Recent progress in copper-free Sonogashira-Hagihara cross-couplings in water

The cross-coupling of terminal acetylenes for the construction of alkyne motives is a reaction type that is frequently required in the assembly of pharmaceuticals and natural products that use Sonogashira-Hagihara cross-coupling reactions. Although traditional procedures rely on the use of organic, usually hazardous, solvents with significant impact on the environment and humans, safer and more sustainable approaches have been developed in academia and industry during the last few years, and these rely on the use of water as green and non-hazardous reaction medium. This review first highlights the importance of Sonogashira-Hagihara couplings as well as micellar catalysis. Subsequently, the use of so-called benign-by-design surfactants in copper-free Sonogashira-Hagihara cross-couplings will be disclosed, before the focus is shifted to the use of other surfactants and co-solvents, as well as polymers. An outlook section proposes challenges and a potential future progress in this field.

Automated summary

The cross-coupling of terminal acetylenes is frequently required in pharmaceutical and natural product synthesis. Traditional methods using organic solvents have significant environmental and human health impacts. Safer and more sustainable approaches using water as a reaction medium have been developed.