Mechanochemical synthesis of organosodium compounds through direct sodiation of organic halides
Organometallic reagents are essential in organic synthesis, with organolithium compounds being most widely used. However, as lithium becomes less abundant and increasingly expensive, organosodium compounds have emerged as promising alternatives, but their use in organic synthesis is limited by their poor solubility in organic solvents, the need for pre-activated sodium sources and the necessity for highly anhydrous conditions. Here we report a mechanochemical protocol for the direct generation of organosodium compounds from cheap and shelf-stable sodium lumps and readily available organic halides under bulk, solvent-free conditions. These reactions generate an array of organosodium compounds in minutes, without special precautions against moisture or temperature control. These nucleophiles can be used directly for one-pot nucleophilic addition reactions with electrophiles and nickel-catalysed cross-coupling reactions. Furthermore, this mechanochemical approach enables the sodiation of inert C–F bonds in organic fluorides. This method is anticipated to drive progress in sodium-based synthetic chemistry. A mechanochemical protocol for the direct synthesis of organosodium compounds is developed using cheap and shelf-stable sodium lumps and readily available organic halides under bulk, solvent-free conditions. This approach allows for the generation of an array of organosodium compounds in minutes, without special precautions against moisture or temperature control.
Authors
- Michelle Lowe (ORCID: https://orcid.org/0000-0001-9649-4938)
- Hajime Ito (ORCID: https://orcid.org/0000-0003-3852-6721)
- Roly J. Armstrong (ORCID: https://orcid.org/0000-0002-3759-061X)
- Keisuke Kondo
- Koji Kubota (ORCID: https://orcid.org/0000-0003-1522-291X)
- Nathan Davison (ORCID: https://orcid.org/0009-0006-7315-650X)
- Erli Lu (ORCID: https://orcid.org/0000-0002-0619-5967)
- Paul Gordon Waddell (ORCID: https://orcid.org/0000-0002-7851-7347)
Institutions
- Hokkaido University (JP)
- University of Birmingham (GB)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Synthesis
- Published
- 2025-12-08
- DOI
- https://doi.org/10.1038/s44160-025-00949-7
- Primary Topic
- Crystallography and molecular interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leverhulme Trust
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology