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Mini-reviewReceived: 31 August 2011 Revised: 12 January 2012 Accepted: 13 January 2012 Published online in Wiley Online Library: 20 February 2012

(wileyonlinelibrary.com) DOI 10.1002/jctb.3748

Heterogeneously catalyzing C–C couplingreactions with precious metal nanoparticlesSimon K. Beaumont∗†

Abstract

C–C coupling reactions are ubiquitous in synthetic chemistry, joining together fragments of larger molecules within overallsynthetic schemes. Many obvious operational advantages would result from catalyzing such processes heterogeneously,however, there has been much controversy over whether metal nanoparticles (typically Pd) can be used in this role, or ifcatalysis in such cases occurs instead on metal ions leached into solution. In this mini-review selected examples of attemptsto distinguish the homo- or hetero-geneity of such reactions, using Pd and Au nanoparticles, are highlighted. In particular,several interesting recent results are explored that demonstrate such metal nanoparticle catalyzed reactions can occur in aheterogeneous mode.c© 2012 Society of Chemical Industry

Keywords: C–C coupling; heterogeneous; Heck; Suzuki; Sonogashira; mechanistic studies

INTRODUCTIONMetal-catalyzed coupling reactions that result in the formationof new C–C bonds are of paramount importance in syntheticorganic chemistry. This fact was recognized by the award of the2010 Nobel Prize for Chemistry to Heck, Negishi and Suzuki.1

Their reactions, along with other similar C–C couplings such asStille and Sonogashira, offer an extremely convenient route tojoin large fragments of molecules in a controlled manner – vitalfor designing convergent overall synthetic schemes. In additionto organic synthesis (an arena in which such reactions havebecome indispensible since the first homogeneous organometallicreagents appeared about 40 years ago)2 they have also begun tounlock new strategic approaches for the preparation of materialsfor use in optical and electronics applications.3 For example,they have been used in the production of functional stilbenesand bibenzyls for use in liquid crystals4 or the preparation ofconjugated oligomers that can be used in light emitting devices.5

In the production of fine chemicals and pharmaceuticals, theapplication of heterogeneous catalysts is especially attractivebecause of the considerable advantages offered by being ableto work in a continuous flow mode, also eliminating the needfor subsequent difficult steps to separate catalyst and products.Additionally, supported catalysts are increasingly adopted in theresearch laboratory, for example in microfluidic devices, for theautomated synthesis of chemical libraries.6

Heterogeneously catalyzing C–C coupling reactions, conven-tionally catalyzed by organometallic reagents, would be veryadvantageous and, as highlighted in a recent tutorial review,7

many reports now exist of nanoparticle catalyzed analogues ofthese reactions. However, mechanistic concerns remain and arethe focus of the present mini-review. These are seldom directlyinvestigated concerning whether catalysis takes place heteroge-neously on the surface of metal nanoparticles, or at single metalatoms leached into solution. Even when attempts have been madeto clarify this point, evidence has been presented in favour of bothmechanisms. Accordingly, the answer may very well depend on

the reaction and conditions used. The answer to the question ofwhether a heterogeneous reaction is actually possible is obviouslykey to any practical application. To be effective, the catalyst mustnot be leached away as either clusters or atoms, so as to preservethe lifetime of the catalyst and to prevent the often toxic leachedmetal species contaminating the product. Promisingly, two verydifferent systems have recently been reported to proceed over-whelmingly heterogeneously: oxide-supported gold nanoparticlecatalyzed Sonogashira coupling at high temperatures (145 ◦C),8,9

and unsupported palladium nanoparticle catalyzed Suzuki cou-pling at low temperatures (60 ◦C).10 Here, these systems and othersalient examples and evidence are explored concerning the homo-and hetero-geneity of nanoparticle catalyzed C–C coupling reac-tions. This mechanistic focus is adopted with a view to achievingthe goal of gaining understanding which will be technologicallyuseful in developing future heterogeneous catalysts.

CONVENTIONAL C–C COUPLING REACTIONSWhile earlier reports of reactions with harsh reagents such asorganolithium and Grignard reagents exist,11,12 the generallyaccepted landmark in the development of organometallic C–Ccoupling reactions was the publication by two independentresearchers on the palladium catalyzed coupling of aryl halideswith terminal olefins2,13 – the Heck reaction. As illustrated inFig. 1, after this point many C–C coupling reactions were

∗ Correspondence to: Simon K. Beaumont, Department of Chemistry, CambridgeUniversity, Lensfield Road, Cambridge, CB2 1EW, UK.E-mail: beaumont@berkeley.edu; simonb@cantab.net

† Current Address: Department of Chemistry, University of California, Berkeley,CA 94720 (USA).

Department of Chemistry, Cambridge University, Lensfield Road, Cambridge,CB2 1EW, UK

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Figure 1. Schematic showing the various key groups of C–C couplingreactions that have been discovered using aryl halides.

Figure 2. Typical catalytic cycle proposed for the homogeneous Heckreaction between aryl halides and olefins using a ligand-based Pd complex.

quickly developed, including the Sonogashira,14 Stille,15 andSuzuki–Miyaura16 couplings.

The typical catalysts for such systems are complexes ofpalladium with various ligands, though often supplied just asPd(acac)2 or Pd(PPh3)4. The palladium is then oxidized andreduced between Pd0 and PdII during the catalytic cycle.17 – 19

An example of such a catalytic cycle is given in Fig. 2, shownhere for a Heck coupling of an aryl halide and an olefin. Thereactions to couple aryl halides to other molecules are similar, withthe olefin binding step replaced by a transmetallation whereappropriate.‡ Despite the difficulty of separation, purificationand re-use of such homogeneous organometallic catalysts andthe need to carefully remove any residual palladium from thereaction product, there exist a number of patents based on thistechnology.21 One notable demonstration illustrated in Fig. 3 is theuse of Sonogashira coupling reactions in the synthesis of 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-ethylquinazoline, an antimitotic usedin cancer treatment.22 Although this example illustrates the use

‡ For the case of reaction with an alkyne (Sonogashira coupling), thehomogeneous catalyst often contains a copper co-catalyst homogeneouscatalyst, believed to facilitate acetylide formation;20 the reaction thenproceeds via a similar mechanism, again with a transmetallation step ratherthan direct insertion of Pd into the olefin.

Figure 3. Novartis synthesis of 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-ethylquinazoline (an antimitotic agent used in cancer treatment) usingSonogashira coupling steps to complete the synthetic scheme.

of such technology, it is still a batch process and the separationstages still form a considerable component of the cost. (Here, theproduct is separated from Pd by an unusual approach involvingcrystallization of the product while Pd is held in solution by abinding additive.)

HETEROGENEOUSLY CATALYZED C–CCOUPLINGThe many advantages of seeking to use truly heterogeneouscatalysts have already been discussed. Generally two commonapproaches exist to achieve this goal. One starts from ahomogeneous complex and functionalizes it so that it can beanchored to either an inorganic support or a polymer matrixin order to heterogenize it. However, such heterogenization iscomplicated by two factors: the immobilization process oftenappears to decrease catalytic effectiveness and the degradation ofsuch systems by the irreversible leaching of the active metal centreis almost inevitable.23 Such leaching occurs because, although thecomplex may be covalently or ionically tethered, the metal centre istypically only held within the complex by co-ordinating ligands.23

For palladium catalyzed C–C coupling reactions a number ofexamples of this approach do exist, although it is unclear to whatextent the above limitations still apply.24

The other approach is to use a more conventional supportedcatalyst typical of those used in the petrochemical and bulkchemical industries and consisting of metal nanoparticles onan oxide support. While such catalysts inherently lack the highspecifity of a homogeneous catalyst owing to the presence of avariety of active sites rather than a single active metal centre, theyoffer the considerable payback of achieving the many operationaladvantages of a truly heterogeneous catalyst as described above;the metal being relatively robustly bound to the matrix. For C–Ccoupling reactions the use of such metal nanoparticle catalysts isparticularly promising. For these reactions it has been observedthat many of the complex ligand-based monometallic§ complexes

§ It should be noted that monometallic is used throughout to refer to entitiescontaining one metal atom, which may be co-ordinated by non metallicspecies, rather than to refer to species containing only one metallic elementas is sometimes used.

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are really precursors to the actual catalyst25,26 and that in someway Pd(0) clusters are involved.27 – 30 Equally it has been claimedtheir role may still be as reservoirs for monometallic species whichform, catalyze the reaction then reabsorb into the cluster.31

Many reports of nanoparticle catalyzed C–C coupling reactionsdo already exist, however, a key mechanistic issue concerningthe identity of the active species is often overlooked and rarelydirectly addressed:32 is it the metal nanoparticles or monometallicspecies leached into solution that catalyze the reaction? Indeed,in the demonstration of polymer based monoliths containingPd nanoparticles to catalyze the Heck reaction in a flow systemunacceptably high levels of palladium could be detected in theinitial product; these were captured by a metal scavenger resin atthe reactor exit.33 For small-scale applications this is a technicallyfeasible solution but does not address whether the reactionreally occurs on the nanoparticles or that the nanoparticles servemerely as source of monometallic Pd. If the latter is in fact thecase then all the problems of separation and recovery outlinedearlier potentially remain for the heterogeneous catalysis of suchreactions.

Even when directly sought, unambiguous evidence as to thehomo- or heterogeneity of a reaction often remains elusive, withclassic tests giving a body of ‘circumstantial evidence’ which isheavily dependent on interpretation.20 It has been pointed outby Widegren and Finke34 that many of the classical tests haveshortcomings and merely observing or correlating species presentdoesn’t necessarily involve them in the cycle of the active catalyst.Where possible the most reliable results combine such data withkinetic data from a reaction.

Heck couplingIn the case of Heck reactions, evidence exists pointing to bothhetero- and homogeneity of the catalyst. Attempts to correlaterate and the presence of dissolved palladium content do indeedidentify a clear correlation.35 Leached anionic palladium speciesresulting from interactions with organic iodide have also beenisolated27 and observed to change oxidation state over thereaction; possibly indicative of their role in the catalytic cycle.36 Ifall the aryl halide is converted to PhPdI type species before theaddition of alkene the reaction also proceeds readily,37 pointingto the fact such species may well offer a pathway by whichthese reactions can proceed. Filtration38,39 and poisoning39,40

experiments also suggest the reaction proceeds via monometallicspecies in solution. A more elegant example of the probablehomogeneous nature of the reaction was provided by the use of athree phase test, originally applied to hydrogenations,41 wherebyone of the organic substrates is bound to a polymer resin sothat only a homogeneous catalyst can diffuse to the reaction site.Grafting the aryl halide to a polymer does not affect the formationof product in the reaction (for Suzuki as well as Heck couplings),42

although it has been pointed out that a potential shortcoming ofthis method is that it cannot distinguish between solution phaseclusters small enough to diffuse efficiently and truly monometallicspecies.34

In a carefully designed recent study by Rothenberg and co-workers a nanoporous alumina membrane (pore size < 11 nm)was used to demonstrate that large Pd clusters (> 11 nm) onone side of the membrane led to catalysis of the reaction onthe other.43 However, it has already been pointed out10 thatthis does not discount the transport of smaller active clustersor the re-formation of nanoparticles from monometallic specieswhich have diffused across the membrane. The formation of such

nanoparticles is particularly feasible in view of the long inductionperiod. Indeed, in a subsequent, more ambiguous study using thesame technique with a Suzuki coupling TEM analysis identifiedthe appearance of small nanoparticles in the second half of thereactor.44

Although many experiments have been described that point toHeck coupling reactions using Pd metal particles as a source of Pdmonometallic species, there is also evidence of reactions whichappear to be truly heterogeneous in nature. It was found thatthere is an excellent correlation between surface structure andactivity as particle size is varied for a range of polyvinylpyrrolidone(PVP) polymer stabilized Pd colloids (the turnover frequency beingconstant once normalized to only the edge and corner sites ofthe particles).45 In the same study it was also observed thatthe initial rate of reaction was substantially less if a Pd saltand the PVP were added separately rather than as pre-formedcolloids. This points to a role for the Pd surface sites in thereaction, although not ruling out the surface sites controllinga leaching mechanism that in turn governs a homogeneouscatalytic reaction. An interesting study has also been performedusing a Pd/PVP functionalized atomic force microscopy probe tospatially initiate a solution phase reaction of aryl halide with a self-assembled monolayer of aryl alkenes.46 Only reactants contactedwith the Pd particles on the probe react providing compellingevidence that mobile leached Pd species do not mediate thereaction in this case. However, it is difficult to ascertain if thecontact pressure of the AFM probe promotes a reaction thatwould not otherwise occur at a significant rate under theseconditions.

Suzuki couplingExperiments exploring the reaction mechanism of aryl halideswith boronic acids catalyzed by palladium nanoparticles appearon balance to point to the catalyst acting truly heterogeneously,although this may be a result of a less extensive number ofstudies and the particular reaction conditions selected. El-Sayedand co-workers identified the importance of surface sites in thereaction28 and the effect on activity of Ostwald ripening.29 Boththese factors point toward the role of the Pd surface in Suzukicoupling reactions. A study using ionic liquids showed againthat nanoparticles seemed to play a crucial role in the catalysis,with no evidence for leached Pd species (although the authorshypothesize the particles could still be acting as a reservoir of suchspecies).30

Adoption of a new approach already used to look at similarhomogeneous catalysts,47,48 in situ X-ray absorption spectroscopy(XAS), has recently allowed the nature of the active species tobe interrogated during the reaction. The reaction kinetics weremonitored by periodic sampling for offline GC analysis. In oneinstructive study of this type the authors used an unsupportedpolyvinylpyrrolidone polymer capped Pd nanoparticle catalyst.The XAS technique probes the co-ordination number of the Pdatoms and hence for the nanoparticles used in the catalyst is verysensitive to changes in particle size or dissolution of monometallicPd species. A schematic indicating the in situ technique setupis provided in Fig. 4. It was shown that Suzuki coupling can beperformed under mild conditions where Pd leaching cannot bedetected during the reaction and the nanoparticles are stablewith respect to either sintering or dissolution (corresponding toless than 1/20th of the Pd present being present as solubilizedpalladium).10,49 Furthermore, spiking of the reaction with a Pdsalt results in no sudden change in reaction rate, while a

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Figure 4. Schematic showing the coupling of a conventional glass batchreactor and a typical in situ X-ray cell with an X-ray ‘transparent’ kaptonwindow for EXAFS allowing both reaction kinetics and spectroscopy to befollowed for the same reaction (as described in Ref. 10).

mercury poisoning test stops the reaction completely.10 Thisall strongly points towards a truly heterogeneous reactionon the surface of the nanoparticles in this instance. Anotherrecent study about the effect of O2 and H2O on reduction andaggregation of a Pd(OAc)2 precursor salt under reaction conditionsindicated it was Pd(0) that was the active catalytic species, but adistinction between molecular and colloidal forms could not bedrawn.50

Sonogashira couplingThe coupling of aryl halides to an acetylene has also been foundto be catalyzed by using Pd and other metal nanoparticles9,20,51,52

similar to the reactions above. Mechanistically a PdMgLa mixedoxide has been carefully examined and appears to act as an ef-fective heterogeneous catalyst.53 The catalyst was observed to berecoverable with negligible loss of palladium and recyclable. Nev-ertheless, the possibilities of re-adsorption of the Pd after reactionor catalysis by small quantities of leached material were not ruledout. Activity was also lost after hot filtration of the reaction mixture,although without complementary testing of the recovered solidphase with fresh reactants this test has been found to be unre-liable; the filtration process can inhibit the reaction by capturingreagents, intermediates or causing a temperature drop.34

Owing to the interest in gold nanoparticle reactions,54 anda recent notable example catalyzing this reaction with a gold-ceria nanomaterial,9 the gold nanoparticle catalyzed Sonogashiracoupling reaction was investigated mechanistically with a seriesof Au/SiO2 catalysts and a number of lines of inquiry pointedto the reaction being overwhelming heterogeneous.8 As withthe Pd catalyzed Heck coupling, a significant particle size effectwas found to occur, albeit with different trends and probableorigins, pointing to the likely importance of the nanoparticlesin the catalytic process. Reaction kinetics also pointed to thegold nanoparticles being the agent responsible for catalysis withextensive deliberate leaching showing the reaction stopped whenall the gold was leached into solution. Conversely, starting witha soluble gold complex the reaction showed a long inductionperiod, as illustrated in Fig. 5, most likely due to time required forthe formation of clusters of gold atoms that were of sufficient

Figure 5. Showing the difference in kinetics (monitored as consumption ofreactant) for the reaction of iodobenzene (0.5 mmol) and phenylacetylene(0.5 mmol) [with base K2CO3 (0.3 mmol) at 145 ◦C in dimethylformamide(7.5 mL)] with a heterogeneous 20 nm particle size Au/SiO2 catalyst (�) vs.a AuCl(PPh3) salt (�), 6 mg of Au being present in each case. The latter doesnot react until after a long induction period, and then only slowly – likelydue to the formation of Au nanoparticles under the conditions of thereaction. (Data taken from Ref. 8).

size to catalyze the reaction.8 The location of the gold wasmonitored by both ICP-MS of the liquid and XPS of the solidcatalyst. The reaction was also observed to occur in vacuum ona Au(111) single crystal surface where no possibility of solutionphase chemistry exists.55 A further study of the same reaction,coupling iodobenzene to phenylacetylene, also indicated thatmetallic gold was required for the reaction and a very significantsupport effect on the selectivity occurs when the nanoparticleswere deposited on ceria rather than silica. This again points toa surface mediated catalytic process in which the solid supportinteracts with the metal nanoparticle.56

CONCLUSIONSFor both homogeneous and heterogeneous cases of reactionssuch as Heck, Suzuki and Sonogashira coupling there has beenconsiderable debate as to the nature of the actual active speciesand whether metal nanoparticles or single metal atoms in solutiondominate. However, a series of recent mechanistic studies foreach of these three reactions clearly point to the fact thatunder quite different conditions they can be made to occurtruly heterogeneously. Many operational advantages would resultfrom the heterogeneous catalysis of C–C coupling reactions,which are known to provide a convenient and strategic pathwayto join fragments within overall synthetic schemes. Furtherdevelopment and optimization of these systems is undoubtedlynecessary, however, it is clearly apparent that metal nanoparticlecatalyzed C–C coupling reactions are an attractive means for trueheterogeneous catalysis of this strategically important class ofsynthetic reactions.

ACKNOWLEDGEMENTSKB acknowledges financial support from Cambridge Universityand the SCI. Supervision by Professor R. M. Lambert during PhDwork on this topic is also acknowledged.

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REFERENCES1 Wu X-F, Anbarasan P, Neumann H and Beller M, From noble metal to

Nobel prize: palladium-catalyzed coupling reactions as key methodsin organic synthesis. Angew Chemie Int Edn 49:9047 (2010).

2 Heck RF and Nolley JP, Palladium-catalyzed vinylic hydrogensubstitution reactions with aryl, benzyl, and styryl halides. J OrgChem 37:2320 (1972).

3 Yamamoto T, Kobayashi K, Yasuda T, Zhou Z-H, Yamaguchi I,Ishikawa T, et al, Preparation of Polyacetylenes via organometallicC–C coupling reactions. Polym Bull 52:315 (2004).

4 Cusati G, Wedig A and Djakovitch L, Efficient heterogeneouslypalladium-catalyzed synthesis of Stilbenes and Bibenzyls. Lett OrgChem 6:77–81 (2009).

5 Wong K-T, Hung TS, Lin Y, Wu C-C, Lee G-H, Peng S-M, et al, Suzukicoupling approach for the synthesis of Phenylene-Pyrimidinealternating oligomers for blue light-emitting material. Org Lett4:513–516 (2002).

6 Jas G and Kirschning A, Continuous flow techniques in organicsynthesis. Chem – A Eur J 9:5708–5723 (2003).

7 Balanta A, Godard C and Claver C, Pd nanoparticles for C–C couplingreactions. Chem Soc Rev 40:4973–4985 (2011).

8 Kyriakou G, Beaumont SK, Humphrey SM, Antonetti C and Lambert RM,Sonogashira coupling catalyzed by gold nanoparticles: doeshomogeneous or heterogeneous catalysis dominate? Chem CatalChem 2:1444 (2010).

9 Gonzalez-Arellano C, Abad A, Corma A, Garcia H, Iglesias M andSanchez F, Catalysis by gold(I) and gold(III): a parallelism betweenhomo- and heterogeneous catalysts for copper-free Sonogashiracross-coupling reactions. Angew Chemie- Int Edn 46:1536–1538(2007).

10 Ellis PJ, Fairlamb IJS, Hackett SFJ, Wilson K and Lee AF, Evidence forthe surface-catalyzed Suzuki–Miyaura reaction over palladiumnanoparticles: an operando XAS study. Angew Chemie Int Edn49:1820 (2010).

11 Yamamura M, Moritani I and Murahashi S-I, The reaction ofσ -vinylpalladium complexes with alkyllithiums. Stereospecificsyntheses of olefins from vinyl halides and alkyllithiums.J Organomet Chem 91:C39–C42 (1975).

12 Tamura M and Kochi JK, Copper-catalyzed coupling of Grignardreagents and akyl halides in tetrahydrofuran solutions. J OrganometChem 42:205–228 (1972).

13 Mizoroki T, Mori K and Ozaki A, Arylation of Olefin with aryl iodidecatalyzed by palladium. Bull Chem Soc Japan 44:581 (1971).

14 Sonogashira K, Tohda Y and Hagihara N, Convenient synthesis ofacetylenes – catalytic substitutions of acetylenic hydrogen withbromoalkenes, iodoarenes, and bromopyridines. Tetrahedron Lett16:4467–4470 (1975).

15 Stille JK, The palladium-catalyzed cross-coupling reactions oforganotin reagents With organic electrophiles. Angew Chemie – IntEdn 25:508–523 (1986).

16 Miyaura N, Yanagi T and Suzuki A, The palladium-catalyzed cross-coupling reaction of phenylboronic acid with haloarenes in thepresence of bases. Synth Commun 11:513–519 (1981).

17 Yin L and Liebscher J, Carbon-carbon coupling reactions catalyzed byheterogeneous palladium catalysts. Chem Rev 107:133 (2006).

18 Diederich F and Stang PJ, Metal Catalyzed Cross-Coupling Reactions.Wiley-VCH, Weinheim (1998).

19 Barnard C, Palladium-catalyzed C–C coupling: then and now. PlatinumMet Rev 52:38–45 (2008).

20 Chinchilla R and Najera C, The Sonogashira reaction: a boomingmethodology in synthetic organic chemistry. Chem Rev 107:874(2007).

21 Corbet J-P and Mignani Gr, Selected patented cross-coupling reactiontechnologies. Chem Rev 106:2651 (2006).

22 Konigsberger K, Chen G-P, Wu RR, Girgis MJ, Prasad K, Repic O,et al, A practical synthesis of 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-ethylquinazoline and the art of removing palladium from theproducts of Pd-catalyzed reactions. Organic Process Res Dev 7:733(2003).

23 Dioos BM, Vankelecom IF and Jacobs P, Aspects of immobilisation ofcatalysts on polymeric supports. Adv Synth Catal 348:1413 (2006).

24 Corma A and Garcia H, Crossing the borders between homogeneousand heterogeneous catalysis: developing recoverable and reusablecatalytic systems. Topics Catal 48:8 (2008).

25 Phan N, Van-Der-Sluys M and Jones C, On the nature of the activespecies in palladium catalyzed Mizoroki–Heck and Suzuki–Miyaura

couplings – homogeneous or heterogeneous catalysis, a criticalreview. Adv Synth Catal 348:609 (2006).

26 Fairlamb IJS, Kapdi AR, Lee AF, Sanchez G, Lopez G, Serrano JL, et al,Mono- and binuclear cyclometallated palladium(ii) complexescontaining bridging (N,O-) and terminal (N-) imidate ligands: airstable, thermally robust and recyclable catalysts for cross-couplingprocesses. Dalton Trans pp. 3970 (2004).

27 de Vries JG, A unifying mechanism for all high-temperature Heckreactions. The role of palladium colloids and anionic species. DaltonTransactions 421–429 (2006).

28 Li Y, Hong XM, Collard DM and El-Sayed MA, Suzuki cross-couplingreactions catalyzed by palladium nanoparticles in aqueous solution.Org Lett 2:2385 (2000).

29 Narayanan R and El-Sayed MA, Effect of catalysis on the stability ofmetallic nanoparticles: Suzuki reaction catalyzed by PVP-palladiumnanoparticles. J Am Chem Soc 125:8340 (2003).

30 Fernandez F, Cordero B, Durand J, Muller G, Malbosc F, KihnY, et al, Palladium catalyzed Suzuki C–C couplings in an ionicliquid: nanoparticles responsible for the catalytic activity. DaltonTransactions 5572 (2007).

31 Zhao FY, Bhanage BM, Shirai M and Arai M, Heck reactions ofiodobenzene and methyl acrylate with conventional supportedpalladium catalysts in the presence of organic and/or inorganicbases without ligands. Chem – A Eur J 6:843–848 (2000).

32 Durand J, Teuma E and Gomez M, An overview of palladiumnanocatalysts: surface and molecular reactivity. Eur J Inorg Chem3577–3586 (2008).

33 Nikbin N, Ladlow M and Ley SV, Continuous flow ligand-free heckreactions using Monolithic Pd [0] nanoparticles. Org Process Res Dev11:458 (2007).

34 Widegren JA and Finke RG, A review of the problem of distinguishingtrue homogeneous catalysis from soluble or other metal-particleheterogeneous catalysis under reducing conditions. J Mol Catal A:Chem 198:317 (2003).

35 Kohler K, Kleist W and Prockl SS, Genesis of coordinatively unsaturatedpalladium complexes dissolved from solid precursors during Heckcoupling reactions and their role as catalytically active species. InorgChem 46:1876 (2007).

36 de Vries AHM, Parlevliet FJ, Schmieder-van de Vondervoort L,Mommers JHM, Henderickx HJW, Walet MAM, et al, A practicalrecycle of a ligand-free palladium catalyst for Heck reactions. AdvSynth Catal 344:996–1002 (2002).

37 Reetz MT and Westermann E, Phosphane-free palladium-catalyzedcoupling reactions: the decisive role of Pd nanoparticles. AngewChemie Int Edn 39:165 (2000).

38 Biffis A, Zecca M and Basato M, Metallic palladium in the Heck reaction:active catalyst or convenient precursor? Eur J Inorg Chem 1131–1133(2001).

39 Schmidt AF, Al-Halaiqa A and Smirnov VV, New approaches to heckreaction testing for homogeneity-heterogeneity. Kinetics Catal49:395–400 (2008).

40 Weck M and Jones CW, Mizorokia heck coupling using immobilizedmolecular precatalysts: leaching active species from Pd pincers,entrapped Pd salts, and Pd NHC complexes. Inorg Chem 46:1865(2007).

41 Collman JP, Kosydar KM, Bressan M, Lamanna W and Garrett T, Polymer-bound substrates: a method to distinguish between homogeneousand heterogeneous catalysis. J Am Chem Soc 106:2569 (1984).

42 Davies IW, Matty L, Hughes DL and Reider PJ, Are heterogeneouscatalysts precursors to homogeneous catalysts? J Am Chem Soc123:10139 (2001).

43 Thathagar MB, ten Elshof JE and Rothenberg G, Pd nanoclusters inC–C coupling reactions: proof of leaching. Angew Chemie – Int Edn45:2886–2890 (2006).

44 Gaikwad AV, Holuigue A, Thathagar MB, ten Elshof JE andRothenberg G, Ion- and atom-leaching mechanisms frompalladium nanoparticles in cross-coupling reactions. Chem – A Eur J13:6908–6913 (2007).

45 Le Bars Jl, Specht U, Bradley JS and Blackmond DG, A catalytic probeof the surface of colloidal palladium particles using Heck couplingreactions. Langmuir 15:7621 (1999).

46 Davis JJ, Bagshaw CB, Busuttil KL, Hanyu Y and Coleman KS, Spatiallycontrolled Suzuki and Heck catalytic molecular coupling. J Am ChemSoc 128:14135 (2006).

47 Fiddy SG, Evans J, Newton MA, Neisius T, Tooze RP and Oldman R,Extended X-ray absorption fine structure (EXAFS) characterisation

J Chem Technol Biotechnol 2012; 87: 595–600 c© 2012 Society of Chemical Industry wileyonlinelibrary.com/jctb

60

0

www.soci.org SK Beaumont

of dilute palladium homogeneous catalysts. Chem Commun2682–2683 (2003).

48 Guilera G, Newton MA, Polli C, Pascarelli S, Guino M and Hii KK, In situinvestigation of the oxidative addition in homogeneous Pdcatalysts by synchronised time resolved UVVis/XAFS. ChemCommun4306–4309 (2006).

49 Lee AF, Ellis PJ, Fairlamb IJS and Wilson K, Surface catalyzed Suzuki-Miyaura cross-coupling by Pd nanoparticles: an operando XASstudy. Dalton Trans 39:10473 (2010).

50 Adrio LA, Nguyen BN, Guilera G, Livingston AG and Hii KK, Speciationof Pd(OAc)2 in ligandless Suzuki-Miyaura reactions. Catal Sci Technol2:316–323 (2012).

51 Plenio H, Catalysts for the Sonogashira coupling – the crownless againshall be king. Angew Chemie Int Edn 47:6954 (2008).

52 Kanuru VK, Humphrey SM, Kyffin JMW, Jefferson DA, Burton JW,Armbruster M, et al, Evidence for heterogeneous Sonogashira

coupling of phenylacetylene and iodobenzene catalyzed by welldefined rhodium nanoparticles. Dalton Trans 7602–7605 (2009).

53 Cwik A, Hell Z and Figueras F, A copper-free Sonogashira reactionusing a Pd/MgLa mixed oxide. Tetrahedron Lett 47:3023 (2006).

54 Hashmi ASK and Hutchings GJ, Gold catalysis. Angew Chemie Int Edn45:7896 (2006).

55 Kanuru VK, Kyriakou G, Beaumont SK, Papageorgiou AC, Watson DJand Lambert RM, Sonogashira coupling on an extended goldsurface in Vacuo: reaction of phenylacetylene with Iodobenzene onAu(111). J Am Chem Soc 132:8081–8086 (2010).

56 Beaumont SK, Kyriakou G and Lambert RM, Identity of theactive site in gold nanoparticle-catalyzed sonogashira couplingof phenylacetylene and iodobenzene. J Am Chem Soc132:12246–12248 (2010).

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