Safer Cyanation

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Science  30 Aug 2013:
Vol. 341, Issue 6149, pp. 939
DOI: 10.1126/science.341.6149.939-b

Cyanide (typically in an alkali salt) is such a well-known poison that many people may not realize how central it is to the production of pharmaceuticals and fine chemicals more generally. Covalently bound to carbon, the CN group no longer manifests the same sort of toxic properties, but getting it there—particularly onto aromatic rings—can be a fraught process. This is not only on account of its danger in bulk quantities; another problem is its tendency to bind tightly to metal catalysts and deactivate them before the reaction is complete. Senecal et al. present a practical and highly versatile catalytic method for cyanation of aryl chloride and bromides. They combine a previously investigated, nontoxic cyanide source (potassium ferrocyanide) with a particular palladium precursor and phosphine ligand combination that manifests high activity and broad functional group tolerance in a dioxane/water mixture with acetate base. The reactions, which generally proceed within 1 hour at 100°C with <1% catalyst loading, show compatibility with OH and NH groups, esters, aldehydes (at lower temperature to suppress competing benzoin condensation), and sulfur and nitrogen heterocyclic frameworks.

Angew. Chem. Int. Ed. 52, 10.1002/anie.201304188 (2013).

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