Catalytic transition metal species are essential tools for the assembly of bioactive molecules. The need for practical and economic translation of these laboratory methods to large-scale operations and the need for cleaner manufacturing processes has led to the development of new strategies for reagent immobilisation that can allow for the better recovery and reuse of catalysts.
In typical supported transition metal catalysts, the metal is coordinated to a ligand which is covalently bound to a polymer backbone, or it is adsorbed on an inert surface such as silica or carbon. Using this approach, synthesis of the polymer-bound ligand can be lengthy and expensive and there can be problems associated with leaching and the reactivity of the catalyst.
Microencapsulation, a process of entrapping materials in a polymeric coating, may offer a solution to these problematic limitations. Microcapsules can be prepared by an in situ interfacial polymerisation approach involving dispersing an organic phase containing polyfunctional monomers and/or oligomers (along with the material to be encapsulated) into an aqueous phase containing a mixture of emulsifiers and protective colloid stabilisers. This resulting oil-in-water emulsion undergoes in situ interfacial polymerisation, with the monomers/oligomers reacting spontaneously at the phase interface to form microcapsule walls. The permeability and size of these microcapsules and the coordinating properties of the polymer matrix may be tuned by varying the nature of monomers/oligomers, other reagents and conditions used in the encapsulation procedure. We found polyurea microcapsules to be suitable to ligate and thus retain metal species such as Pd(OAc)2  to create palladium(II) acetate microencapsulated in polyurea [PdEnCat‚Ñ¢].
Our first PdEnCat™ microcapsules were tested for catalytic activity in Suzuki-type reactions involving the cross-coupling of aryl boronic acids with aryl bromides. We found the reactions proceeded smoothly to give the required biaryl products in good yields .
These microcapsules also performed well in carbonylation reactions to prepare aryl esters from commercially available aryl iodides and Heck type couplings, both in conventional solvents and supercritical carbon dioxide (scCO2) .
A highly efficient heterogeneous palladium catalyst [Pd0EnCat] for transfer hydrogenation was prepared by treatment of [PdEnCat™] with HCOOH leading to deposition of Pd(0) in the polyurea support material . This catalyst has been proven to be highly efficient and chemoselective in the reduction of carbonyl and nitro groups. The stability of the catalyst has also been demonstrated convincingly by conducting five successive runs without an obvious drop in the reaction rate. Also see our series of catalytic hydrogenations reactions .
We have also shown that Pd nanoparticles (approx. 2 nm in size) microencapsulated in polyurea are an efficient and recyclable catalyst for reductive ring-opening hydrogenolysis of epoxides, using either HCOOH/Et3N or H2 as a hydrogen donor .
PdEnCat™ and tetra-n-butylammonium salts have also proved to be an efficient and economical catalytic system for Suzuki cross-coupling reactions  and we went on to develop new prototcols for conducting these reactions in flow using cooled microwave heating .
We have also developed protocols for microwave-assisted Sonogashira cross-coupling of aryl iodides and bromides with terminal alkynes using PdEnCat™ .
1. Encapsulation of palladium in polyurea microcapsules C. Ramarao, S.V. Ley, S.C. Smith, I.M. Shiley, N. DeAlmeida J. Chem. Soc., Chem. Commun. 2002, 1132-1133
2. Polyurea-encapsulated palladium(II) acetate: a robust and recyclable catalyst for use in conventional and supercritical media S.V. Ley, C. Ramarao, R.S. Gordon, A.B. Holmes, A.J. Morrison, I.F. McConvey, I.M. Shirley, S.C. Smith, M.D. Smith
J. Chem. Soc., Chem. Commun. 2002, 1134-1135
3. Transfer hydrogenation using recyclable polyurea-encapsulated palladium: efficient and chemoselective reduction of aryl ketones J-Q Yu, H-C. Wu, C. Ramarao, J.B. Spencer, S.V. Ley J. Chem. Soc., Chem. Commun. 2003, 678-679
4. Palladium acetate in polyurea microcapsules: a recoverable and reversible catalyst for hydrogenations N. Bremeyer, S.V. Ley, C. Ramarao, I.M. Shirley, S.C. Smith
Synlett, 2002, 1843-1844
5. Recyclable polyurea-microencapsulated Pd(0) nanoparticles: an efficient catalyst for the hydrogenolysis of epoxides C. Mitchell, D. Pears, S.V. Ley, J-Q. Yu, W. Zhou Org. Lett. 2003, 5, 4665.
6. Efficient batch and continuous flow suzuki cross-coupling reactions under mild conditions, catalysed by polyurea-encapsulated palladium(II) acetate and tetra-n-butylammonium salts C.K.Y. Lee, A.B. Holmes, S.V. Ley, I.F. McConvey, B. Al-Duri, G.A. Leeke, R.C.D. Santos, J.P.K. Seville J. Chem. Soc., Chem. Commum. 2005, 2175-2177
7. Microwave assisted suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous flow transformations I.R. Baxendale, C.M. Griffiths-Jones, S.V. Ley, G. Tranmer Chem. Eur. J. 2006, 12, 4407-4416
8. PdEnCat‚Ñ¢ TPP30 as a catalyst for the generation of highly functionalized aryl- and alkenyl-substituted acetylenes via microwave assisted Sonogashira type reactions J. Sedelmeier, S.V. Ley, H. Lange, I.R. Baxendale Eur. J. Org. Chem. 2009, 4412-4420