Using water for chemical synthesis

Researchers from McGill University have discovered a way to use water as a solvent in one of the reactions most widely used to synthesise chemical products and pharmaceuticals.

Writing in the journal Nature Communications, Professor Chao-Jun Li and Dr Feng Zhou explained, “One of the most important methods for forming carbon-carbon bonds” - described by the researchers as “the essence of organic synthesis” - “is the Barbier-Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process.”

For the past two decades, researchers have been exploring ways to do away with chemists’ reliance on non-renewable petrochemical feedstocks and toxic solvents. One method has involved replacing the toxic solvents used in metal-mediated reactions with water - something that was considered impossible. And while researchers have succeeded in using water in metal-mediated reactions between carbonyl compounds and other halides, attempts to do so for the most challenging reaction, between aryl halides and carbonyl compounds, had never worked.

But the McGill researchers have discovered a catalytic system which, for the first time, allows direct metal-mediated reactions between aryl halides and carbonyl compounds in water. Professor Li and Dr Zhou found that rhodium - a metal primarily used in the catalytic converters of automobiles - as a catalyst together with zinc as a mediator can make the reaction possible in water.

The technique bypasses a number of challenges posed by conventional practices in carrying out the Barbier-Grignard reaction, according to the researchers, “such as strict exclusion of moisture and air, protection-deprotection of various acidic hydrogens in the substrates, and so forth. It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules and pharmaceuticals.”

The research marks a potential milestone in efforts to develop organic reactions in water.

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