Solvent-Free Buchwald–Hartwig Amination of Heteroaryl Chlorides by N-Heterocyclic Carbene–Palladium Complex (SIPr)Ph2Pd(cin)Cl at Room Temperature

Using the robust N-heterocyclic carbene-palladium complex (SIPr)^Ph2Pd(cin)Cl, a highly efficient and easy-to-operate method has been developed at room temperature for the solvent-free Buchwald-Hartwig amination of heteroaryl chlorides with various amines. The amount of catalyst can be as low as 0.05 wt %. The system was demonstrated on 47 substrates and successfully applied to the synthesis of commercial pharmaceuticals and candidate drugs with high yields. Furthermore, the protocol can be used to prepare aniline derivatives on a multigram scale without yield loss.