{
  "abstract": "While N–N atropisomeric N-aminoindoles are prevalent in natural products and bioactive molecules, the origin of reactivity and enantioselectivity in their isothiourea-catalyzed synthesis remains unclear. Herein, density functional theory (DFT) calculations are performed to investigate the mechanism of the isothiourea-catalyzed asymmetric synthesis of N–N atropisomeric N-aminoindoles. Our computational results demonstrate that the catalyst-free pathway proceeds via a high-energy barrier (30.0 kcal/mol) with negligible enantioselectivity. In the presence of the chiral isothiourea catalyst, the calculated energy difference between the two diastereomeric transition states is 4.7 kcal/mol, rationalizing the experimentally observed high enantioselectivity (>99:1 er). Both π–π stacking and nO → σ*S–C delocalization contribute to the stabilization of the rate-determining transition state. Meanwhile, energy decomposition and distortion/interaction analyses reveal that enhanced orbital overlap in the stereoselectivity-determining step governs enantioselectivity. Selenium substitution further lowers the rate-determining barrier from 18.0 to 15.1 kcal/mol without compromising enantioselectivity. In contrast, the NHC catalyst leads to poor chiral discrimination, with an energy difference of only 0.4 kcal/mol, consistent with the experimentally observed 50:50 product ratio. This work elucidates the mechanism of the isothiourea-catalyzed atroposelective synthesis and serves as a guide for the rational design of improved catalysts.",
  "abstract_shown": true,
  "affiliations": [
    "Shanxi Agricultural University , , ,",
    "Shandong University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingjing Li",
      "orcid": "0000-0003-0290-310X"
    },
    {
      "affs": [
        0
      ],
      "name": "Meichen Feng"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongju Zhang",
      "orcid": "0000-0002-6117-4958"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fk9skqz92mqev.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.6c09961",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737985/",
  "id": "fk9skqz92mqev",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c09961/5454100/DFT-Study-on-Reactivity-and-Enantioselectivity-in",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1605|Axial and Atropisomeric Chirality Synthesis"
    ]
  ],
  "openalex": "W7223062010",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c09961",
  "pmcid": "PMC13737985",
  "pmid": "42992069",
  "published": "2026-10-20",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/fk9skqz92mqev.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.6c09961",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c09961/5454100/DFT-Study-on-Reactivity-and-Enantioselectivity-in"
    },
    {
      "first_seen": "2026-11-09T12:23:04Z",
      "native_id": "PMC13737985",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acsomega.6c09961"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Axial and Atropisomeric Chirality Synthesis",
      "subfield": "organic"
    }
  ],
  "title": "DFT Study on Reactivity and Enantioselectivity in Isothiourea-Catalyzed Synthesis of N–N Atropisomeric N-Aminoindoles",
  "title_text": "DFT Study on Reactivity and Enantioselectivity in Isothiourea-Catalyzed Synthesis of N–N Atropisomeric N-Aminoindoles",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:04Z",
  "url": "https://research.draconitic.com/paper/fk9skqz92mqev",
  "venue": "ACS Omega",
  "versions": []
}