Transmetallation by Halogen-Cyanide Metathesis in Water: Application to Cyanide Ion-Free Palladium Catalyzed Cyanation.

Aryl nitriles are important synthons in organic chemistry, yet conventional cyanation methods mostly generate free cyanide ions, creating acute safety hazards and wastewater contamination issues. We report a Pd-catalyzed cyanide ion-free cyanation of aryl halides featuring a transmetallation potentially via halogen-cyanide (CN-) metathesis using potassium ferrocyanide as a bound CN- reservoir. Mechanistic studies, CN--sensing strip tests, and IR spectroscopy confirm that no free CN⁻ is released at any stage, eliminating toxicity and downstream CN- liabilities. Stable AshPhos-Pd nanoparticles formed within HPMC enable efficient cyanation across diverse (hetero)aryl bromides and chlorides under mild conditions. This approach likely combines process safety and environmental compliance, offering a scalable solution for late-stage CN- installation without the risks associated with free cyanide.