{
  "abstract": "In this work, we present a computational study that provides evidence for the origins of selectivity in the enantioselective synthesis of pyrroloindolines catalyzed by iminium ions. Through a conformational search combined with DFT calculations, we obtained the catalytic energy profile, which shows that the enantioselectivity is not determined by the barriers of the enantiodetermining C–C bond-forming step. A microkinetic model built on this profile reproduces the experimental enantiomeric excess and identifies the origin of the selectivity: under conditions in which the steps preceding product release are reversible, the catalyst-bound intermediate I9 accumulates preferentially along the S pathway, where it is markedly more stable than its R counterpart. The selectivity therefore reflects a thermodynamic contribution operating at the level of the diastereomeric on-cycle intermediates rather than a difference in activation barriers. We stress that this outcome is not accessible from the free energy profile alone: a simple inspection of the activation barriers predicts the opposite sense of induction, and only the explicit kinetic treatment reproduces the experimental results. Previous studies have suggested that control of the E/Z ratio of the iminium ion intermediate was related to catalytic selectivity; here we show that the stereoinduction originates from the predominance of the E isomer of the iminium ion. Furthermore, for the C–C bond-forming step, we identify the regions of the system involved in the noncovalent interactions that govern selectivity. Finally, by introducing substituents on the substrate, we observe a decrease in the activation barrier associated with the iminium ion–substrate interaction when electron-donating groups are present in the nucleophile.",
  "abstract_shown": true,
  "affiliations": [
    "Departamento de Química Fundamental",
    "Instituto de Química, Universidade de São Paulo"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Felipe Schoma Cardoso"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bruno Matos Paz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ataualpa A. C. Braga",
      "orcid": "0000-0001-7392-3701"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aw89s079wtb44.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009131/v1",
  "fulltext_url": null,
  "id": "aw89s079wtb44",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009131/v1",
  "language": null,
  "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|Asymmetric Synthesis and Catalysis"
    ]
  ],
  "openalex": "W7213950846",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009131/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/aw89s079wtb44.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15009131",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009131/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Asymmetric Synthesis and Catalysis",
      "subfield": "organic"
    }
  ],
  "title": "When the lower-barrier pathway yields the minor enantiomer: reversibility and intermediate stability in pyrroloindoline synthesis",
  "title_text": "When the lower-barrier pathway yields the minor enantiomer: reversibility and intermediate stability in pyrroloindoline synthesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/aw89s079wtb44",
  "venue": "ChemRxiv",
  "versions": []
}