Parallel mechanochemical optimization - Buchwald-Hartwig C-N coupling as a test case

Buchwald-Hartwig aromatic amination has been chosen as a test case for reaction condition optimization in a mechanochemical setting. A parallel approach has allowed a fast investigation of different parameters. In particular, liquid-assisted grinding (LAG) as well as addition of a grinding auxiliary (AG) proved to significantly increase the yield. Key learnings are the high reproducibility and the reliability of the NMR-yield as a surrogate for the isolated yield. Moreover the catalytic system (Pd(OAc)(2) in combination with tBuXPhosPdG3) compares favorably to previously published catalytic systems.