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%.
- 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.