Carbon-Carbon Cross Coupling Reactions

Palladium Catalyzed Carbon-Carbon Cross Coupling Reactions in Thermomorphous Double Emulsions

Palladium catalyzed cross coupling reactions are very important methods for forming carbon – carbon bonds. This reaction has found applications in the preparation of a wide spectrum of organic chemicals, materials and natural products.[1] However, most of the reactions are performed in homogeneous systems and have some common disadvantages, such as difficulties in separation of the catalyst from the product and the recycling of the catalyst. These problems can be avoided by using heterogeneous reaction conditions, but the catalyst activity in these systems was found to be significantly lower.[2]

viktor1Micro multiple emulsions offer the possibility for such multiphase reactions inside a micro droplet. In this case, the double emulsion consists of an inner phase: perfluorcarbon fluid, in which the palladium catalyst with fluorinated aryl ligands was dissolved; and an outer phase: a solution of the educts in an organic solvent. The continuous phase consists simply of an alkaline aqueous solution. Each droplet represents a single chemical micro-reactor, and the residence time is therefore well defined by the flow of the droplet through the channel and not broadened by a laminar flow profile.

viktor2The use of unique properties of perfluorinated fluids in multiphase systems allows combination of the advantages of homogeneous and heterogeneous catalysis by a thermo-regulated phase transition (thermomorphous properties). At elevated temperatures, both immiscible liquids (catalyst- as well reactant containing solution) turn into a homogeneous phase, while by lowering the temperature a complete phase separation will occur. This phase transition is a repeatable reversible process.[3]


By heating-up, the dispersed phases (catalyst phase and the phase containing the mixture of rbromo-benzene and styrene) become homogeneous at a temperature above 149°C. The time-determining steps of the reaction, i.e. the oxidative addition, the insertion and the β-H-elimination, then take place in a viktor4homogeneous solution, while the last step of the catalytic cycle, the reductive elimination, takes place on the surface between the dispersed and the continuous phase. By cooling the system down, the homogeneous droplet separates into two droplets containing the catalyst and the product, respectively . With a residence time of 18 min and a reaction temperature above 150°C, 96% yield of the desired coupling product was achieved. The catalyst solution was reused several times without remarkable loss of activity.[4]



[1] (a) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) Beletskaya, I. P.; Cheprakov, A. V., Chem. Rev. 2000, 100, 3009.
[2] (a) Ramchandani, R. K.; Uphade, B. S.; Vinod, M. P.; Wakharkar, R. D.;
Choudhary, V. R. Sudalai, A., Chem. Commun. 1997, 2071. (b) Djakovitch, L.; Koehler, K, J. Am. Chem.
Soc. 2001, 123, 5990. (c) Molnar, A.; Papp, A.; Miklos, K.; Forgo, P., Chem. Commun. 2003, 2626.
(d) Proeckl, S. S.; Kleist, W.; Gruber, M. A.; Koehler, K., Angew. Chem., Int. Ed. 2004, 43, 1881.
[3] (a) I.T. Horvath, J.Rabai, Science, 1994, 266, 72-75; (b) Horvath, Kiss, Cook, Bond, Stevens, Rabai, J.Am.Chem.Soc. 1998,120, 3133-3143
[4] V.Misuk, A. Mai, D. Rauber, K. Giannopoulos, H. Löwe,; Proceedings of the "International Conference on Microreaction Technology IMRET13", pp. 44-53; (June 23 - 25, 2014); Budapest, Hungary.