Recent Advances in the Synthesis of Nitrile Compounds Utilizing K4[Fe(CN)6]: Mechanistic Studies and Applications
Yan Zhang, Fachao Yan, Yue Zhang, Qing Liu, Hui LiuAbstract
The pursuit of sustainable synthetic methodologies has propelled K4[Fe(CN)6] to the forefront as an environmentally benign cyanating reagent in modern organic synthesis. This review systematically evaluates recent advances (2004–2025) in K4[Fe(CN)6]‐mediated cyanation reactions, with particular emphasis on its mechanistic versatility and green chemistry advantages over conventional cyanide sources. We present a comprehensive analysis of its application across four key bond functionalizations: 1) C─X (X = halogen, pseudo‐halogen) bond cyanation, 2) C─C bond cleavage/cyanation strategies, 3) C─O bond activation in phenols aryl mesylates, and 4) direct C─H cyanation through transition metal‐catalyzed or transition metal free catalyzed pathways. Detailed comparisons of catalytic systems highlight structure–reactivity relationships, with quantitative evaluation of substrate scope, yield distributions for most systems, and selectivity profiles. Emerging applications in pharmaceutical intermediate synthesis and scalability underscore its industrial potential, positioning K4[Fe(CN)6] as a cornerstone reagent for sustainable nitrile synthesis in academic and industrial settings.