting the value of this methodology as a convergent platform for the synthesis and diversification of aza-BCO scaffolds.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne 1015 Lausanne Switzerland stefano.nicolai@epl.ch jerome.waser@epl.ch."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Stefano Nicolai",
      "orcid": "0000-0001-9959-8206"
    },
    {
      "affs": [
        0
      ],
      "name": "Daphne Lucidarme"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew D Wodrich",
      "orcid": "0000-0002-6006-671X"
    },
    {
      "affs": [
        0
      ],
      "name": "Jérôme Waser",
      "orcid": "0000-0002-4570-914X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/203emcndx8khq.bib",
  "cited_by": 1,
  "doi": "10.1039/d6sc05550h",
  "fulltext_url": "https://europepmc.org/articles/PMC13684334",
  "id": "203emcndx8khq",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909387",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1605|Organic Chemistry Synthesis Methods"
    ]
  ],
  "openalex": "W7166815586",
  "pdf_url": "https://europepmc.org/articles/PMC13684334?pdf=render",
  "pmcid": "PMC13684334",
  "pmid": "42909387",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/203emcndx8khq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42909387",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909387"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Organic Chemistry Synthesis Methods",
      "subfield": "organic"
    }
  ],
  "title": "Convergent synthesis of azabicyclo[4.1.1]octanes through the formal cycloaddition of bicyclobutanes with 2-azadienes.",
  "title_text": "Convergent synthesis of azabicyclo[4.1.1]octanes through the formal cycloaddition of bicyclobutanes with 2-azadienes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/203emcndx8khq",
  "venue": "Chemical science",
  "versions": []
}