Green Chemistry Approaches in Aqueous Organic Synthesis

The adoption of water as a primary reaction medium has revolutionised sustainable organic synthesis by eliminating or drastically reducing the need for traditional organic solvents. Both “in-water” and “on-water” protocols exploit unique hydrogen-bonding networks and interfacial effects to accelerate reactions, enhance selectivity and access novel reactivity. Designer surfactants and micellar assemblies create nanometre-scale reaction vessels that solubilise hydrophobic reagents and enable ppm-level metal and biocatalysis under mild conditions. Photoredox strategies harness visible light in aqueous environments to drive radical and cycloaddition processes, while confined water cages amplify stereochemical control. These developments deliver lower E-factors, reduced hazard profiles and simplified work-up procedures. The global impact spans pharmaceutical manufacturing, agrochemicals and advanced materials, underscoring water’s role as both a green solvent and a mediator of unconventional reactivity pathways.

Research from Nature Portfolio

Recent studies have demonstrated an on-water accelerated dearomative [2+2] cycloaddition via aquaphotocatalysis to construct heterocyclic sulfonyl fluoride hubs, with water–oil interfaces amplifying reactivity under visible-light irradiation. Another investigation has revealed that confining reactants within nanoscale water cages markedly amplifies enantioselectivity through hydrophobic hydration effects, with droplet size dictating transition-state organisation. Foundational work on Kumada–Grignard-type biaryl couplings in pure water has further shown that in situ formation of Grignard species, promoted by magnesium and palladium catalysts, can yield symmetrical and unsymmetrical biaryls without organic solvents, challenging traditional ether-based protocols.

Green Chemistry Approaches in Aqueous Organic Synthesis publication trend

The graph below shows the total number of articles in green chemistry approaches in aqueous organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Surfactant: Amphiphilic molecule that self-assembles into micelles to solubilise hydrophobic reagents in water.

Micellar catalysis: Catalytic transformations occurring within surfactant-derived nanometre-scale reaction compartments in aqueous media.

Aquaphotocatalysis: Photocatalytic activation of substrates at the water–organic interface under visible light.

SuFEx: Sulfur(VI) fluoride exchange, a click-style reaction forming robust sulfonyl fluoride bonds.

On-water acceleration: Rate enhancement observed when insoluble reactants are processed at the water interface.

Chirality amplification: Enhancement of enantioselectivity resulting from confined aqueous environments that organise transition states.

References

1. “On-Water” accelerated dearomative cycloaddition via aquaphotocatalysis. Nature Communications (2024).
2. Introducing Savie: A Biodegradable Surfactant Enabling Chemo- and Biocatalysis and Related Reactions in Recyclable Water. Journal of the American Chemical Society (2023).
3. Simplified Preparation of ppm Pd-Containing Nanoparticles as Catalysts for Chemistry in Water. ACS Catalysis (2023).
4. Water as the reaction medium in organic chemistry: from our worst enemy to our best friend. Chemical Science (2021).
5. Visible-Light Photoredox Catalysis in Water. The Journal of Organic Chemistry (2022).
6. Hydrophobic chirality amplification in confined water cages. Nature Communications (2019).
7. Kumada–Grignard-type biaryl couplings on water. Nature Communications (2015).