{
  "abstract": "Enantioconvergent amidation of racemic alcohols offers a powerful retrosynthetic disconnection to convert abundant, readily accessible alcohol feedstocks into chiral N-alkyl amides, while streamlining access to valuable enantioenriched primary amines. However, a mechanistic framework that can integrate efficient C(sp3)–O bond cleavage with enantioselective amidation has remained understudied. Herein, we report the enantioconvergent deoxygenative amidation of racemic alcohols through a Cu-catalyzed radical relay. β-Scission of oxidant-derived electrophilic alkoxy radicals was leveraged as a radical-umpolung event, producing nucleophilic methyl radicals that effectively activate alcohol substrate-derived xanthates. Computation-guided optimization revealed that increasing xanthate electrophilicity facilitates methyl-radical addition and improves reaction efficiency. The transformation accommodates a variety of alcohols and amides with high enantioselectivity, and the reaction conditions are compatible with medicinally relevant functional groups, heterocycles, and pharmaceutical frameworks. Synthetic applications of this protocol streamline access to enantioenriched β-amino alcohols and biologically active primary amines, circumventing the need for enantioenriched alcohol precursors. Mechanistic studies revealed that polarity matching favors the capture of electron-deficient carbon-centered radicals by electron-rich CuII–amidates. Under catalytic conditions, however, the greater acidity of electron-deficient amides facilitates transmetalation, accelerating the formation of CuII–amidate and enhancing coupling efficiency.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Jonathan Vu"
    },
    {
      "name": "Eve Yuanwei Xu"
    },
    {
      "name": "Tanner S. Schubert"
    },
    {
      "name": "Matthew J. Metzger"
    },
    {
      "name": "Yongxian Li"
    },
    {
      "name": "Robert S. Paton"
    },
    {
      "name": "Yuyang Dong",
      "orcid": "0000-0002-4533-4798"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3yz14v04baarq.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010339/v1",
  "fulltext_url": null,
  "id": "3yz14v04baarq",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010339/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": "W7221710286",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/3yz14v04baarq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010339",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010339/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Asymmetric Synthesis and Catalysis",
      "subfield": "organic"
    }
  ],
  "title": "Cu-Catalyzed Enantioconvergent Synthesis of N-Alkyl Amides from Racemic Alcohols",
  "title_text": "Cu-Catalyzed Enantioconvergent Synthesis of N-Alkyl Amides from Racemic Alcohols",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/3yz14v04baarq",
  "venue": "ChemRxiv",
  "versions": []
}