{
  "abstract": "The catalytic enantioselective synthesis of inherently chiral macrocycles remains a major challenge, particularly through non-cyclization strategies. Herein, we report a chiral phosphoric acid (CPA)-catalyzed remote desymmetrization of tetraoxacalix[2]arene[2]triazines, enabling access to inherently chiral heteracalix[4]aromatics. The strategy relies on sequential SNAr aminations, in which the first amination installs an aniline N–H unit as a “control handle” that both creates a hydrogen-bonding recognition site for the catalyst and suppresses macrocyclic ring inversion. In the subsequent CPA-catalyzed step, the monoaminated intermediate undergoes kinetic resolution, allowing asymmetric differentiation of two remote enantiotopic sites within a flexible macrocyclic scaffold. The method affords a broad range of inherently chiral heteracalix[4]aromatics in good yields and high to excellent enantioselectivities (up to 99% ee), and is further applicable to disubstituted products and diverse derivatizations. Mechanistic studies indicate that hydrogen-bond-assisted catalyst recognition and steric inhibition of conformational inversion are both crucial for enantiocontrol. This work establishes a practical asymmetric strategy for inherently chiral macrocycles and expands the scope of remote desymmetrization in flexible supramolecular scaffolds.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University Guangzhou 510006 China",
    "School of Pharmacy, Shenzhen University Medical School, Shenzhen University Shenzhen 518055 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhanpeng Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinjie Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyi Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanxing Kuang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhen Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Guofeng Li",
      "orcid": "0000-0002-7528-2036"
    },
    {
      "affs": [
        1
      ],
      "name": "Ming Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Liang Hong",
      "orcid": "0000-0002-3489-0633"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dydasj6gg3q7e.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc03931f",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13575756/",
  "id": "dydasj6gg3q7e",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://doi.org/10.1039/d6sc03931f",
  "language": "en",
  "licence": "CC-BY-3.0",
  "licence_label": "CC BY 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1605|Supramolecular Chemistry and Complexes"
    ]
  ],
  "openalex": "W7212005032",
  "pdf_url": "https://pubs.rsc.org/sc/article-pdf/doi/10.1039/D6SC03931F/13771905/d6sc03931f.pdf",
  "pmcid": "PMC13575756",
  "pmid": "42746267",
  "published": "2026-09-09",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/dydasj6gg3q7e.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:29Z",
      "native_id": "PMC13575756",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc03931f"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Supramolecular Chemistry and Complexes",
      "subfield": "organic"
    }
  ],
  "title": "Remote desymmetrization of tetraoxacalix[2]arene[2]triazines enables the asymmetric synthesis of inherently chiral heteracalix[4]aromatics",
  "title_text": "Remote desymmetrization of tetraoxacalix[2]arene[2]triazines enables the asymmetric synthesis of inherently chiral heteracalix[4]aromatics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:20:58Z",
  "url": "https://research.draconitic.com/paper/dydasj6gg3q7e",
  "venue": "Chemical Science",
  "versions": []
}