Improved Substrate Scope in the Potassium Hexacyanoferrate(II)-Based Cyanation for the Synthesis of Benzonitriles and Their Heterocyclic Analogues

Jeffery Richardson, Simon P. Mutton

Index: 10.1021/acs.joc.8b00515

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Abstract

The use of Pd(DPEPhos)Cl2 (P26) as a catalyst for the formation of benzonitriles and their heterocyclic analogues provides excellent complementarity to existing catalysts, allowing highly electron-deficient heterocyclic aryl halides to be efficiently converted to the corresponding nitriles using K4[Fe(CN)6]) as cyanide source. This catalyst significantly enhances the scope of this reaction to include a number of substrates that are highly relevant for pharmaceutical and agrochemical applications. Importantly, not only does this cyanation method employ a nontoxic cyanide source, simple semiquantitative testing suggests that, unlike many other methods, no free cyanide is present in the reaction mixture or during a variety of potential workups, thus improving the safety aspects of this method from initial setup through to product isolation. Finally, developing and testing a series of convenient cyanation kits has allowed facile application and broader adoption of this method in our laboratories.