Mechanochemical one-pot Barbier/Simmons–Smith reaction via sequential zinc activation

Asma A. Alharthi, Benson M. Kariuki, Louis C. Morrill, Duncan L. Browne

Research output: Contribution to journalArticlepeer-review

Abstract

We report a mechanochemical one-pot Barbier/Simmons–Smith reaction enabled by ball-milling-mediated activation of zinc(0). This operationally simple method generates organozinc intermediates in situ and uses them sequentially in allylation and cyclopropanation without intermediate work-up. The protocol tolerates a broad range of ketones, exhibits selectivity over other carbonyl groups, and is compatible with various physical forms of zinc metal. In selected cases, the reaction proceeds with markedly enhanced diastereoselectivity under minimal-solvent milling conditions and was demonstrated on a gram scale using standard ball-milling equipment. Comparative studies show advantages over conventional solution and neat conditions, highlighting how mechanochemistry can uniquely enable tandem organometallic processes as for C–C bond construction.

Original languageEnglish
JournalChemical Communications
Early online date23 Dec 2025
DOIs
Publication statusE-pub ahead of print - 23 Dec 2025

Data Availability Statement

The data supporting this article have been included as part of the supplementary information (SI). The data supporting the findings of this study, including raw NMR, IR, and mass spectrometry datasets are openly available from the Cardiff University data repository at https://doi.org/10.17035/cardiff.30287158. See DOI: https://doi.org/10.1039/d5cc05732a.

CCDC 2441709 contain the supplementary crystallographic data for this paper.

Acknowledgements

We gratefully acknowledge the School of Chemistry at Cardiff University, the Department of Chemistry at the University of Bath and the School of Pharmacy at University College London for generous support. We thank the Saudi Arabia cultural mission in the UK and the Department of Chemistry at the University of Jeddah (A.A.) for PhD studentship. We also thank Dr Matthew Tredwell for his supervision and support.

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Catalysis
  • Ceramics and Composites
  • General Chemistry
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Materials Chemistry

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