The optimized conditions for continuous-flow palladium-catalyzed C–N bond-forming reactions have been determined. They require the use of aqueous KOH, toluene as the solvent, tetrabutylammonium bromide as a phase-transfer catalyst, and a packed-bed microreactor (see scheme; TBAB=tetrabutylammonium bromide). In some cases, peforming these reactions under harsh conditions led to greatly enhanced reaction rates.
“Packed-bed reactors for continuous-flow C-N cross-coupling”, Angew. Chem. Int. Ed., 2010, 49(49), 9469-9474.