Statistical experimental design-driven discovery of room-temperature conditions for palladium-catalyzed cyanation of aryl bromides

A combination of Pd2(dba)3·CHCl3 (0.5 mol %) and commercially available, air-stable phosphonium salt [(t-Bu)3PH]BF4 (1.4 mol %) in a presence of Zn powder and Zn(CN)2 as the cyanide source comprises an extremely efficient catalyst system for the cyanation of a diverse array of aryl bromides, at room temperature. This result emerged from an experimental strategy that combines the advantages of parallel, automated experimentation with the design of experiments (DOE) for the effective definition of an optimal set of reaction conditions.