Synthesizing Aromatic Nitriles via Cyanation

Cyanation of aromatic/heteroaromatic halides/pseudohalides is still not always a straightforward transformation, especially if the reaction needs to be scaled up.

2 Ar-X  +  Zn(CN)2  ®  2 ArCN  +  ZnX2

Workers at BMS have recently published a paper where they describe an improved protocol for this transformation1.

They found that Pd2(dba)3 with XantPhos, Zn(CN)2 and i-Pr2NEt in DMAc at 85°C worked well, but their preference for was for a well-defined Pd(II) catalyst to make handling easier.  Using commercially available XantPhos-PdCl2 and Zn(CN)2 in DMAc at 85°C did not work unless 2 equivalents of i-Pr2NEt (relative to the amount of catalyst) were added.

The paper includes 14 examples using aromatic bromides with yields 51-96%.  The yield with bromostyrene was only 39% mainly due to polymerisation of the starting material.  There are 7 examples using heteroaromatic bromides with yields 63-93%.

  1. J.R. Coombs, K.J. Fraunhoffer, E.M. Simmons, J.M. Stevens, S.R. Wisniewski, and M. Yu, J. Org. Chem., 2017, 82, 7040-7044.