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

Institutions

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

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Mechanochemical synthesis of organosodium compounds through direct sodiation of organic halides

Michelle Lowe, Hajime Ito, Roly J. Armstrong, Keisuke Kondo et al.
Nature Synthesis
Crystallography and molecular interactions
article

Mechanochemical synthesis of organosodium compounds through direct sodiation of organic halides

Michelle Lowe, Hajime Ito, Roly J. Armstrong, Keisuke Kondo, Koji Kubota, Nathan Davison, Erli Lu, Paul Gordon Waddell
article en

Abstract

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.

Nature Synthesis
Hokkaido University (JP), University of Birmingham (GB), Newcastle University (GB)
Leverhulme Trust, Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science, Core Research for Evolutional Science and Technology
Openalex Percentile: Top 66%
Crystallography and molecular interactions
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.