catalysts Review ReviewSolid-Supported Palladium Catalysts in Sonogashira Solid-Supported Palladium Catalysts in Sonogashira Reactions: Recent Developments Reactions: Recent Developments Diego A. Alonso, Alejandro Baeza, Rafael Chinchilla *, Cecilia Gómez, Gabriela Guillena, IsidroDiego M. A. AlonsoPastor *ID and, Alejandro Diego J. BaezaRamónID , Rafael Chinchilla * ID , Cecilia Gómez, Gabriela Guillena, Isidro M. Pastor * ID and Diego J. Ramón ID Department of Organic Chemistry and Institute of Organic Synthesis (ISO), Faculty of Sciences, University of Alicante,Department PO ofBox Organic 99, 03080 Chemistry Alicante, and Spain Institute; [email protected] of Organic Synthesis (D.A.A.); (ISO), [email protected] Faculty of Sciences, (A.B.); University of Alicante,[email protected] PO Box (C.G.); 99, 03080 [email protected] Alicante, Spain; [email protected] (G.G.); [email protected] (D.A.A.); (D.J.R.) [email protected] (A.B.); *[email protected] Correspondence: (C.G.); [email protected] [email protected] (R.C.); [email protected] (G.G.); [email protected] (I.M.P); Tel.: (D.J.R.) +34-965-903-822 (R.C.) * Correspondence: [email protected] (R.C.); [email protected] (I.M.P); Tel.: +34-965-903-822 (R.C.) Received: 19 April 2018; Accepted: 9 May 2018; Published: 11 May 2018 Abstract:Received: 19The April Sonogashira 2018; Accepted: cross 9 May-coupling 2018; Published: reaction 11is Maythe 2018most frequently employed synthetic procedure for the preparation of arylated alkynes, which are important conjugated compounds with Abstract: The Sonogashira cross-coupling reaction is the most frequently employed synthetic multiple applications. Despite of their rather high price, this reaction is usually catalyzed by procedure for the preparation of arylated alkynes, which are important conjugated compounds palladium species, making the recovery and reuse of the catalyst an interesting topic, mainly for with multiple applications. Despite of their rather high price, this reaction is usually catalyzed by industrial purposes. Easy recycle can be achieved anchoring the palladium catalyst to a separable palladium species, making the recovery and reuse of the catalyst an interesting topic, mainly for support. This review shows recent developments in the use of palladium species anchored to industrial purposes. Easy recycle can be achieved anchoring the palladium catalyst to a separable different solid supports as recoverable catalysts for Sonogashira cross-coupling reactions. support. This review shows recent developments in the use of palladium species anchored to different solid supports as recoverable catalysts for Sonogashira cross-coupling reactions. Keywords: palladium; catalysis; Sonogashira reaction; supported reagents; cross-coupling reactions Keywords: palladium; catalysis; Sonogashira reaction; supported reagents; cross-coupling reactions 1. Introduction 1. IntroductionThe palladium-catalyzed Csp2-Csp coupling reaction between aryl or alkenyl halides or triflates and terminalThe palladium-catalyzed alkynes is the most Csp important2-Csp coupling method reaction to prepare between arylalkynes aryl or alkenyl and conjugated halides or enynes, triflates whichand terminal are precursors alkynes is for the natural most important products, method pharmaceuticals, to prepare arylalkynes and molecular and conjugatedorganic materials enynes, which(Scheme are 1) [1]. precursors The pioneering for natural works products, of Heck [2] pharmaceuticals, and Cassar [3] in and 1975, molecular using phosphine organic-palladium materials (Schemecatalysts1 at)[ temperatures1]. The pioneering up to 100 works °C, ofwere Heck improved [2] and in Cassar the same [3] in year 1975, by using Sonogashira phosphine-palladium and Hagihara, reportingcatalysts at that temperatures the addition up of to a 100 catalytic◦C, were amount improved of copper(I) in the same accelerates year by the Sonogashira reaction, thus and Hagihara,enabling toreporting achieve thatthe a thelkynylation addition ofat aroom catalytic temperature amount of[4]. copper(I) Therefore, accelerates the Sonogashira the reaction,–Hagihara thus enablingprotocol (moreto achieve often the simply alkynylation known atas room Sonogashira temperature reaction) [4]. Therefore, became the the most Sonogashira–Hagihara popular procedure protocol for the (morealkynylation often simplyof aryl knownor alkenyl as Sonogashira halides [1,5,6 reaction)]. It is interesting became the to most note popular that ma procedureny of the forrecent the developmentsalkynylation of about aryl new or alkenyl catalytic halides systems [1 able,5,6]. to Itcarry is interesting out this reaction to note are that intended many to of be the “copper recent- freedevelopments” processes, about to avoid new catalyticundesirable systems Glaser able-type to alkyne carry outhomocoupling this reaction [7] are and intended to diminish to be “copper-free”environmental processes, contamination, to avoid these undesirable processes Glaser-type however alkyne still homocouplingbeing termed [ 7]as and “Sonogashira to diminish reactionsenvironmental”. contamination, these processes however still being termed as “Sonogashira reactions”. Scheme 1. The general Sonogashira cross cross-coupling-coupling reaction reaction.. Catalysts 2018, 8, x; doi: FOR PEER REVIEW www.mdpi.com/journal/catalysts Catalysts 2018, 8, 202; doi:10.3390/catal8050202 www.mdpi.com/journal/catalysts Catalysts 2018, 8, 202 2 of 39 Catalysts 2018, 8, x FOR PEER REVIEW 2 of 38 From an economical, as well as an environmental, point of view, recovering and reusing the expensive palladium catalystcatalyst results particularlyparticularly interesting.interesting. The The obvious way of recovering the catalyst would be anchoring the catalytic species to a solid support, which would allow its easy separation afterafter the the reaction reaction completion completion just byjust simple by simple filtration, filtration, this topic this being topic considered being considered nowadays anowadays fast-moving a fast research-moving field research [8–12]. field The present[8–12]. The review present shows review recent shows developments recent developments in the Sonogashira in the reactionSonogashira carried reaction out by carried using out solid-supported by using solid palladium-supported catalysts palladium and catalysts reported and from reported 2012 till from the beginning2012 till the of beginning 2018 [13]. Theof 2018 review [13]. has The been review divided has considering been divided the considering different types the ofdifferent supports types for the of palladiumsupports for species. the palladium It is necessary species. to noteIt is that,necessary although to note in many that, cases although the real in catalystmany cases is unknown, the real palladiumcatalyst is (0)unknown, nanoparticles palladium (PdNPs) (0) nanoparticles are generally considered(PdNPs) are to generally be the active considered catalytic species,to be the most active of thecatalyt palladiumic species, complexes most of the being palladium just precursors. complexes being just precursors. 2. Organic Polymer-SupportedPolymer-Supported Palladium Catalysts Organic polymers have been the oldest recoverable supports for palladium species acting as catalyst in Sonogashira reactions, and still manymany new palladium-containingpalladium-containing organic polymers able to catalyze this cross-couplingcross-coupling reactionreaction appear.appear. ItIt isis interesting toto note that almost all these new catalysts can perform the reaction inin aa copper-freecopper-free fashionfashion (Scheme(Scheme2 2).). Scheme 2.2. A generalgeneral copper-freecopper-free Sonogashira cross-couplingcross-coupling reaction between an aryl halide and a terminal alkyne.alkyne. Polystyrene-divinylbenzene resin beads have been the most frequently employed organic Polystyrene-divinylbenzene resin beads have been the most frequently employed organic supports supports for anchoring palladium complexes. Thus, PdNPs supported on a crosslinked polystyrene for anchoring palladium complexes. Thus, PdNPs supported on a crosslinked polystyrene 1 (Figure1) 1 (Figure 1) were used as catalyst in the copper-free Sonogashira coupling of phenylacetylene with were used as catalyst in the copper-free Sonogashira coupling of phenylacetylene with aryl iodides, aryl iodides, bromides and chlorides (Scheme 2), the addition of tetra-n-butylammonium bromide bromides and chlorides (Scheme2), the addition of tetra- n-butylammonium bromide (TBAB) as (TBAB) as nanoparticle stabilizer being necessary in the case of aryl chlorides [14]. The catalyst was nanoparticle stabilizer being necessary in the case of aryl chlorides [14]. The catalyst was recovered by recovered by filtration and reused up to five times in the model reaction between iodobenzene and filtration and reused up to five times in the model reaction between iodobenzene and phenylacetylene phenylacetylene obtaining recycling yields ranging from 88% to 72%. Other case is the obtaining recycling yields ranging from 88% to 72%. Other case is the phenyldithiocarbazate Pd(II) phenyldithiocarbazate Pd(II) complex 2 (Figure 1), which catalyzes the copper-free coupling of aryl complex 2 (Figure1), which catalyzes the copper-free coupling of aryl iodides and bromides, in pyridine iodides and bromides, in pyridine as base and at room temperature under neat conditions (Scheme as base and at room temperature under neat conditions (Scheme2)[ 15]. The supported catalyst 2) [15]. The supported catalyst has been reused up to five