And Intermolecular Addition of Carboxylic Acids to Alkynes in Aqueous Media: a Review

catalysts

Review Metal-Catalyzed Intra- and Intermolecular Addition of Carboxylic Acids to Alkynes in Aqueous Media: A Review

Javier Francos and Victorio Cadierno *

Laboratorio de Compuestos Organometálicos y Catálisis (Unidad Asociada al CSIC), Centro de Innovación en Química Avanzada (ORFEO-CINQA), Departamento de Química Orgánica e Inorgánica, IUQOEM, Facultad de Química, Universidad de Oviedo, Julián Clavería 8, E-33006 Oviedo, Spain; [email protected] * Correspondence: [email protected]; Tel.: +34-985-103453

Received: 19 October 2017; Accepted: 2 November 2017; Published: 6 November 2017

Abstract: The metal-catalyzed addition of carboxylic acids to alkynes is a very effective tool for the synthesis of carboxylate-functionalized oleﬁnic compounds in an atom-economical manner. Thus, a large variety of synthetically useful lactones and enol-esters can be accessed through the intra- or intermolecular versions of this process. In order to reduce the environmental impact of these reactions, considerable efforts have been devoted in recent years to the development of catalytic systems able to operate in aqueous media, which represent a real challenge taking into account the tendency of alkynes to undergo hydration in the presence of transition metals. Despite this, different Pd, Pt, Au, Cu and Ru catalysts capable of promoting the intra- and intermolecular addition of carboxylic acids to alkynes in a selective manner in aqueous environments have appeared in the literature. In this review article, an overview of this chemistry is provided. The synthesis of β-oxo esters by catalytic addition of carboxylic acids to terminal propargylic alcohols in water is also discussed.

Keywords: aqueous catalysis; alkynes; carboxylic acids; alkynoic acids; hydrocarboxylation reactions; cycloisomerization reactions; enol esters; lactones; β-oxo esters

1. Introduction The transition metal-catalyzed heterofunctionalization of alkynes by addition of nucleophiles to the C≡C bond has emerged in recent years as a versatile synthetic tool in organic chemistry [1–3]. In particular, the addition of carboxylic acids to alkynes, reaction also referred in the literature as hydro-oxycarbonylation or hydrocarboxylation of alkynes, represents a straightforward way to obtain different types of oleﬁnic esters with atom economy [4–6]. Thus, the intramolecular version of the process, i.e., the cycloisomerization of alkynoic acids, produces unsaturated lactones (Scheme1) which are common structural motifs found in natural products and biologically active molecules, as well as valuable synthetic intermediates [7–10]. A large variety of transition metal complexes have been used to catalyze these reactions through the π-activation of the carbon-carbon triple bond of the alkynoic acid, the regioselectivity (exo or endo addition of the carboxylate to the C≡C bond leading to lactones A or B, respectively) and stereoselectivity of the process being dependent on the metal employed, the length of the hydrocarbon chain connecting the acid and alkyne units, and the terminal or internal nature of the alkyne functionality [1–6]. Among the most commonly employed metals are Pd, Ag, Au and Rh, including examples of heterogeneous systems [11], which have shown a high efﬁcacy for the selective preparation of 5-, 6-, and to a lesser extent, 7-membered ring lactones [1–6].

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Scheme 1. The catalytic cycloisomerization of alkynoic acids. Scheme 1. The catalytic cycloisomerization of alkynoic acids. The intermolecular addition of carboxylic acids to alkynes also presents enormous interest sinceThe the intermolecularintermolecularreaction products, additionaddition i.e., enol of of carboxylic carboxylicesters (C acids oracids D to in alkynesto Scheme alkynes also 2), also presentsare presentsversatile enormous enormousbuilding interest blocks interest since in sincetheorganic reaction the synthesis reaction products, andproducts, material i.e., enol i.e., science. esters enol (esters CForor example,D (Cin or Scheme D toin name Scheme2), are just versatile 2), a few are ofversatile building their myriad building blocks applications, in blocks organic in organicsynthesisthey are synthesis andwidely material and employed material science. science.as For mild example, For acylating example, to name toreagents justname a fewjust [12,13], a of few their ofas myriadtheir monomers myriad applications, applications,in diverse they theyarepolymerization widely are widely employed reactions employed as mild[14–16], acylatingas asmild substrates reagentsacylating in [asymmetric 12reagents,13], as monomers hydrogenation[12,13], as in diversemonomers for the polymerization generation in diverse of polymerizationreactionsenantioenriched [14–16 reactions], alcohols as substrates [14–16],[17–19], in asymmetricas or substrates as starting hydrogenation in materialsasymmetric for for hydrogenation different the generation cross-coupling for of the enantioenriched generation processes of enantioenrichedalcohols[20–22]. As [17 –for19], thealcohols or ascycloisomerization starting [17–19], materials or as ofstarting for alkynoic different materials acids, cross-coupling fora hugedifferent number processes cross-coupling of [ 20catalytic–22]. Asprocesses systems for the [20–22].cycloisomerizationinvolving As late for transition the of cycloisomerization alkynoic metals acids, have abeen hugeof alkynoicdescribed, number acids, of with catalytic athose huge systems based number on involving rutheniumof catalytic late transitionplaying systems a involvingmetalsprominent have late role been transition[1–5]. described, However, metals with for thosehave a long basedbeen time, described, on rutheniumthis reaction with playing thosewas limited abased prominent toon terminal ruthenium role [1 alkynes,–5]. playing However, since a prominentformost a longcatalysts time,role failed [1–5]. this reactionto However, enable was the for limitedhydrocarboxylati a long totime, terminal thison reaction alkynes, of internal was since alkyneslimited most toas catalysts terminala consequence failed alkynes, to of enable sincetheir mostthegreater hydrocarboxylation catalysts steric hindrance, failed to enable of which internal the disf hydrocarboxylati alkynesavours astheir a consequence coordinationon of internal of to their the alkynes greatermetal as catalyst. sterica consequence hindrance, At this point,of which their it greaterdisfavoursshould stericbe noted their hindrance,coordination that a reducedwhich to disf thereacavours metaltivity catalyst.their of internal coordination At thisvs. point,terminal to the itshould metalC≡C bondscatalyst. be noted is Atalso that this commonly a reducedpoint, it shouldreactivityobserved be ofin noted internalthe cyclization that vs. a terminalreduced reactions Creac≡C oftivity bonds alkynoic of is internal also acids, commonly vs.although terminal observed in thisC≡C case in bonds the the cyclization isproblem also commonly reactionsis not so observedofmarked alkynoic as in the acids, the intramolecular cyclization although inreactions thisprocess case ofis the muchalkynoic problem mo acre is ids,favoured not although so marked from in a asthisthermodynamic the case intramolecular the problem pointprocess is of not view. so is markedmuchFortunately, more as the favoured recent intramolecular works from focused a thermodynamic process in theis much design point mo ofre ofincreasingly favoured view. Fortunately, from active a thermodynamic catalysts recent works have made focusedpoint possibleof inview. the Fortunately,designto overcome of increasingly recentthis limitation works active focused catalystsand some in the have Ru-, design made Pd-, of possibleAg- increasingly and to Au-based overcome active systemscatalysts this limitation activehave made andwith some possibleinternal Ru-, toPd-,alkynes overcome Ag- are and now Au-basedthis available limitation systems [23]. and active some with Ru-, internal Pd-, Ag- alkynes and Au-based are now available systems [ 23active]. with internal alkynes are now available [23].

Scheme 2. The intermolecular addition of carboxylic acids to alkynes. Scheme 2. The intermolecular addition of carboxylic acids to alkynes. On the other hand, the increasing awareness of environmental concerns has stimulated the On the other hand, the increasing awareness of environmental concerns has stimulated the developmentOn the other of metal-catalyzed hand, the increasing reactions awareness in aque ousof environmental media, since concernswater is cheaper,has stimulated safer andthe development of metal-catalyzed reactions in aqueous media, since water is cheaper, safer and benigner developmentbenigner compared of metal-catalyzed to the traditional reactions petroleum-de in aquerivedous media, organic since solvents water [24–26]. is cheaper, In addition, safer andthe compared to the traditional petroleum-derived organic solvents [24–26]. In addition, the use of benigneruse of water compared (or aqueous to the traditional biphasic petroleum-demixtures) allowsrived inorganic many solventscases an [24–26]. easy catalyst/productIn addition, the water (or aqueous biphasic mixtures) allows in many cases an easy catalyst/product separation, thus useseparation, of water thus (or allowing aqueous the biphasic effective mixtures)recycling ofallows the catalytically in many casesactive anspecies, easy whichcatalyst/product is another allowing the effective recycling of the catalytically active species, which is another key aspect in the separation,key aspect inthus the allowing Green Chemistry the effective context recycling [27]. ofHo thewever, catalytically despite theactive growing species, interest which in is aqueousanother Green Chemistry context [27]. However, despite the growing interest in aqueous catalysis, the use of keycatalysis, aspect the in usethe ofGreen this environmentallyChemistry context benign [27]. Hosolventwever, in despitethe hydrocarboxylation the growing interest of alkynes in aqueous been this environmentally benign solvent in the hydrocarboxylation of alkynes been for long time neglected, catalysis,for long timethe use neglected, of this environmentally probably due to benign the co solventncerns inof the a competinghydrocarboxylation hydration of of alkynes the alkyne been probably due to the concerns of a competing hydration of the alkyne substrates to form carbonyl forsubstrates long time to form neglected, carbonyl probably compounds, due ato process the co thatncerns is also of acatalyzed competing by transitionhydration metals of the [1–6,28]. alkyne compounds, a process that is also catalyzed by transition metals [1–6,28]. In fact, in a general review substratesIn fact, in a to general form carbonyl review on compounds, the “catalytic a process reactions that of is alkynes also catalyzed in water”, by publishedtransition metalsby Chen [1–6,28]. and Li on the “catalytic reactions of alkynes in water”, published by Chen and Li in 2006, no examples of Inin fact,2006, in no a generalexamples review of hydrocarboxylation on the “catalytic reactions reactions of were alkynes collected in water”, [28]. published Catalytic systemsby Chen ableand Lito hydrocarboxylation reactions were collected [28]. Catalytic systems able to operate selectively in inoperate 2006, selectivelyno examples in ofaqueous hydrocarboxylation environments reactions have on lywere appeared collected in [28].the literatureCatalytic insystems recent able years, to aqueous environments have only appeared in the literature in recent years, and are the subject of operateand are selectivelythe subject inof aqueousthe present environments review article. have Intra- only andappeared intermolecular in the literature processes in recentare covered, years, the present review article. Intra- and intermolecular processes are covered, including examples of and are the subject of the present review article. Intra- and intermolecular processes are covered,

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including examples of sequential transformations of synthetic interest. The access to β-oxo esters by sequential transformations of synthetic interest. The access to β-oxo esters by the catalytic addition of the catalytic addition of carboxylic acids to terminal propargylic alcohols in water is also discussed. carboxylic acids to terminal propargylic alcohols in water is also discussed. Catalysts 2017, 7, 328 3 of 23 2. Intramolecular Processes 2. Intramolecularincluding examples Processes of sequential transformations of synthetic interest. The access to β-oxo esters by the catalytic addition of carboxylic acids to terminal propargylic alcohols in water is also discussed. 2.1. Cycloisomerization of Preformed or In Situ Generated Alkynoic Acids The2. Intramolecular ﬁrstfirst exampleexample Processes of suchsuch reactionsreactions in anan aqueousaqueous environmentenvironment was describeddescribed by Hidai and co-workers inin 19961996 employingemploying thethe mixed-metal mixed-metal cubane-type cubane-type cluster cluster complex complex [PdMo [PdMoS3S(tacn)4(tacn)Cl][PF3Cl][PF6]]3 2.1. Cycloisomerization of Preformed or In Situ Generated Alkynoic Acids 3 4 3 6 3 ((1;; tacntacn = 1,4,7-triazacyclononane) 1,4,7-triazacyclononane) as as catalyst catalyst [29]. [29]. Thus, Thus, they they found found that, that, in in combination combination with with NEt NEt3, 31, 1waswas able ableThe toto transformfirsttransform example dipropargylmalonic dipropargylmalonic of such reactions in acid an acid 2aqintoueous 2 theinto environment enol the lactone enol was3lactonein described water 3 atin roomby water Hidai temperature atand room (Schemetemperatureco-workers3). Unfortunately, (Scheme in 1996 3).employing Unfortunatel although the mixed-me they, although ratetal and cubane-type the yield rate of and cluster the yield reaction complex of the were [PdMoreaction very3S4(tacn) were similar3 Cl][PFvery to similar6] those3 (1; tacn = 1,4,7-triazacyclononane) as catalyst [29]. Thus, they found that, in combination with NEt3, 1 observedto those observed in acetonitrile, in acetonitrile, this latter this solvent latter was solven selectedt was by selected the authors by the to studyauthors the to scope study of the the scope process. of was able to transform dipropargylmalonic acid 2 into the enol lactone 3 in water at room Inthe this process. regard, In different this regard, 5-, 6- different and 7-membered 5-, 6- and ring7-membered lactones couldring lactones be obtained could from be obtained the corresponding from the temperature (Scheme 3). Unfortunately, although the rate and yield of the reaction were very similar corresponding alkynoic acids with complex 1, which showed an enhanced reactivity in comparison alkynoicto those acids observed with complex in acetonitrile,1, which this latter showed solven ant enhancedwas selected reactivity by the auth inors comparison to study the with scope classical of mononuclearwith theclassical process. Pd(II)mononuclear In this sources, regard, Pd( different suchII) sources, as 5-, [PdCl 6- and such2(PhCN) 7- memberedas [PdCl2] or2 Na (PhCN)ring2[PdCl lactones2] 4or]. couldNa In line2[PdCl be withobtained4]. In this, line from despite with the this, the presencedespitecorresponding the of presence three molybdenum alkynoic of three acids moly with atomsbdenum complex in the atoms 1 structure, which in showedthe of structure1, the an enhanced catalytic of 1, the reactionsreactivity catalytic in were comparison reactions assumed were to proceedassumedwith only toclassical proceed at the mononuclear palladium only at the center.Pd( palladiumII) sources, center. such as [PdCl2(PhCN)2] or Na2[PdCl4]. In line with this, despite the presence of three molybdenum atoms in the structure of 1, the catalytic reactions were assumed to proceed only at the palladium center.

Scheme 3. Cyclosiomerization of dipropargylmalonic acid 2 in water usingusing aa clustercluster catalyst.catalyst. Scheme 3. Cyclosiomerization of dipropargylmalonic acid 2 in water using a cluster catalyst. More recently, otherother palladium-basedpalladium-based catalysts for the cyclizationcyclization of alkynoic acids in aqueous More recently, other palladium-based catalysts for the cyclization of alkynoic acids in aqueous media havehave been been described. described. In particular, In particular, García- ÁlvarezGarcía-Álvarez and co-workers and disclosedco-workers that disclosed transformation that media have been described. In particular, García-Álvarez and co-workers disclosed that oftransformationγ-alkynoic acids of γ into-alkynoic ﬁve-membered acids into ringfive-membered enol-lactones ring (5- enol-lactonesexo-dig cyclization) (5-exo- candig becyclization) conveniently can be convenientlytransformation and of γselectively-alkynoic acids achieved into five-membered in pure water, ring andenol-lactones under aerobic (5-exo-dig conditions, cyclization) by can using and selectivelybe conveniently achieved and selectively in pure water, achieved and in under pure water, aerobic and conditions, under aerobic by usingconditions, catalytic by using amounts catalytic amounts of the dinuclear Pd(II) derivative2 trans-[PdCl2{µ2-N,S-(PTA)=NP(=S)(OEt)2}]2 (4) of thecatalytic dinuclear amounts Pd(II) of derivativethe dinucleartrans Pd(II)-[PdCl derivative2{µ -N,S trans-(PTA)=NP(=S)(OEt)-[PdCl2{µ2-N,S-(PTA)=NP(=S)(OEt)2}]2 (4) (Scheme2}]2 4(4)) [ 30]. This(Scheme(Scheme catalyst 4) [30]. 4) features [30]. This This catalyst a catalyst bridging features features iminophosphorane-type a a bridgi bridgingng iminophosphorane-type ligand derived ligand ligand from derived derived the from well-known from the the hydrophilicwell-knownwell-known phosphinehydrophilic hydrophilic PTA phosphine (1,3,5-triaza-7-phosphaadamantane) phosphine PTAPTA (1,3,5(1,3,5-triaza-7-phosphaadamantane)-triaza-7-phosphaadamantane) [31,32], which facilitates [31,32], [31,32], itswhich solubility which infacilitates water.facilitates its solubility its solubility in water.in water.

SchemeScheme 4. Cycloisomerization4. Cycloisomerization of differentof differentγ-alkynoic γ-alkynoic acids acids in waterin water catalyzed catalyzed by aby dinuclear a Pd(II)dinuclear complex. Pd(II) complex. Scheme 4. Cycloisomerization of different γ-alkynoic acids in water catalyzed by a dinuclear Pd(II) complex.

Catalysts 2017, 7, 328 4 of 23

Catalysts 2017, 7, 328 4 of 23 As shown in Scheme4, the reactions proceeded cleanly at r.t. (room temperature) without As shown in Scheme 4, the reactions proceeded cleanly at r.t. (room temperature) without formation of any by-product derived from the hydration of the C≡C bond of the substrates or formation of any by-product derived from the hydration of the C≡C bond of the substrates or from from the hydrolysis of the (Z)-γ-alkylidene butyrolactone products. The process was operative with the hydrolysis of the (Z)-γ-alkylidene butyrolactone products. The process was operative with γ-alkynoic acids containing both terminal and internal C≡C bonds, although for the latter a much γ-alkynoic acids containing both terminal and internal C≡C bonds, although for the latter a much longer reaction time was needed (24 instead of 0.5–2 h). It is also worth noting that (i) this catalytic longer reaction time was needed (24 instead of 0.5–2 h). It is also worth noting that (i) this catalytic systemsystem could could be be recycled recycled up up to to 10 10 consecutive consecutive runsruns for the the cyclization cyclization of of the the model model 4-pentynoic 4-pentynoic acid acid (cumulative(cumulative TON TON (turnover (turnover number) number) ofof 982),982), andand (ii) it could could be be applied applied in in the the desymmetrization desymmetrization of of bispropargylicbispropargylic carboxylic carboxylic acids acids5 5,, affording affording enol-lactonesenol-lactones 66 containingcontaining an an intact intact propargylic propargylic side side arm arm inin excellent excellent yields. yields. AlthoughAlthough in in a a limitedlimited numbernumber of of examples examples (onl (onlyy six six substrates substrates were were explored), explored), the group the group of ofNakamura Nakamura also also demonstrated demonstrated the the capacity capacity of of the the NCN-pincer NCN-pincer Pd(II) Pd(II) derivative derivative 7 (Figure7 (Figure 1)1 to) to promotepromote the the high-yield high-yield formation formation of of ﬁve-membered five-membered ring lactones from from both both γγ- -and and β-alkynoicβ-alkynoic acids acids (5-(5-exoexo-dig-digand and 5- endo5-endo-di-digg cyclization, cyclization, respetively)respetively) in pure water [33]. [33]. Complex Complex 7 7easilyeasily generates generates hydrogen-bonding-basedhydrogen-bonding-based supramolecular supramolecular gels, with well-organized well-organized Pd-arrays, Pd-arrays, in inorganic organic solvents. solvents. ◦ ForFor the the catalytic catalytic reactions, reactions, whichwhich werewere performed at at 70 70 °CC and and in inthe the presence presence of Et of3N Et (33N mol (3 mol%), a %), a water-insolublewater-insoluble xerogel xerogel prepared prepared from from 7 7inin toluene toluene was was employed employed (0.5 (0.5 mol mol % %Pd Pd content). content). Interestingly,Interestingly, the the Pd-gel Pd-gel catalyst catalyst couldcould bebe recoveredrecovered by by filtration ﬁltration and and reused reused three three times times in inthe the cyclizationcyclization of 4-pentynoicof 4-pentynoic acid acid without without loss ofloss catalytic of catalytic activity. activity. However, However, it should it alsoshould be mentionedalso be that,mentioned contrary that, to the contrary case of to the the dinuclear case of Pd(II)the dinuclear complex Pd(II)4, when complex a bispropargylic 4, when a bispropargylic carboxylic acid carboxylic acid was employed as substrate, partial hydration of propargylic side arm of the was employed as substrate, partial hydration of propargylic side arm of the enol-lactone product enol-lactone product was observed. was observed.

Figure 1. Structure of the pincer palladium(II) complexes 7 and 8. Figure 1. Structure of the pincer palladium(II) complexes 7 and 8.

SelectiveSelective 5- exo5-exo-dig-digcyclization cyclization of of pentynoic pentynoic acidsacids RCRC≡≡CCHCCH22CHCH2CO2CO2H2 H(R (R= =aryl aryl or orheteroaryl heteroaryl group)group) to to afford afford the the corresponding corresponding (Z ()-Zγ)--alkylideneγ-alkylidene butyrolactones butyrolactones could could alsoalso bebe achieved,achieved, in water at 50 at◦C, 50 using °C, theusing related the related amphiphilic amphiphilic NCN-pincer NCN-pincer Pd(II) complexPd(II) complex8 (2 mol 8 %) (2 (Figure mol %)1) in(Figure combination 1) in combination with Et3N (6 mol %) (yields in the range 38–94% after 1–6 h) [34]. Complex 8 with Et3N (6 mol %) (yields in the range 38–94% after 1–6 h) [34]. Complex 8 self-assembles in aqueous solutionself-assembles forming in bilayered aqueous vesicles solution which forming were bilayere foundd to vesicles be essential which for were the found promotion to be ofessential the catalytic for processthe promotion (markedly of lower the catalytic yields were process obtained (markedl wheny lower the same yields reactions were obtained were performed when the in organicsame solventsreactions or employingwere performed the amorphous in organic solv complexents or8 employingin water). the amorphous complex 8 in water). On the other hand, despite the well-known ability of platinum compounds to promote the On the other hand, despite the well-known ability of platinum compounds to promote the cycloisomerization of polyunsaturated organic molecules [35,36], this metal has been much less used cycloisomerization of polyunsaturated organic molecules [35,36], this metal has been much less than palladium to catalyze the cyclization of alkynoic acids [37]. In this regard, the work published used than palladium to catalyze the cyclization of alkynoic acids [37]. In this regard, the work by Alemán, Navarro-Ranninger and co-workers merits highlighting [38]. These authors evaluated published by Alemán, Navarro-Ranninger and co-workers merits highlighting [38]. These authors the catalytic behaviour of a broad family of anticancer platinum(II) and platinum(IV) evaluatedamino-complexes the catalytic (9a–jbehaviour and 9k–o, respectively; of a broad familysee Figure of 2) anticancer in the cycloisomerization platinum(II) and of 4-pentynoic platinum(IV) amino-complexesacid into 5-methylene-dihydrofuran-2-one (9a–j and 9k–o, respectively; (5-exo see-dig Figure cyclization),2) in the cycloisomerizationfinding that both the of 4-pentynoicoxidation

Catalysts 2017, 7, 328 5 of 23

Catalysts 2017, 7, 328 5 of 23 Catalysts 2017, 7, 328 5 of 23 acid into 5-methylene-dihydrofuran-2-one (5-exo-dig cyclization), finding that both the oxidation statestatestate of ofof the thethe metal metalmetal and andand the thethe stereochemistry stereochemistrystereochemistry ofofof thethethe complexcocomplexmplex areare keykey key factorsfactors factors forfor for thethe the reactionreaction reaction toto to proceedproceed proceed efficiently.efficiently.efficiently. Thus, Thus,Thus, while whilewhile the thethecis ciscis-platinum(II)-platinum(II)-platinum(II) derivativesderivativesderivatives 9a9a–––eee showedshowedshowed aa a highhigh high reactivityreactivity reactivity inin in acetoneacetone acetone atat at r.t.,r.t.,r.t., their theirtheirtrans transtrans-platinum(II)-platinum(II)-platinum(II) counterparts counterpartscounterparts 9f9f9f––jj andand the the Pt(IV)Pt(IV) speciesspecies species 9k9k9k––o–o o (regardless(regardless(regardless ofof of theirtheir their cisciscis oror or transtranstransconfiguration) configuration)configuration) turned turnedturned out outout to toto be bebe practically practicallypractically inactive. inactive.inactive.

Figure 2. Structure of the platinum complexes 9a–o. FigureFigure 2.2. StructureStructure ofof thethe platinumplatinum complexescomplexes 9a9a––oo..

InInIn addition, addition,addition, they theythey also alsoalso demonstrated demonstrateddemonstrated thethethe possibilitypossibpossibilityility ofof of usingusing using waterwater water (or(or (or eveneven even bloodblood blood plasma)plasma) plasma) asas as solvent.solvent.solvent. In In fact,In fact,fact, the thethe scope scopescope of the ofof catalyticthethe catalyticcatalytic reaction rereactionaction was waswas explored exploredexplored in water inin waterwater using usingusing complexes complexescomplexes9a,b [9a9a38,,b,b39 ]. Thus,[38,39].[38,39]. as shown Thus,Thus, asas in shownshown Scheme inin5 SchemeScheme, different 5,5, differentdifferent 5- and 6-membered 5-5- andand 6-membered6-membered ring lactones ringring lactoneslactones could couldcould be synthesized bebe synthesizedsynthesized with thesewithwith complexes, thesethese complexes,complexes, although althoughalthough mixtures mixturesmixtures of regioisomers ofof regioiregioisomerssomers were systematically werewere systematicallysystematically formed formedformed starting startingstarting from internal fromfrom alkynes.internalinternal On alkynes.alkynes. the other OnOn hand, thethe otherother it is also hand,hand, worth itit isis noting alsoalso worthworth that the notingnoting attempt thatthat made thethe attempt toattempt generate mademade a seven-membered toto generategenerate aa seven-membered ring lactone with this type of catalysts failed. ringseven-membered lactone with this ring type lactone of catalysts with this failed. type of catalysts failed.

SchemeSchemeScheme 5. 5.5.Cyclization CyclizationCyclization of ofofdifferent differentdifferent alkynoic alkynoicalkynoic acids acids inin waterwater usingusing using Pt(II)Pt(II) Pt(II) complexes.complexes. complexes.

Catalysts 2017, 7, 328 6 of 23 Catalysts 2017, 7, 328 6 of 23 Gold compounds are currently recognized as the most effective systems for the electrophilic π-activation of unsaturated carbon–carbon bonds [40,41], and, in 2006, Michelet and co-workers Gold compounds are currently recognized as the most effective systems for the electrophilic demonstrated for the first time their usefulness in the cycloisomerization of acetylenic acids [42]. The π-activation of unsaturated carbon–carbon bonds [40,41], and, in 2006, Michelet and co-workers same group was also a pioneer in the use of gold catalysts in aqueous environments. In particular, in demonstrated for the ﬁrst time their usefulness in the cycloisomerization of acetylenic acids [42]. 2008, they reported on the tolerance of the heterogeneous system Au2O3 towards the presence of The same group was also a pioneer in the use of gold catalysts in aqueous environments. water during the cycloisomerization of 2-phenyl-4-pentynoic acid into In particular, in 2008, they reported on the tolerance of the heterogeneous system Au2O3 5-methylene-3-phenyl-dihydrofuran-2-one (92% yield performing the reaction in MeCN-H2O (6:1) at towards the presence of water during the cycloisomerization of 2-phenyl-4-pentynoic acid into r.t. with 2.5 mol % of Au2O3 for 3 h; 95% yield when acetonitrile was employed alone under identical 5-methylene-3-phenyl-dihydrofuran-2-one (92% yield performing the reaction in MeCN-H2O (6:1) reaction conditions) [43]. Since then, a number of gold-based catalysts capable of operating in pure at r.t. with 2.5 mol % of Au2O3 for 3 h; 95% yield when acetonitrile was employed alone under water or in aqueous biphasic mixtures have been described, most involving functionalized identical reaction conditions) [43]. Since then, a number of gold-based catalysts capable of operating N-heterocyclic carbenes (NHC) as auxiliary ligands. In this regard, the groups of Michelet, Cadierno in pure water or in aqueous biphasic mixtures have been described, most involving functionalized and Conejero developed the zwitterionic Au(III)-NHC complex 10b which proved to be active in the N-heterocyclic carbenes (NHC) as auxiliary ligands. In this regard, the groups of Michelet, Cadierno cycloisomerization of a broad range of γ-alkynoic acids under biphasic toluene/water conditions and Conejero developed the zwitterionic Au(III)-NHC complex 10b which proved to be active in the (Scheme 6) [44]. Remarkably, the participation of a silver(I) co-catalyst, usually employed in catalytic cycloisomerization of a broad range of γ-alkynoic acids under biphasic toluene/water conditions gold chemistry to generate vacant coordination sites on the metal through chloride ligands (Scheme6)[44]. Remarkably, the participation of a silver(I) co-catalyst, usually employed in catalytic abstraction, was not required. Also of note is the fact that, despite the well-known ability of gold gold chemistry to generate vacant coordination sites on the metal through chloride ligands abstraction, complexes to promote the hydration of alkynes, competitive hydration processes were not observed was not required. Also of note is the fact that, despite the well-known ability of gold complexes under the biphasic conditions employed, even during the cycloisomerization of bispropargylic to promote the hydration of alkynes, competitive hydration processes were not observed under substrates. However, it should be noted that, if pure water is used as solvent, partial hydrolysis of the biphasic conditions employed, even during the cycloisomerization of bispropargylic substrates. the lactone products takes place, making the use of biphasic conditions more advantageous. In However, it should be noted that, if pure water is used as solvent, partial hydrolysis of the lactone general, the reactions proceeded in air under very mild temperature conditions (r.t.), except with products takes place, making the use of biphasic conditions more advantageous. In general, the those substrates containing internal C≡C bonds which showed a markedly lower reactivity and reactions proceeded in air under very mild temperature conditions (r.t.), except with those substrates required of heating at 80 °C. Concerning the regioselectivity of the process, 5-membered ring containing internal C≡C bonds which showed a markedly lower reactivity and required of heating at enol-lactones were selectively formed when terminal C≡C bonds were involved in the cyclization 80 ◦C. Concerning the regioselectivity of the process, 5-membered ring enol-lactones were selectively process. On the other hand, although the 5-exo-dig cyclization was also the preferred reaction formed when terminal C≡C bonds were involved in the cyclization process. On the other hand, pathway with internal alkynes, mixtures containing the corresponding 5- and 6-membered ring although the 5-exo-dig cyclization was also the preferred reaction pathway with internal alkynes, lactones were in some cases obtained. mixtures containing the corresponding 5- and 6-membered ring lactones were in some cases obtained.

Scheme 6.6. CyclosiomerizationCyclosiomerization of different γ-alkynoic acids catalyzedcatalyzed byby thethe Au(III)-Au(III)-NN-heterocyclic-heterocyclic 10b carbenes (NHC) complex 10b..

Catalysts 2017, 7, 328 7 of 23 Catalysts 2017, 7, 328 7 of 23

This initialinitial workwork withwith 10b10b waswas subsequentlysubsequently extendedextended toto otherother Au(III)Au(III) andand Au(I)Au(I) complexescomplexes containingcontaining relatedrelated zwitterioniczwitterionic NHCNHC ligandsligands bearingbearing 3-sulfonatopropyl,3-sulfonatopropyl, and 2-pyridyl,2-pyridyl, 2-pycolyl2-pycolyl or pyridylethylpyridylethyl substituents (10a,c and 11a–c inin FigureFigure3 3))[ [45].45]. All of themthem provedproved toto bebe catalyticallycatalytically active,active, even with Au Au loadings loadings of of only only 0.1 0.1 mol mol %, %, showing showing in in general general performances performances similar similar to tothat that of of10b10b. Interestingly,. Interestingly, all all these these gold-carbenes gold-carbenes showed showed a avery very high high recyclability recyclability (up (up to 10 consecutiveconsecutive runs)runs) byby simplesimple phasephase separationseparation (the(the goldgold catalystcatalyst remainedremained inin thethe aqueousaqueous phasephase whilewhile thethe lactonelactone productproduct waswas completely completely dissolved dissolved in thein toluenethe toluene one). one). In this In regard, this regard, some differences some differences were observed were betweenobserved the between Au(I) and the Au(III)Au(I) and species, Au(III) the recyclabilityspecies, the ofrecyclability the latter being of the much latter more being effective much due more to theireffective higher due stability to their inhigher the aqueous stability medium in the aqueous (the Au(I) medium derivatives (the Au(I)11a–c derivativesundergo with 11a–c time undergo partial decompositionwith time partial into decomposition catalytically inactive into catalytically Au(0) nanoparticles; inactive a Au(0) process nanoparticles; also observed a with process10a– calsobut whichobserved takes with place 10a much–c but more which slowly). takes place much more slowly).

Figure 3. Structure of the zwitterionic Au(III)- and Au(I)-NHCAu(I)-NHC complexescomplexes 10,11a10,11a––cc..

A goodgood recyclabilityrecyclability waswas alsoalso reportedreported byby PleixatsPleixats andand co-workersco-workers forfor thethe sol-gelsol-gel immobilizedimmobilized Au(I)-NHCAu(I)-NHC complexcomplex12 12(Scheme (Scheme7)[ 7)46 [46].]. This This organometallic organometallic hybrid hybrid silica silica material material proved proved to be activeto be inactive the cycloisomerizationin the cycloisomerization of different of differentγ-alkynoic γ-alkynoic acids at acids room at temperature room temperature using, as using, in the previousas in the example,previous example, a toluene/water a toluene/water biphasic biphasic system andsystem in the and absence in the absenc of silvere of salts. silver However, salts. However, due to due the heterogeneousto the heterogeneous nature ofnature12, longer of 12, reactionlonger reaction times and times a wrist-type and a wrist-type shaker stirring shaker (which stirring allows (which a goodallows mixing a good of mixing the immiscible of the immiscible layers and layers the insoluble and the catalyst) insoluble were catalyst) in this were case required in this case to obtain required the enol-lactoneto obtain the products enol-lactone in high products yields (no in reactionhigh yields was (no observed reaction using was conventional observed using magnetic conventional stirring). Concerningmagnetic stirring). the regioselectivity Concerning the of the regioselectivity process, ﬁve-membered of the process, enol-lactones five-membered were enol-lactones selectively formed were startingselectively from formed substrates starting with from terminal substrates alkyne with units, terminal while alkyne a mixture units, of while the 5- a and mixture 6-membered of the 5- ringand lactone6-membered products ring was lactone obtained products from was an internalobtained diyne from (Scheme an internal7). diyne (Scheme 7). For itsits part,part, thethe groupgroup ofof KrauseKrause describeddescribed thethe preparationpreparation ofof thethe ammoniumammonium salt-taggedsalt-tagged Au(I)-NHCAu(I)-NHC complexes 13a13a––ff (Figure(Figure 44)) and their application application in in the the selective selective 5- 5-exoexo-dig-dig cyclizationcyclization of ofγ-alkynoicγ-alkynoic acids acids bearing bearing a aterminal terminal alkyne alkyne unit unit in in pure pure water, water, or or in aqueousaqueous triethylammoniumtriethylammonium bufferbuffer solutionsolution [[47].47]. The catalytic reactions proceede proceededd cleanly cleanly at at r.t., in short time spans (0.5–6 h), employingemploying 2.52.5 molmol % of these complexes, with yields higher in general when the buffer solution was employedemployed as thethe reactionreaction mediummedium (partial(partial decompositiondecomposition of thethe goldgold complexescomplexes waswas observedobserved inin purepure water).water). Once again, no Ag(I) co-catalysts werewere needed and the catalysts could be reusedreused afterafter extractionextraction ofof thethe lactonelactone productproduct fromfrom thethe aqueousaqueous solutionsolution withwith diethyldiethyl etherether (up(up toto 55 times).times).

Catalysts 2017, 7, 328 8 of 23 CatalystsCatalysts 20172017,, 77,, 328328 88 ofof 2323

Scheme 7. Cyclosiomerization of γ-alkynoic-alkynoic acids using a sol-gel immobilized Au(I)-NHC complex. Scheme 7. Cyclosiomerization of γ-alkynoic acids using a sol-gel immobilized Au(I)-NHC complex.

Figure 4. Structure of the water-soluble gold(I)-NHC complexes 13a–f. Figure 4. Structure of the water-soluble gold(I)-NHCgold(I)-NHC complexescomplexes 13a13a––ff..

Interestingly, starting from the internal alkynoic acid 14, a synthetic route to obtain the Interestingly,Interestingly, startingstarting fromfrom thethe internalinternal alkynoicalkynoic acidacid 1414,, aa syntheticsynthetic routeroute toto obtainobtain thethe furanocoumarin-functionalized lactone 15, an epimer of the natural product clausemarine A, could furanocoumarin-functionalizedfuranocoumarin-functionalized lactone lactone15 15, an, an epimer epimer of of the the natural natural product product clausemarine clausemarine A, couldA, could be be developed by Krause and co-workers [47]. As shown in Scheme 8, formation of the lactone ring developedbe developed by Krauseby Krause and and co-workers co-workers [47]. [47]. As shownAs shown in Scheme in Scheme8, formation 8, formation of the of lactone the lactone ring wasring was successfully achieved by cycloisomerization of 14 with 1 mol % of 13b in an aqueous successfullywas successfully achieved achieved by cycloisomerization by cycloisomerization of 14 with of 1 mol 14 %with of 13b 1 inmol an aqueous% of 13b triethylammonium in an aqueous triethylammonium buffer solution containing THF (tetrahydrofuran) as co-solvent. buffertriethylammonium solution containing buffer THFsolution (tetrahydrofuran) containing THF as (tetrahydrofuran) co-solvent. as co-solvent.

Catalysts 2017, 7, 328 9 of 23 Catalysts 2017, 7, 328 9 of 23 Catalysts 2017, 7, 328 9 of 23

SchemeScheme 8.8. Synthesis of 2-epiepi-clausemarine-clausemarine A.A.

Besides the Au-NHC complexes commented above, the PTA-derived iminophosphorane-Au(I) Besides the Au-NHC complexes commented above,above, the PTA-derived iminophosphorane-Au(I) derivative 16 (Figure 5) proved to be also an active and selective catalyst for the 5-exo-dig cyclization derivative 16 (Figure(Figure5 5)) proved proved to to be be also also an an active active and and selective selective catalyst catalyst for for the the 5- 5-exoexo--digdig cyclizationcyclization of 4-pentynoic acid in water (89% yield after 30 min at r.t. with 1 mol % of 16) [48]. However, this of 4-pentynoic4-pentynoic acid in water (89% yieldyield after 30 min at r.t.r.t. with 1 mol %% ofof 1616)[) [48].48]. However,However, thisthis particular catalyst showed a higher reactivity in the eutectic mixture 1ChCl/2Urea (ChCl = choline particularparticular catalystcatalyst showedshowed a higherhigher reactivityreactivity inin thethe eutecticeutectic mixturemixture 1ChCl/2Urea1ChCl/2Urea (ChCl(ChCl == cholinecholine chloride; 99% yield after 15 min under identical reaction conditions) and, consequently, its scope chloride; 99%99% yieldyield after after 15 15 min min under under identical identical reaction reaction conditions) conditions) and, and, consequently, consequently, its scope its scope was was explored only in this alternative and biorenewable reaction medium. exploredwas explored only only in this in alternativethis alternative and biorenewableand biorenewable reaction reaction medium. medium.

Figure 5. Structure of the iminophosphorane-gold(I) complex 16. Figure 5. Structure of the iminophosphorane-gold(I) complex 16.

InIn additionaddition toto palladium,palladium, platinumplatinum andand gold,gold, cheapercheaper coppercopper catalystscatalysts havehave alsoalso beenbeen usedused inin thethe cycloisomerizationcycloisomerization ofof alkynoicalkynoic acidsacids inin aqueousaqueous media.media. Thus,Thus, whilewhile studyingstudying thethe CuBr-catalyzedCuBr-catalyzed cycloaddition of alkynes with azides in t tBuOH/H2O mixtures, Mindt and Schibli observed the cycloaddition of alkynesalkynes withwith azidesazides inin BuOH/HtBuOH/H2OO mixtures, mixtures, Mindt and Schibli observed thethe formationformation ofof enol-lactone enol-lactone by-products by-products when when employing employingγ-alkynoic γ-alkynoic acids asacids substrates, as substrates, so they decidedso they todecided explore to separately explore separately the cyclization the cyclization of these compounds of these compounds [49]. Their [49]. results Their are results shown are in Schemeshown 9in. PerformingScheme 9. Performing the reactions the with reactions 10 mol with % of CuBr10 mol at r.t.,% of different CuBr atγ -alkynoicr.t., different acids γ containing-alkynoic acids both terminalcontaining and both internal terminal C≡C unitsand couldinternal be efﬁcientlyC≡C units transformed could be into efficiently the corresponding transformedγ-alkylidene into the butyrolactones.corresponding γ-alkylidene However, in butyrolactones. some cases, γ -ketoHowever, acids in were some selectively cases, γ-keto obtained acids due were to selectively the rapid hydrolysisobtained due of theto lactonethe rapid products hydrolysis under of the the aqueous lactone conditionsproducts employed.under the aqueous On theother conditions hand, theemployed. attempts On made the other to extend hand, thethe scopeattempts of thismade aqueous to extend protocol the scope to six- of this and aq seven-memberedueous protocol to ring six- enol-lactonesand seven-membered by cyclization ring enol-lactones of 5-hexynoic by acids cyclization and 6-heptynoic of 5-hexynoic acids, respectively,acids and 6-heptynoic failed. It should acids, berespectively, noted, however, failed. thatIt should the former be noted, could however, be cyclizated that the by former carrying could out be the cyclizated reactions by in carrying acetonitrile out the reactions int acetonitrile instead of the tBuOH/H2O mixture. insteadthe reactions of the inBuOH/H acetonitrile2O mixture.instead of the tBuOH/H2O mixture.

Catalysts 2017, 7, 328 10 of 23 Catalysts 2017, 7, 328 10 of 23 Catalysts 2017, 7, 328 10 of 23

Scheme 9. CuBr-catalyzed transformations of different γ-alkynoic acids in aqueous medium. Scheme 9. CuBr-catalyzed transformations of different γ-alkynoic acids in aqueous medium. More recently, CuBr was also employed to promote the cyclization of a variety of More recently, CuBr was also employed to promote the cyclization of a variety of β-hydroxy-γ-alkynoic acids 17 [50]. As shown in Scheme 10, the reactions proceeded cleanly in pure β-hydroxy-γ-alkynoic acids 17 [50].[50]. As As shown shown in Scheme 10,10, the reactions proceeded cleanly in pure water under microwave (MW) irradiation at ◦100 °C, leading to the regio- and stereoselective water underunder microwave microwave (MW) (MW) irradiation irradiation at 100 at C,100 leading °C, leading to the regio-to the and regio- stereoselective and stereoselective formation formation of the five membered ring Z-enol-lactones 18 without observing hydrolysis products. In offormation the ﬁve of membered the five membered ring Z-enol-lactones ring Z-enol-lactones18 without 18 observing without observing hydrolysis hydrolysis products. products. In addition, In addition, the beneficial effect of water was evidenced by the authors, who obtained markedly lower theaddition, beneﬁcial the effectbeneficial of water effect was of evidencedwater was byeviden the authors,ced by the who authors, obtained who markedly obtained lower markedly yields lower when yields when performing the same reactions in classical organic solvents such as THF or acetonitrile. performingyields when theperforming same reactions the same in classicalreactions organicin classi solventscal organic such solvents as THF such or acetonitrile.as THF or acetonitrile. The same The same must be said of the use of MW irradiation, since lower yields were also observed when mustThe same be said must of thebe usesaid of of MW the irradiation,use of MW sinceirradiat lowerion, yieldssince lower were alsoyields observed were also when observed conventional when conventional oil-bath heating or ultrasound irradiation was employed. The process was quite oil-bathconventional heating oil-bath or ultrasound heating irradiationor ultrasound was employed.irradiation Thewas process employed. was quiteThe process general, was tolerating quite general, tolerating a broad range of substitution patterns on the substrate skeleton. However, it ageneral, broad rangetolerating of substitution a broad range patterns of substitution on the substrate patterns skeleton. on the However, substrate it skeleton. should be However, noted that it should be noted that when an alkynoic acid featuring a hydrogen atom and a phenyl group, as the R3 whenshould an be alkynoic noted that acid when featuring an alkynoic a hydrogen acid featuring atom and a a hydrogen phenyl group, atom asand the a phenyl R3 and group, R4 substituents, as the R3 and R4 substituents, was employed in this reaction, the spontaneous dehydration of 18 to form a wasand employedR4 substituents, in this was reaction, employed the spontaneous in this reaction, dehydration the spontaneous of 18 to form dehydration a 5-alkylidene-furan-2-one of 18 to form a 5-alkylidene-furan-2-one product took place. product5-alkylidene-furan-2-one took place. product took place.

Scheme 10. Cu(I)-catalyzed cyclization of β-hydroxy-γ-alkynoic acids in water under microwave Scheme 10.10. Cu(I)-catalyzed cyclization of β-hydroxy-γ-alkynoic-alkynoic acids acids in water underunder microwavemicrowave (MW) irradiation. (MW)(MW) irradiation.irradiation. For its part, the group of Jiao described the cyclization of the propargylic Meldrum´s acids 19 For its part, the group of Jiao described the cyclization of the propargylic Meldrum´s acids 19 into theFor ( itsZ)- part,γ-alkylidene the group butyrolactones of Jiao described 20, in the a basic cyclization aqueous of environment, the propargylic through Meldrum the ´combineds acids 19 into the (Z)-γ-alkylidene butyrolactones 20, in a basic aqueous environment, through the combined intouse of the Cu(OAc) ( )- -alkylidene2 and FeCl butyrolactones3 (Scheme 11) [51]., in a A basic clear aqueous cooperat environment,ive effect of through the two the metals combined was use of Cu(OAc)2 and FeCl3 (Scheme 11) [51]. A clear cooperative effect of the two metals was useobserved, of Cu(OAc) the yields2 and decreasing FeCl3 (Scheme drastically 11)[ 51when]. A Cu(OAc) clear cooperative2 or FeCl3 was effect used of theas the two sole metals catalyst. was observed, the yields decreasing drastically when Cu(OAc)2 or FeCl3 was used as the sole catalyst. observed,The process the most yields probably decreasing involves drastically the in situ when generation Cu(OAc) of2 aor γ-alkynoic FeCl3 was acid used intermediate as the sole through catalyst. The process most probably involves the in situ generation of a γ-alkynoic acid intermediate through Thea hydrolysis/decarboxylation process most probably involves sequence. the inOn situ the generation other hand, of aalthoughγ-alkynoic the acid mechanism intermediate could through not be a hydrolysis/decarboxylation sequence. On the other hand, although the mechanism could not be aunambiguously hydrolysis/decarboxylation established, it was sequence. assumed On that the the other Cu2+ hand,ion is the although one responsible the mechanism for the couldactivation not unambiguously established, it was assumed that the Cu2+ ion is2+ the one responsible for the activation beof the unambiguously alkyne unit established,during the fina it wasl cycloisomerization assumed that the step, Cu withion isFe the3+ probably one responsible facilitating for the of the alkyne unit during the final cycloisomerization step, with Fe3+ probably3+ facilitating the activationintramolecular of the nucleophilic alkyne unit duringaddition the of ﬁnal the cycloisomerizationcarboxylate on thestep, C≡C withbond Fe by probablycoordination facilitating to the intramolecular nucleophilic addition of the carboxylate on the C≡C bond by coordination to the thecarbonyl intramolecular group. nucleophilic addition of the carboxylate on the C≡C bond by coordination to the carbonyl group.

Catalysts 20172017,, 77,, 328328 11 of 23 Catalysts 2017, 7, 328 11 of 23

SchemeScheme 11. 11.Cu/Fe-cocatalyzed Cu/Fe-cocatalyzed synthesis of of lactones lactones from from propargylic propargylic Meldrum’s Meldrum’s acids. acids. Scheme 11. Cu/Fe-cocatalyzed synthesis of lactones from propargylic Meldrum’s acids. Further studies by the same group showed that the same catalytic reactions can be more Further studies by the same group showed that the same catalytic reactions can be more conveniently carried out employing AgNO3 (5 mol %) instead of the Cu/Fe system [52]. The conveniently carriedcarried out out employing employing AgNO AgNO3 (53 mol (5 %)mol instead %) instead of the Cu/Feof the systemCu/Fe [52system]. The [52]. reactions, The reactions, performed at 100 °C in a H2O/DMF (N,N-dimethylformamide) mixture under air, afforded performed at 100 ◦C in a H O/DMF (N,N-dimethylformamide) mixture under air, afforded regio- and reactions,regio- and performed stereoselectively at 1002 °C the in ( aZ )-Hγ2-alkylideneO/DMF (N,N-dimethylformamide) butyrolactone products 20 mixture in 45–87% under isolated air, affordedyields stereoselectively the (Z)-γ-alkylidene butyrolactone products 20 in 45–87% isolated yields after ca. 1 h. regio-after and ca. stereoselectively1 h. Remarkably, the no (co-catalystsZ)-γ-alkylidene or base butyrolactones were in this products case needed. 20 in 45–87% On the isolatedother hand, yields Remarkably, no co-catalysts or bases were in this case needed. On the other hand, transformation of aftertransformation ca. 1 h. Remarkably, of the related no co-catalysts Meldrum´s or acids base s21 were into inlactones this case 22 ,needed. containing On thean all-carbonother hand, 21 22 thetransformationquaternary related Meldrum center of the ´ats acids therelated C-4 intoposition,Meldrum´s lactones was acidsalso, containing described21 into an lactonesby all-carbon Ahmar 22 and quaternary, containing Fillion using center an catalyticall-carbon at the C-4 position, was also described by Ahmar and Fillion using catalytic amounts of Ag CO , and mixtures quaternaryamounts ofcenter Ag2CO at3 , theand C-4mixtures position, THF/H was2O oralso toluene/H described2O asby the Ahmar reaction and media Fillion2 (Scheme 3using 12) catalytic [53]. THF/HamountsAgain,2O ofthe orAg 5- toluene/H2COexo-3dig, and cyclization 2mixturesO as the products reactionTHF/H2O mediawere or toluene/H exclusively (Scheme2O 12 asformed)[ the53]. reaction Again,and the themedia reactions 5-exo (Scheme-dig proceededcyclization 12) [53]. productsAgain,cleanly thewere in 5-theexo exclusively absence-dig cyclization of formed base. However, andproducts the reactions wewere must exclusively proceeded note that mixtures cleanlyformed in ofand the E/Z absencethe isomers reactions of were base. proceeded in However, most wecleanlycases must inobtained note the thatabsence starting mixtures of from base. of thoseE/Z However,isomers substrates we were containingmust in most note cases anthat internal obtainedmixtures C≡C starting ofbond. E/Z isomers from those were substrates in most containingcases obtained an internal starting C from≡C bond.those substrates containing an internal C≡C bond.

Scheme 12. Silver-catalyzed cyclization of the propargylic Meldrum’s acids. Scheme 12. Silver-catalyzed cyclization of the propargylic Meldrum’s acids. 2.2. Tandem andScheme Cascade 12. Processes Silver-catalyzed Involving cyclization the Cycloisomerization of the propargylic of an Alkynoic Meldrum’s Acid acids.

2.2. Tandem The aminolysis andand CascadeCascade of ProcessesProcesses lactones InvolvingisInvolving a common thethe CycloisomerizationtransformationCycloisomerization in organic ofof anan AlkynoicAlkynoic synthesis AcidAcid which allows their direct conversion into linear amides [54,55]. The combination of this reaction with the cycloisomerizationThe aminolysis aminolysis ofof of lactonesalkynoic lactones isacids isa common a has common been transformation extensiv transformationely studied in organic in in organicthe lastsynthesis years synthesis givingwhich which access allows allowsto their a theirdirecthuge direct conversionnumber conversion of nitrogen-containinginto intolinear linear amides amides heterocyclic [54,55]. [54,55 compounds,].The The combination combination through differentof ofthis this cascadereaction reaction processes, with with the cycloisomerizationby appropriate selection of alkynoic of the acids functionalized has been extensivelyextensiv amineely partner studied [56–59]. in the lastIn this years context, giving accessLiu and to a huge numbernumber ofof nitrogen-containingnitrogen-containing heterocyclic heterocyclic compounds, compounds, through through different different cascade cascade processes, processes, by by appropriate selection of the functionalized amine partner [56–59]. In this context, Liu and

Catalysts 2017, 7, 328 12 of 23 Catalysts 2017, 7, 328 12 of 23 Catalysts 2017, 7, 328 12 of 23 co-workers developed an efficient and broad scope gold-catalyzed reaction for the synthesis of fused co-workersappropriate developed selection of an the efficient functionalized and broad amine scope partner gold-catalyzed [56–59]. In reaction this context, for the Liu synthesis and co-workers of fused polycyclic indoles 23 in water, starting from 2-(1H-indol-1-yl)alkylamines and alkynoic acids polycyclicdeveloped indoles an efﬁcient 23 andin water, broad scopestarting gold-catalyzed from 2-(1H-indol-1-yl)alkylamines reaction for the synthesis and of fusedalkynoic polycyclic acids (Scheme 13) [60]. (Schemeindoles 23 13)in [60]. water, starting from 2-(1H-indol-1-yl)alkylamines and alkynoic acids (Scheme 13)[60].

Scheme 13. Gold-catalyzed synthesis of fused polycyclic indoles in water. SchemeScheme 13. 13. Gold-catalyzedGold-catalyzed synthesis synthesis of of fused fused polycyclic polycyclic indoles indoles in in water. water. The process involves the aminolysis of the in situ formed enol-lactones E to generate the linear The process involves the aminolysis of the in situ formed enol-lactones E to generate the linear keto-amidesThe process F, which involves subsequently the aminolysis evolve of theinto in G situ via formed a gold-catalyzed enol-lactones NE-acyliminiumto generate theion keto-amides F, which subsequently evolve into G via a gold-catalyzed N-acyliminium ion linearformation/cyclization. keto-amides F, whichFinal intramolecular subsequently evolvenucleoph intoilicG attackvia a of gold-catalyzed the C-2 carbonN of-acyliminium the indolic unit ion formation/cyclization. Final intramolecular nucleophilic attack of the C-2 carbon of the indolic unit formation/cyclization.to the iminium carbon Final yields intramolecular the products nucleophilic 23. To facilitate attack the of thecyclization C-2 carbon step of leading the indolic to unitG, the to to the iminium carbon yields the products 23. To facilitate the cyclization step leading to G, the theaddition iminium trifluoroactic carbon yields acid the wa productss in some23. Tocases facilitate required. the cyclizationAs shown step in Scheme leading to13,G ,the the reactions addition addition trifluoroactic acid was in some cases required. As shown in Scheme 13, the reactions triﬂuoroacticproceeded in acid short was times in some under cases microwave required. Asirradiat shownion, in Schemetolerating 13 ,the the reactionspresence proceededof different in proceeded in short times under microwave irradiation, tolerating the presence of different shortfunctional times groups. undermicrowave irradiation, tolerating the presence of different functional groups. functional groups. The same groupgroup alsoalso describeddescribed the the coupling coupling of of 4-pentynoic 4-pentynoic acid acid with witho-aminophenylmethanol o-aminophenylmethanol in waterThe catalyzed same group by the also cationic described gold(I) the complex coupling [Au{P oft Bu4-pentynoic(o-biphenyl)}(MeCN)][SbF acid with o-aminophenylmethanol] (Scheme 14)[61]. in water catalyzed by the cationic gold(I) complex [Au{P2 tBu2(o-biphenyl)}(MeCN)][SbF6 6] (Scheme in water catalyzed by the cationic gold(I) complex [Au{PtBu2(o-biphenyl)}(MeCN)][SbF6] (Scheme The14) [61]. reaction The reaction afforded afforded the pyrrolo[2,1- the pyrrolo[2,1-b]benzo[db][1,3]oxazin-1-one]benzo[d][1,3]oxazin-1-one24 in 50% 24 yield. in 50% However, yield. However, we must 14) [61]. The reaction afforded the pyrrolo[2,1-b]benzo[d][1,3]oxazin-1-one 24 in 50% yield. However, notewe must that thisnote valuethat this was value much was lower much to that lower obtained to that in obtained THF under in THF identical under reaction identical conditions reaction we must note that this value was much lower to that obtained in THF under identical reaction (91%conditions yield), (91% so it yield), is not surprisingso it is not that surprising the generality that the of generality the process of was the studiedprocess inwas the studied latter solvent. in the conditions (91% yield), so it is not surprising that the generality of the process was studied in the Aslatter in solvent. the precedent As in case,the precedent the reaction case, is the initiated reaction by is the initiated cycloisomerization by the cycloisomerization of the alkynoic of acid, the latter solvent. As in the precedent case, the reaction is initiated by the cycloisomerization of the subsequentalkynoic acid, aminolysis subsequent of theaminolysis enol lactone of the intermediate, enol lactone andintermediate, ﬁnal cyclization and final of thecyclization resulting of keto the alkynoic acid, subsequent aminolysis of the enol lactone intermediate, and final cyclization of the amideresulting catalyzed keto amide by the catalyzed gold complex. by the gold complex. resulting keto amide catalyzed by the gold complex.

Scheme 14. Gold-catalyzed synthesis of the pyrrolo[2,1- b]benzo[d][1,3]oxazin-1-one 24 in water. Scheme 14. Gold-catalyzed synthesis of the pyrrolo[2,1-b]benzo[d][1,3]oxazin-1-one 24 in water.

Catalysts 2017, 7, 328 13 of 23 Catalysts 2017, 7, 328 13 of 23 Catalysts 2017, 7, 328 13 of 23 In another vein, the group of Jiang developed an aqueous protocol for the one-pot synthesis of phthalidesIn another 26 from vein, terminalterminal the group alkynes of Jiang and developed o-iodobenzoic-iodobenzoic an aqueous acid (Scheme protocol 1515)for)[ the[62].62 ].one-pot The process, synthesis which of phthalides 26 from terminal alkynes and o-iodobenzoic acid (Scheme 15) [62]. The process, which involves the initial Sonogashira coupling of thethe substrates and subsequent stereoselective 5-exo-dig involves the initial Sonogashira coupling of the substrates and subsequent stereoselective 5-exo-dig cyclization of the resulting ethynyl-benzoic acid intermediates 25, was catalyzed by palladium cyclization of the resulting ethynyl-benzoic acid intermediates 25, was catalyzed by palladium immobilized on on carbon carbon nanotubes nanotubes (CNTs) (CNTs) in in a aDMF:H DMF:H2O2 Omixture. mixture. Unlike Unlike previous previous examples examples of this of immobilized on carbon nanotubes (CNTs) in a DMF:H2O mixture. Unlike previous examples of this tandemthis tandem reaction, reaction, formation formation of isocoumarin of isocoumarin by-products by-products (6-endo (6-endo-dig -cyclization)dig cyclization) was wasin this in thiscasecase not tandem reaction, formation of isocoumarin by-products (6-endo-dig cyclization) was in this case not observed,not observed, and andno additives no additives such such as phosphine as phosphine ligands ligands or CuI or CuIwere were needed. needed. observed, and no additives such as phosphine ligands or CuI were needed.

Scheme 15. Catalytic synthesis of phthalides from terminal alkynes and o-iodobenzoic acid. Scheme 15. CatalyticCatalytic synthesis synthesis of phthalides from terminal alkynes and o-iodobenzoic acid. Taking advantage of the ability of the dinuclear iminophosphorane-palladium(II) complex 4 to Taking advantage of the ability of the dinucleardinuclear iminophosphorane-palladium(II) complex 4 to promote the fast and selective transformation of bispropargylic carboxylic acids 5 into enol-lactones promote the fast and selective transformation of bispropargylic carboxylic acids 5 into enol-lactones promote6 (Scheme the fast 4), andGarcía-Álvarez selective transformation and co-workers of bispropargylic could set up carboxylican unprecedented acids 5 into one-pot enol-lactones tandem 6 6 (Scheme 4), García-Álvarez and co-workers could set up an unprecedented one-pot tandem (Schemeprocess4), combining Garc ía-Á thelvarez aforementioned and co-workers reaction could with set a up copper-catalyzed an unprecedented 1,3-dipolar one-pot cycloaddition tandem process of processcombiningazides combining with the the aforementioned terminal the aforementioned alkyne reaction arm of reaction withthe enol-l a copper-catalyzedwithactone a copper-catalyzed products 1,3-dipolar(Scheme 1,3-dipolar 16) cycloaddition [30]. To cycloaddition promote of azides the of azides with the terminal alkyne arm of the enol-lactone products2 (Scheme 16) [30]. To promote the with1,3-dipolar the terminal cycloaddition alkyne arm step of thethe enol-lactonepolymeric Cu(I) products catalyst (Scheme [Cu{µ -16N,S)[-(PTA)=NP(=S)(OEt)30]. To promote the2}] 1,3-dipolarx[SbF6]x 2 2 1,3-dipolarcycloaddition(27) containing cycloaddition step the the same polymericstep hydrophilic the polymeric Cu(I) iminophospho catalyst Cu(I) catalyst [Cu{raneµ -[Cu{ N,Sligand-(PTA)=NP(=S)(OEt)µ -N,S [63],-(PTA)=NP(=S)(OEt) in combination2}]x[SbF with2}]6x[SbF] xthe(27 6]x) (containing272,6-lutidine) containing the base, same the hydrophilicwassame employed. hydrophilic iminophosphorane The iminophospho tandem process ligandrane proceeded [ 63ligand], in combination [63], in purein combination water with theunder 2,6-lutidine with mild the 2,6-lutidinebase,conditions, was employed. base, affording was The theemployed. tandem bicyclic processtriazol-enol-lactones The tandem proceeded process in 28 pure in proceededexcellent water under yields in mild pureafter conditions, a watersimple underextraction affording mild conditions,thewith bicyclic diethyl affording triazol-enol-lactones ether (no the chromatogr bicyclic triazol-enol-lactones28aphicin excellent purification yields was 28 after needed).in excellent a simple yields extraction after a with simple diethyl extraction ether with(no chromatographic diethyl ether (no puriﬁcation chromatogr wasaphic needed). purification was needed).

Scheme 16. Access to bicyclic triazol-enol-lactones from of bispropargylic carboxylic acids Schemeand azides. 16. Access to bicyclic triazol-enol-lactones from of bispropargylic carboxylic acids and azides. Scheme 16. Access to bicyclic triazol-enol-lactones from of bispropargylic carboxylic acids andOn azides. the other hand, based on the capability of copper salts to promote the conjugate alkynylationOn the other of hand, electron-deficient based on the capabilityolefins, the of copper(Z)-γ-alkylidene salts to promote butyrolactones the conjugate 30 alkynylationcould be of electron-deﬁcientsynthesizedOn the other in a oleﬁns,hand,one-pot based themanner (Z )-onγ -alkylidene startingthe capability from butyrolactones the of correspondingcopper30 saltscould terminalto be promote synthesized alkynes the in andconjugate a one-pot the alkynylationmanner5-alkylidene-Meldrun’s starting of fromelectron-deficient the acids corresponding 29, via olefins, in situ terminal formationthe alkynes(Z)- γof-alkylidene the and corresponding the 5-alkylidene-Meldrun’s butyrolactones propargylic 30 Meldrun’s could acids 29be , synthesizedvia in situ formation in a one-pot of the manner corresponding starting propargylic from the Meldrun’scorresponding acids terminal (Scheme alkynes17). The and process the 5-alkylidene-Meldrun’s acids 29, via in situ formation of the corresponding propargylic Meldrun’s

Catalysts 2017, 7, 328 14 of 23 Catalysts 2017, 7, 328 14 of 23 Catalysts 2017, 7, 328 14 of 23 wasacids promoted (Scheme by 17). the The Cu(OAc) process2/FeCl was promoted3 combination by the discussed Cu(OAc) above2/FeCl3for combination the cyclization discussed of Meldrun above ´s acids (Scheme 17). The process was promoted by the Cu(OAc)2/FeCl3 combination discussed above acidsfor 19the(Scheme cyclization 11 )[of51 Meldrun´s]. acids 19 (Scheme 11) [51]. for the cyclization of Meldrun´s acids 19 (Scheme 11) [51].

SchemeScheme 17. 17.Cu/Fe-cocatalyzed Cu/Fe-cocatalyzed synthesissynthesis of lactones from from alkynes alkynes and and 5-alkylidene-Meldrum’s 5-alkylidene-Meldrum’s acids. acids. Scheme 17. Cu/Fe-cocatalyzed synthesis of lactones from alkynes and 5-alkylidene-Meldrum’s acids. Finally, the combination of metal catalysis and biocatalysis has emerged in recent years as a Finally,Finally, the the combination combination of of metal metal catalysiscatalysis and biocatalysis has has emerged emerged in in recent recent years years as asa a powerful tool for developing new synthetic methodologies merging the advantages of both powerfulpowerful tool tool for developingfor developing new syntheticnew synthetic methodologies methodologies merging merging the advantages the advantages of both disciplinesof both disciplines in terms of reaction scope and selectivity [64–66]. In this context, García-Álvarez, indisciplines terms of reaction in terms scope of reaction and selectivity scope and [64– 66selectivity]. In this [64–66]. context, In Garc thisí a-context,Álvarez, García-Álvarez, González-Sab ín González-Sabín and co-workers described very recently the one-pot conversion of 4-pentynoic acid andGonzález-Sabín co-workers described and co-workers very recently described the very one-pot rece conversionntly the one-pot of 4-pentynoic conversion acidof 4-pentynoic into enantiopure acid into enantiopure γ-hydroxyvaleric acid in aqueous medium, through the combined use of KAuCl4 γ-hydroxyvalericinto enantiopure acid γ-hydroxyvaleric in aqueous medium, acid in throughaqueous themedium, combined through use ofthe KAuCl combinedand use ketoreductases of KAuCl4 and ketoreductases (KREDs) (Scheme 18) [67]. The process involves the initial4 gold-catalyzed (KREDs)and ketoreductases (Scheme 18)[ (KREDs)67]. The process(Scheme involves 18) [67]. the The initial process gold-catalyzed involves the cycloisomerization initial gold-catalyzed of the cycloisomerization of the substrate, concomitant hydrolysis of the lactone to form levulinic acid, and substrate,cycloisomerization concomitant of hydrolysisthe substrate, of concomitant the lactone tohydrolysis form levulinic of the lactone acid, and to form ﬁnal levulinic bioreduction acid, and of the final bioreduction of the keto group of the latter. Remarkably, no isolation or purification steps were final bioreduction of the keto group of the latter. Remarkably, no isolation or purification steps were ketorequired, group the ofthe reaction latter. medium Remarkably, coming no from isolation the meta orl-catalyzed puriﬁcation reaction steps being were directly required, employed the reaction in required, the reaction medium coming from the metal-catalyzed reaction being directly employed in mediumthe enzymatic coming fromstep. the Also metal-catalyzed of note is the reaction fact th beingat, just directly by selecting employed the in adequate the enzymatic KRED, step. both Also the enzymatic step. Also of note is the fact that, just by selecting the adequate KRED, both ofenantiomers note is the fact of the that, γ-hydroxyvaleric just by selecting acid the adequatecould be obtained KRED, both with enantiomersexcellent ee values. of the γ-hydroxyvaleric acidenantiomers could be obtained of the γ-hydroxyvaleric with excellent eeacidvalues. could be obtained with excellent ee values.

Scheme 18. Chemoenzymatic one-pot conversion of 4-pentynoic acid into enantiopure SchemeScheme 18. 18. Chemoenzymatic one-pot one-pot conversion conversion of of 4-pentynoic 4-pentynoic acid acid into into enantiopure enantiopure γ-hydroxyvaleric acid. γ-hydroxyvalericγ-hydroxyvaleric acid. acid.

Catalysts 2017, 7, 328 15 of 23 Catalysts 2017, 7, 328 15 of 23

3. Intermolecular Processes

3.1. Catalytic Addition of Carboxylic Acids to Terminal andand InternalInternal AlkynesAlkynes Although the intermolecular hydro-oxycarbonylationhydro-oxycarbonylation of alkynes has been widely studied in organic media [[1–6],1–6], to date there are very few examplesexamples of this catalytic transformation described in water. InIn this regard, Cadierno,Cadierno, GimenoGimeno andand co-workersco-workers evaluated in 2011 the catalytic potential of a 3 3 3 3 diverse familyfamily ofof ruthenium(IV)ruthenium(IV) complexes, complexes, of of general general composition compositiontrans trans-[RuCl-[RuCl2(η2(η:η:η-C-C1010HH1616)(L)])(L)] ((31a–ss inin FigureFigure6 6),), for for the the hydro-oxycarbonylation hydro-oxycarbonylation of of terminal terminal alkynes alkynes in in aqueous aqueous medium medium [ 68[68].].

Figure 6. Structure of the bis(allyl)-ruthenium(IV) complexes 31a–s..

All thesethese compounds compounds were were found found to beto activebe active catalysts catalysts in the in addition the addition of benzoic of acidbenzoic to 1-hexyne acid to 1-hexyne in pure water, providing the corresponding enoln esters nBuC(OBz)=CH2 (Markovnikov in pure water, providing the corresponding enol esters BuC(OBz)=CH2 (Markovnikov addition n product)addition product) and (E/Z and)-nBuCH=CH(OBz) (E/Z)- BuCH=CH(OBz) (anti-Markovnikov (anti-Markovnikov addition addition products) products) in moderate in moderate to good to yieldsgood yields after 3–24after h 3–24 of heating h of heating at 60 ◦ Cat (with60 °C a (with Ru loading a Ru loading of 2 mol of %). 2 mol A high %). selectivityA high selectivity towards thetowards Markovnikov the Markovnikov addition addition product product was in general was in observed,general observed, except inexcept the case in the of catalystscase of catalysts31m–p containing31m–p containing a labile amine a labile or nitrile amine ligand or which nitrile generated ligand preferentially which generated (E/Z)-nBuCH=CH(OBz), preferentially n albeit(E/Z)- onlyBuCH=CH(OBz), in moderate yields. albeit Theonly best in resultsmoderate in termsyields. of The activity best and results regioselectivity in terms of were activity obtained and regioselectivity3 were3 obtained with [RuCl2(η3:η3-C10H16)(PPh3)] (31a), which was ablen to generate the with [RuCl2(η :η -C10H16)(PPh3)] (31a), which was able to generate the enol ester BuC(OBz)=CH2 n inenol 96% ester yield BuC(OBz)=CH (by gas chromatography)2 in 96% yield after(by gas only chromatography) 3 h of heating. after However, only 3 from h of heating. the data However, obtained, nofrom relationships the data obtained, between no the relationships steric and/or between electronic the nature steric ofand/or the auxiliary electronic ligand nature L and of the the auxiliary catalytic activityligand L observed and the couldcatalytic be activity drawn. observed On the other could hand, be drawn. it must On be the also other highlighted hand, it that,must with be also the highlighted that, with3 3 the exception of [RuCl2(η3:η3-C10H16)(TPPMS)] (31b; TPPMS = exception of [RuCl2(η :η -C10H16)(TPPMS)] (31b; TPPMS = 3-(diphenylphosphino)benzenesulfonate 3-(diphenylphosphino)benzenesulf3 3 onate sodium salt) and [RuCl2(η3:η3-C10i H16){P(OR)3}] (R = Me sodium salt) and [RuCl2(η :η -C10H16){P(OR)3}] (R = Me (31i), Et (31j), Pr (31k)), these Ru(IV) i complexes(31i), Et (31j are), Pr completely (31k)), these insoluble Ru(IV) incomplexes water.Accordingly, are completely in insoluble most of thein water. reactions Accordingly, the catalyst in remainedmost of the dissolved reactions inthe the catalyst organic remained phase, formingdissolved an in emulsion the organic with phase, water forming under an stirring. emulsion In other with words,water under the reactions stirring. proceeded In other under words, the the so-called reactions “on-water” proceeded conditions under [the69, 70so-called]. In addition, “on-water” when theconditions same reactions [69,70]. were In addition, carried out when under the homogeneous same reactions conditions were carried using organic out under solvents, homogeneous the results wereconditions much worseusing in organic terms of yieldssolvents, (the regioselectivitythe results were remained much unaffected), worse in pointingterms of out yields the marked (the positiveregioselectivity effect of remained water in the unaffected), process. Although pointing to out a lesser the extent,marked the positive beneﬁcial effect effect of ofwater water in in the catalyticprocess. additionAlthough of to carboxylic a lesser acidsextent, to terminalthe beneficial alkynes effect promoted of water by tetheredin the catalytic arene-ruthenium(II) addition of complexescarboxylic acids was alsoto terminal observed alkynes by Demonceau promoted by and tethered co-workers, arene-ruthenium(II) who obtained highercomplexes yields was when also performingobserved by the Demonceau reactions in moistand co-workers, vs. dry toluene who [71 obtained]. higher yields when performing the reactions in moist vs. dry toluene [71]. 3 3 The most active catalyst of the series, i.e., [RuCl2(η :η -C10H16)(PPh3)] (31a), showed also a wide 3 3 scopeThe allowing most active the preparation catalyst of of the a largeseries, variety i.e., [RuCl of enol2(η esters:η -C1032H16by)(PPh selective3)] (31a Markovnikov), showed also addition a wide ofscope different allowing carboxylic the preparation acids to both of a large aliphatic variety and of aromatic enol esters terminal 32 by alkynes,selectiveas Markovnikov well as to 1,3-enynes addition (Schemeof different 19 )[carboxylic68,72,73]. acids As a to general both aliphatic trend, the and reactions aromatic proceeded terminal alkynes, faster, andas well with as higherto 1,3-enynes yields, when(Scheme aliphatic 19) [68,72,73]. terminal As alkynes a general were trend, employed the re asactions substrates. proceeded Also notablefaster, and are thewith high higher functional yields, groupwhen aliphatic compatibility terminal showed alkynes by complex were employed31a and theas substrates. absence of Also competing notable processes are the high of hydration functional of thegroup alkynes. compatibility showed by complex 31a and the absence of competing processes of hydration of the alkynes.

CatalystsCatalysts 20172017,, 77,, 328328 1616 ofof 2323

Scheme 19. Ruthenium(IV)-catalyzed Markovnikov addition of carboxylic acids to terminal alkynes. Scheme 19. Ruthenium(IV)-catalyzed Markovnikov addition of carboxylic acids to terminal alkynes.

3 3 33 Further evidenceevidence ofof thethe versatilityversatility ofof[RuCl [RuCl2(2η(η:3η:η3-C-C1010H1616)(PPh)(PPh3)]3)] ( (31a31a)) was was gained gained in thethe reactionsreactions ofof the the terminal terminal diynes diynes33 with 33 benzoicwith benzoic acid. Thus, acid. as shownThus, inas Schemeshown 20 in, theScheme corresponding 20, the enynescorresponding34 or theenynes diesters 34 or35 thecould diesters be selectively 35 could synthesizedbe selectively with synthesized31a just bywith adjusting 31a just theby diyne/benzoicadjusting the diyne/benzoic acid ratio employed acid ratio [68 employed,72,73]. [68,72,73].

Scheme 20. Ruthenium(IV)-catalyzed Markovnikov addition of benzoic acid to terminal diynes. Scheme 20. Ruthenium(IV)-catalyzed Markovnikov addition of benzoic acid to terminal diynes.

The only limitation encounteredencountered withwith thethe rutheniumruthenium catalystcatalyst 31a31a isis thatthat itit isis completelycompletely inactiveinactive withwith internalinternal alkynes;alkynes; substrates which, as commentedcommented in the introduction of this article,article, show aa muchmuch lowerlower reactivityreactivity inin thesethese intermolecularintermolecular hydrocarboxylationhydrocarboxylation reactions.reactions. ForFor thisthis particularparticular classclass ofof alkynes,alkynes, Cadierno,Cadierno, GarcGarcía-Garridoía-Garrido and co-workersco-workers developed very recently a protocol in waterwater employing the catalytic system [AuCl(PPh )]/AgOAc [74]. Thus, as depicted in Scheme 21, a broad employing the catalytic system [AuCl(PPh33)]/AgOAc [74]. Thus, as depicted in Scheme 21, a broad rangerange ofof trisubstitutedtrisubstituted enol esters 36 couldcould bebe synthetizedsynthetized in goodgood yieldsyields byby additionaddition ofof differentdifferent aromatic,aromatic, aliphatic,aliphatic, heterocyclic heterocyclic and αand,β-unsaturated α,β-unsaturated carboxylic carboxylic acids to internalacids alkynesto internal symmetrically alkynes substitutedsymmetrically with substi aliphatictuted groups.with aliphatic Concerning groups. the Concerning use of aromatic the use alkynes, of aromatic they showed alkynes, only they a residualshowed reactivityonly a residual towards reactivity benzoic acidtowards and, benzoic when an acid aliphatic and, carboxylicwhen an aliphatic acid was carboxylic employed, acid a higher was temperatureemployed, a andhigher catalyst temperature loading wereand catalyst required load to obtaining were the required corresponding to obtain products the corresponding in moderate yields.products Interestingly, in moderate compounds yields. Interestingly,36 were obtained compounds in a stereoselective 36 were obtained manner in a stereoselective (only Z isomers) manner as the result(only Z of isomers) the exclusive as theanti resultaddition of theof exclusive the O-H anti bond addition of thecarboxylic of the O-H acid bond to of the the alkyne. carboxylic acid to the alkyne.

Catalysts 2017, 7, 328 17 of 23 Catalysts 2017, 7, 328 17 of 23 Catalysts 2017, 7, 328 17 of 23

Scheme 21. Gold-catalyzed addition of carboxylic acids to symmetrically substituted Schemeinternal 21.alkynes.21.Gold-catalyzed Gold-catalyzed addition addition of carboxylic of carboxylic acids to symmetrically acids to substitutedsymmetrically internal substituted alkynes. internal alkynes. The reactivity of some unsymmetrically substituted internal alkynes towards benzoic acid in The reactivity of some unsymmetrically substituted internal alkynes towards benzoic acid in water was also explored using the catalytic system [AuCl(PPh3)]/AgOAc, the reations leading in waterThe was reactivity also explored of some using unsymmetrically the catalytic system substitu [AuCl(PPhted internal)]/AgOAc, alkynes the towards reations benzoic leading inacid most in most of the cases to mixtures of regioisomers derived from the3 attack of acid to both carbon atoms of ofwater the caseswas also to mixtures explored of using regioisomers the catalytic derived system from [AuCl(PPh the attack of3)]/AgOAc, acid to both the carbonreations atoms leading of the in the alkyne (complete Z-selectivity was again observed for both regioisomers). Only when the alkynemost of (complete the cases toZ-selectivity mixtures of was regioisomers again observed derive ford from both the regioisomers). attack of acid Only to both when carbon the activated atoms of activated internal alkynes 37 and 38 were employed as substrates a complete regioselectivity to enol internalthe alkyne alkynes (complete37 and Z38-selectivitywere employed was again as substrates observed a completefor both regioselectivityregioisomers). toOnly enol when esters the39 esters 39 and 40, respectively, was observed (Scheme 22) [74]. andactivated40, respectively, internal alkynes was observed 37 and 38 (Scheme were employed 22)[74]. as substrates a complete regioselectivity to enol esters 39 and 40, respectively, was observed (Scheme 22) [74].

Scheme 22. Regio- and stereoselective addition of benzoic acid to unsymmetrically substituted alkynes. Scheme 22. Regio- and stereoselective addition of benzoic acid to unsymmetrically substituted alkynes. 3.2. CatalyticScheme Addition22. Regio- of Carboxylic and stereoselective Acids to Terminal addition Propargylic of benzoic Alcohols acid to unsymmetrically substituted alkynes. 3.2. Catalyticβ-Oxo esters Addition are of useful Carboxylic intermediates Acids to Terminal in organic Propargylic chemistry. Alcohols For example, they have been employed3.2. Catalyticβ-Oxo inesters Addition the synthesisare of usefulCarboxylic of intermediates different Acids to pharmaceuticals Terminal in orga Propargylicnic chemistry. [75– Alcohols77], andFor canexample, be easily they transformed have been into the corresponding α-hydroxy ketones, which are structural units present in a large variety of employedβ-Oxo inesters the synthesis are useful of differentintermediates pharmaceut in orgaicalsnic [75–77],chemistry. and Forcan example,be easily transformedthey have been into biologically active molecules [78,79]. Among the different synthetic approaches to β-oxo esters [80], employedthe corresponding in the synthesis α-hydroxy of different ketones, pharmaceut which areicals structural [75–77], units and canpresent be easily in a transformedlarge variety into of the ruthenium-catalyzed addition of carboxylic acids to terminal propargylic alcohols has emerged thebiologically corresponding active moleculeα-hydroxys [78,79]. ketones, Among which the are differen structuralt synthetic units approaches present in toa βlarge-oxo estersvariety [80], of as one of the most straightforward and atom-economical routes (Scheme 23). The process involves biologicallythe ruthenium-catalyzed active molecule additions [78,79]. of Amongcarboxylic the acids differen to terminalt synthetic propargylic approaches alcohols to β-oxo has esters emerged [80], the ruthenium-catalyzed addition of carboxylic acids to terminal propargylic alcohols has emerged

Catalysts 2017, 7, 328 18 of 23 Catalysts 2017, 7, 328 18 of 23 as one of the most straightforward and atom-economical routes (Scheme 23). The process involves thethe Markovnikov attackattack ofof the carboxylic acid to an initially formed π-alkyne-ruthenium-alkyne-ruthenium complex complex H,, whichwhich isis followedfollowed byby thethe intramolecularintramolecular transesteriﬁcationtransesterification of the resulting intermediate II toto form anan alkenyl derivative J. TheThe ﬁnalfinal protonolysisprotonolysis ofof JJ releasesreleases thethe ββ-oxo-oxo esterester productproduct andand regeneratesregenerates thethe catalytically activeactive rutheniumruthenium species.species.

Scheme 23. Mechanism of the Ru-catalyzed β-oxo esters formation reactions.

Since thethe pioneering pioneering work work by by Mitsudo Mitsudo and and Watanabe Watanabe in 1987 in [811987], a number[81], a number of ruthenium of ruthenium catalysts forcatalysts this transformation for this transformation have been developed have [been80,82 ].developed Among them, [80,82]. the bis(allyl)-ruthenium(IV)Among them, the 3 3 bis(allyl)-ruthenium(IV)3 3 complex [RuCl2(η3:η3-C10H16)(PPh3)] (31a) (Figure 6) proved to be active in complexbis(allyl)-ruthenium(IV) [RuCl2(η :η -C10 complexH16)(PPh [RuCl3)] (31a()η (Figure:η -C H6) proved)(PPh )] to ( be31a active) (Figure in water 6) proved [ 68]. Thus,to be asactive shown in inwater Scheme [68]. 24 Thus,, starting as shown from different in Scheme propargylic 24, starting alcohols from anddifferent benzoic propargylic acid, a family alcohols of β-oxo and estersbenzoic41 couldacid, a befamily synthetized of β-oxo inesters moderate 41 could to be good synthetized yields employing in moderate identical to good experimental yields employing conditions identical to thoseexperimental applied inconditions the preparation to those of theapplied enol estersin the32 preparation(Scheme 19 ).of Although the enol theesters scope 32 of (Scheme the reaction 19). concerningAlthough the the scope carboxylic of the acid reaction partner concerning was not studied the carboxylic in much acid detail, partner the authors was not showed studied that in it much is not restricteddetail, the to benzoicauthors acidshowed since thethat addition it is ofnot 2-chlorobenzoic restricted to acid,benzoic pentaﬂuorobenzoic acid since the acid, addition heptanoic of acid2-chlorobenzoic and 3-cyclopentylpropionic acid, pentafluorobenzoic acid to 1-phenyl-2-propyn-1-ol acid, heptanoic acid also and afforded 3-cyclopentylpropionic the corresponding acidβ-oxo to esters1-phenyl-2-propyn-1-ol in 47–90% yield. also afforded the corresponding β-oxo esters in 47–90% yield.

Scheme 24. Synthesis of β-oxo esters in water catalyze catalyzedd by the ruthenium(IV) complex 31a..

Catalysts 2017, 7, 328 19 of 23

InCatalysts an independent 2017, 7, 328 work, Cadierno, Gimeno and co-workers also explored the catalytic19 potentialof 23 of a series of arene-ruthenium(II) complexes containing different water-soluble phosphine ligands (42–45a–dInin an Figure independent7)[ 83]. work, All ofCadierno, them proved Gimeno to and the activeco-workers in the also addition explored of the benzoic catalytic acid to potential of a series of arene-ruthenium(II) complexes containing different water-soluble phosphine 1-phenyl-2-propyn-1-ol in pure water, leading to the desired β-oxo ester, i.e., 1-phenyl-2-oxopropyl ligands (42–45a–d in Figure 7) [83]. All of them proved to the active in the addition of benzoic acid to benzoate,1-phenyl-2-propyn-1-ol as the major reaction in pure water, product. leading Among to the desired them, β best-oxo ester, results i.e., in 1-phenyl-2-oxopropyl terms of activity and 6 selectivitybenzoate, were as the obtained major reac withtion the product. benzene Among derivative them, best [RuCl results2(η in-C terms6H6)(TPPMS)] of activity and (45a selectivity) (88% yield ◦ of 1-phenyl-2-oxopropylwere obtained with benzoatethe benzene after derivative 3 h of heating[RuCl2(η at6-C 1006H6)(TPPMS)]C using ( a45a ruthenium) (88% yield loading of of 2 mol1-phenyl-2-oxopropyl %). Concerning the benzoate scope of afte thisr complex,3 h of heating a variety at 100 of°C secondary using a ruthenium propargylic loading alcohols, of 2 mol as %). well as prop-2-yn-1-ol,Concerning couldthe scope be efﬁciently of this complex, transformed. a variety In contrast,of secondary tertiary propargylic propargylic alcohols, alcohols as well resulted as to be moreprop-2-yn-1-ol, challenging could substrates be efficiently and only transformed. those featuring In contrast, low tertiary sterically-demanding propargylic alcohols substituents resulted to led to highbe conversions. more challenging On the substrates other hand, and only45a wasthose operative featuring low with sterically-demanding a large variety of aromaticsubstituents carboxylic led acids,to bearing high conversions. different On functional the other hand, group 45a such was asoperative halide, with alkoxy, a large ketone variety or of sulfonamide.aromatic carboxylic The use acids, bearing different functional group such as halide, alkoxy, ketone or sulfonamide. The use of of heteroaromatic acids, with tetrahydrofuran, pyrrole, thiophene, indole or 2-oxo-2H-chromene heteroaromatic acids, with tetrahydrofuran, pyrrole, thiophene, indole or 2-oxo-2H-chromene fragments,fragments, as well as well as aliphatic as aliphatic acids acids was was also also tolerated. tolerated.

FigureFigure 7. Structure 7. Structure of of the the water-soluble water-soluble arene-ruthenium(II) complexes complexes 42–4245a––45ad. –d.

4. Conclusions4. Conclusions GreatGreat attention attention is currentlyis currently devoted devoted toto syntheticsynthetic organic organic chemistry chemistry in water in water and andresearch, research, particularlyparticularly in thein the field field of of aqueous aqueous catalysis, catalysis, isis increasingincreasing exponentially exponentially since since water water is the is most the most environmentally benign substitute for the volatile and toxic organic solvents commonly used in environmentally benign substitute for the volatile and toxic organic solvents commonly used in laboratories and industries. In this contribution, we have summarized the developments achieved in laboratoriesthe field and of industries.metal-catalyzed In this additions contribution, of carbox weylic have acids summarized to alkynes the in developmentsaqueous media. achieved Such in the fieldprocesses of metal-catalyzed now represent additions powerful oftools carboxylic for the cons acidstruction to alkynes of synthetically in aqueous useful media. lactones, Such processesenol nowesters represent and powerfulβ-oxo esters tools in an for atom-economical the construction manner. of synthetically Throughout useful this review lactones, article, enol we esters have and β-oxopresented esters in different an atom-economical catalytic systems manner. based on Throughout Pd, Pt, Au, this Cu reviewand Ru, article, capable we of havepromoting presented differentselectively catalytic these systems reactions based in aqueous on Pd, environmen Pt, Au, Cuts andwithout Ru, observing capableof the promoting competing selectivelyhydration of these reactionsthe alkyne in aqueous substrates. environments The vast majority without of observing the works the discussed competing herein hydration have been of published the alkyne during substrates. The vastthe last majority ten years, of demonstrating the works discussed clearly the herein current have interest been in this published research during field, which the lastobviously ten years, remains open, with many opportunities for new discoveries. demonstrating clearly the current interest in this research field, which obviously remains open, with manyAcknowledgments: opportunities for The new authors discoveries. acknowledge the Spanish MINECO (projects CTQ2013-40591-P and CTQ2016-75986-P) and the Gobierno del Principado de Asturias (project GRUPIN14-006) for financial support. Acknowledgments:Javier Francos thanksThe The authors Ministry acknowledge of Economy and the Competitiveness Spanish MINECO (MINECO) (projects and European CTQ2013-40591-P Social Fund and CTQ2016-75986-P)(ESF) for the award and of the a GobiernoJuan de la Cierva del Principado contract. de Asturias (project GRUPIN14-006) for financial support. Javier Francos thanks The Ministry of Economy and Competitiveness (MINECO) and European Social Fund (ESF) Author Contributions: Both authors analyzed the data and jointly wrote the paper. for the award of a Juan de la Cierva contract.

Author Contributions: Both authors analyzed the data and jointly wrote the paper. Catalysts 2017, 7, 328 20 of 23

Conﬂicts of Interest: The authors declare no conﬂict of interest.

References

1. Alonso, F.; Beletskaya, I.P.; Yus, M. Transition-metal-catalyzed addition of heteroatom-hydrogen bonds to alkynes. Chem. Rev. 2004, 104, 3079–3159. [CrossRef][PubMed] 2. Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Catalytic Markovnikov and anti-Markovnikov functionalization of alkenes and alkynes: Recent developments and trends. Angew. Chem. Int. Ed. 2004, 43, 3368–3398. [CrossRef] [PubMed] 3. Patil, N.T.; Kavthe, R.D.; Shinde, V.S. Transition metal-catalyzed addition of C-, N- and O-nucleophiles to unactivated C–C multiple bonds. Tetrahedron 2012, 68, 8079–8146. [CrossRef] 4. Hintermann, L. Recent developments in metal-catalyzed additions of oxygen nucleophiles to alkenes and alkynes. Top. Organomet. Chem. 2010, 31, 123–155. 5. Bruneau, C. Group 8 metals-catalyzed O–H bond addition to unsaturated molecules. Top. Organomet. Chem. 2013, 43, 203–230. 6. Abbiati, G.; Beccalli, E.M.; Rossi, E. Groups 9 and 10 metals-catalyzed O-H bond addition to unsaturated molecules. Top. Organomet. Chem. 2013, 43, 231–290. 7. Rao, Y.S. Recent advances in the chemistry of unsaturated lactones. Chem. Rev. 1976, 76, 625–694. [CrossRef] 8. Laduwahetty, T. Saturated and unsaturated lactones. Contemp. Org. Synth. 1995, 2, 133–149. [CrossRef] 9. Libiszewska, K. Lactones as biologically active compounds. Biotechnol. Food Sci. 2011, 75, 45–53. 10. Janecki, T. (Ed.) Natural Lactones and Lactams: Synthesis, Occurrence and Biological Activity; Wiley-VCH: Weinheim, Germany, 2013; ISBN 9783527334148. 11. Nea¸tu, F.; Toullec, P.Y.; Michelet, V.; Pârvulescu, V.I. Heterogeneous Au and Rh catalysts for the cycloisomerization reactions of γ-acetylenic carboxylic acids. Pure Appl. Chem. 2009, 81, 2387–2396. [CrossRef] 12. Bruneau, C.; Neveux, M.; Kabouche, Z.; Ruppin, C.; Dixneuf, P.H. Ruthenium-catalyzed additions to alkynes: Synthesis of activated esters and their use in acylation reactions. Synlett 1991, 11, 755–763. [CrossRef] 13. Kumar, M.; Bagchi, S.; Sharma, A. The ﬁrst vinyl acetate mediated organocatalytic transesteriﬁcation of phenols: A step towards sustainability. New J. Chem. 2015, 39, 8329–8336. [CrossRef] 14. Liu, X.; Coutelier, O.; Harrison, S.; Tassaing, T.; Marty, J.-D.; Destarac, M. Enhanced solubility of polyvinyl

esters in scCO2 by means of vinyl triﬂuorobutyrate monomer. ACS Macro Lett. 2015, 4, 89–93. [CrossRef] 15. Foarta, F.; Landis, C.R. Condensation oligomers with sequence control but without coupling reagents and protecting groups via asymmetric hydroformylation and hydroacyloxylation. J. Org. Chem. 2016, 81, 11250–11255. [CrossRef][PubMed] 16. Jena, R.K.; Das, U.K.; Ghorai, A.; Bhattacharjee, M. Ruthenium-catalyzed addition of carboxylic acids to progargylic alcohols: An easy route to O-dienyl esters and their tandem atom-transfer radical polymerization. Eur. J. Org. Chem. 2016, 6015–6021. [CrossRef] 17. Konrad, T.M.; Schmitz, P.; Leitner, W.; Franciò, G. Highly enantioselective Rh-catalysed hydrogenation of 1-alkyl vinyl esters using phosphine-phosphoramidite ligands. Chem. Eur. J. 2013, 19, 13299–13303. [CrossRef][PubMed] 18. González-Liste, P.J.; León, F.; Arribas, I.; Rubio, M.; García-Garrido, S.E.; Cadierno, V.; Pizzano, A. Highly stereoselective synthesis and hydrogenation of (Z)-1-alkyl-2-arylvinyl acetates: A wide scope procedure for the preparation of chiral homobenzylic esters. ACS Catal. 2016, 6, 3056–3060. [CrossRef] 19. León, F.; González-Liste, P.J.; García-Garrido, S.E.; Arribas, I.; Rubio, M.; Cadierno, V.; Pizzano, A. Broad scope synthesis of ester precursors of nonfunctionalized chiral alcohols based on the asymmetric hydrogenation of α,β-dialkyl-, α,β-diaryl-, and α-alkyl-β-aryl-vinyl esters. J. Org. Chem. 2017, 82, 5852–5867. [CrossRef][PubMed] 20. Takeno, M.; Kikuchi, S.; Morita, S.-I.; Nishiyama, Y.; Ishii, Y. A new coupling reaction of vinyl esters with aldehydes catalyzed by organosamarium compounds. J. Org. Chem. 1995, 60, 4974–4975. [CrossRef] 21. Goossen, L.J.; Paetzold, J. Decarbonylative Heck oleﬁnation of enol esters: Salt-free and environmentally friendly access to vinyl arenes. Angew. Chem. Int. Ed. 2004, 43, 1095–1098. [CrossRef][PubMed] 22. Geibel, I.; Dierks, A.; Schmidtmann, M.; Christoffers, J. Formation of δ-lactones by cerium-catalyzed, Baeyer-Villiger-type coupling of β-oxoesters, enol acetates, and dioxygen. J. Org. Chem. 2016, 81, 7790–7798. [CrossRef][PubMed] Catalysts 2017, 7, 328 21 of 23

23. González-Liste, P.J.; Francos, J.; García-Garrido, S.E.; Cadierno, V. The intermolecular hydro-oxycarbonylation of internal alkynes: Current state of the art. Arkivoc 2018, Part II, 17–39. 24. Cornils, B.; Herrmann, W.A. (Eds.) Aqueous-Phase Organometallic Catalysis, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2004; ISBN 3527307125. 25. Li, C.-J.; Chan, T.-H. Comprehensive Organic Reactions in Aqueous Media, 2nd ed.; John Wiley & Sons: Hoboken, NJ, USA, 2007; ISBN 9780471761297. 26. Dixneuf, P.H.; Cadierno, V. (Eds.) Metal-Catalyzed Organic Reactions in Water; Wiley-VCH: Weinheim, Germany, 2013; ISBN 9783527331888. 27. Benaglia, M. (Ed.) Recoverable and Recyclable Catalysts; John Wiley & Sons: Chichester, UK, 2009; ISBN 9780470681954. 28. Chen, L.; Li, C.-J. Catalytic reactions of alkynes in water. Adv. Synth. Catal. 2006, 348, 1459–1484. [CrossRef]

29. Wakabayashi, T.; Ishii, Y.; Ishikawa, K.; Hidai, M. A novel catalyst with a cuboidal PdMo3S4 core for the cyclization of alkynoic acids to enol lactones. Angew. Chem. Int. Ed. 1996, 35, 2123–2124. [CrossRef] 30. García-Álvarez, J.; Díez, J.; Vidal, C. Pd(II)-catalyzed cycloisomerisation of γ-alkynoic acids and one-pot tandem cycloisomerisation/CuAAC reactions in water. Green Chem. 2012, 14, 3190–3196. [CrossRef] 31. Phillips, A.D.; Gonsalvi, L.; Romerosa, A.; Vizza, F.; Peruzzini, M. Coordination chemistry of 1,3,5-triaza-7-phosphaadamantane (PTA): Transition metal complexes and related catalytic, medicinal and photoluminescent applications. Coord. Chem. Rev. 2004, 248, 955–993. [CrossRef] 32. Bravo, J.; Bolaño, S.; Gonsalvi, L.; Peruzzini, M. Coordination chemistry of 1,3,5-triaza-7-phosphaadamantane (PTA) and derivatives. Part II. The quest for tailored ligands, complexes and related applications. Coord. Chem. Rev. 2010, 254, 555–607. [CrossRef] 33. Ogata, K.; Sasano, D.; Yokoi, T.; Isozaki, K.; Seike, H.; Takaya, H.; Nakamura, M. Pd-complex bound amino acid-based supramolecular gel catalyst for intramolecuar addition-cyclization of alkynoic acids in water. Chem. Lett. 2012, 41, 498–500. [CrossRef] 34. Hamasaka, G.; Uozumi, Y. Cyclization of alkynoic acids in water in the presence of a vesicular self-assembled amphiphilic pincer palladium complex catalyst. Green Chem. 2014, 50, 14516–14518. [CrossRef][PubMed] 35. Michelet, V.; Toullec, P.Y.; Genêt, J.-P. Cycloisomerization of 1,n-enynes: Challenging metal-catalyzed rearrangements and mechanistic insights. Angew. Chem. Int. Ed. 2008, 47, 4268–4315. [CrossRef][PubMed] 36. Soriano, E.; Marco-Contelles, J. Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes. Acc. Chem. Res. 2009, 42, 1026–1036. [CrossRef][PubMed] 37. Ke, D.; Espinosa, N.A.; Mallet-Ladeira, S.; Monot, J.; Martin-Vaca, B.; Bourissou, D. Efﬁcient synthesis of unsaturated δ- and ε-lactones/lactams by catalytic cycloisomerization: When Pt outperforms Pd. Adv. Synth. Catal. 2016, 358, 2324–2331, and references therein. [CrossRef] 38. Alemán, J.; del Solar, V.; Navarro-Ranninger, C. Anticancer platinum complexes as non-innocent compounds for catalysis in aqueous media. Chem. Commun. 2010, 46, 454–456. [CrossRef][PubMed] 39. Alemán, J.; del Solar, V.; Cubo, L.; Quiroga, A.G.; Navarro-Ranninger, C. New reactions of anticancer-platinum complexes and their intriguing behavior under various experimental conditions. Dalton Trans. 2010, 39, 10601–10607. [CrossRef][PubMed] 40. Hashmi, A.S.K.; Toste, F.D. (Eds.) Modern Gold Catalyzed Synthesis; Wiley-VCH: Weinheim, Germany, 2012; ISBN 9783527319527. 41. Toste, F.D.; Michelet, V. (Eds.) Gold Catalysis: An Homogeneous Approach; Imperial College Press: London, UK, 2014; ISBN 9781848168527. 42. Genin, E.; Toullec, P.Y.; Antoniotti, S.; Brancour, C.; Genêt, J.-P.; Michelet, V. Room temperature Au(I)-catalyzed exo-selective cycloisomerization of acetylenic acids: An entry to functionalized γ-lactones. J. Am. Chem. Soc. 2006, 128, 3112–3113. [CrossRef][PubMed]

43. Toullec, P.Y.; Genin, E.; Antoniotti, S.; Genêt, J.-P.; Michelet, V. Au2O3 as a stable and efﬁcient catalyst for the selective cycloisomerization of γ-acetylenic carboxylic acids to γ-alkylidene-γ-butyrolactones. Synlett 2008, 707–711. 44. Tomás-Mendivil, E.; Toullec, P.Y.; Díez, J.; Conejero, S.; Michelet, V.; Cadierno, V. Cycloisomerization versus hydration reactions in aqueous media: A Au(III)-NHC catalyst that makes the difference. Org. Lett. 2012, 14, 2520–2523. [CrossRef][PubMed] Catalysts 2017, 7, 328 22 of 23

45. Tomás-Mendivil, E.; Toullec, P.Y.; Borge, J.; Conejero, S.; Michelet, V.; Cadierno, V. Water-soluble gold(I) and gold(III) complexes with sulfonated N-heterocyclic carbene ligands: Synthesis, characterization, and application in the catalytic cycloisomerization of γ-alkynoic acids into enol-lactones. ACS Catal. 2013, 3, 3086–3098. [CrossRef] 46. Ferré, M.; Cattoën, X.; Wong Chi Man, M.; Pleixats, R. Sol-gel immobilized N-heterocyclic carbene gold complex as a recyclable catalyst for the rearrangement of allylic esters and the cycloisomerization of γ-alkynoic acids. ChemCatChem 2016, 8, 2824–2831. [CrossRef] 47. Belger, K.; Krause, N. Smaller, faster, better: Modular synthesis of unsymmetrical ammonium salt-tagged NHC-gold(I) complexes and their application as recyclable catalysts in water. Org. Biomol. Chem. 2015, 13, 8556–8560. [CrossRef][PubMed] 48. Rodríguez-Álvarez, M.J.; Vidal, C.; Díez, J.; García-Álvarez, J. Introducing deep eutectic solvents as biorenewable media for Au(I)-catalysed cycloisomerisation of γ-alkynoic acids: An unprecedented catalytic system. Chem. Commun. 2014, 50, 12927–12929. [CrossRef][PubMed] 49. Mindt, T.L.; Schibli, R. Cu(I)-catalyzed intramolecular cyclization of alkynoic acids in aqueous media: A “click side reaction”. J. Org. Chem. 2007, 72, 10247–10250. [CrossRef][PubMed] 50. López-Reyes, M.E.; Toscano, R.A.; López-Cortés, J.G.; Alvarez-Toledano, C. Fast and efﬁcient synthesis of Z-enol-γ-lactones through a cycloisomerization reaction of β-hydroxy-γ-alkynoic acids catalyzed by copper(I) under microwave heating in water. Asian J. Org. Chem. 2015, 4, 545–551. [CrossRef] 51. Li, S.; Jia, W.; Jiao, N. Copper/iron-cocatalyzed highly selective tandem reactions: Efﬁcient approaches to Z-γ-alkylidene lactones. Adv. Synth. Catal. 2009, 351, 569–575. [CrossRef]

52. Jia, W.; Li, S.; Yu, M.; Chen, W.; Jiao, N. AgNO3 catalyzed cyclization of propargyl-Meldrum´s acids in aqueous solvent: Highly selective synthesis of Z-γ-alkylidene lactones. Tetrahedron Lett. 2009, 50, 5406–5408. [CrossRef] 53. Ahmar, S.; Fillion, E. Expedient synthesis of complex γ-butyrolactones from 5-(1-arylalkylidene) Meldrum´s acids via sequential conjugate alkynylation/Ag(I)-catalyzed lactonization. Org. Lett. 2014, 16, 5748–5751. [CrossRef][PubMed] 54. Liu, W.; Xu, D.D.; Repiˇc,O.; Blacklock, T.J. A mild method for ring-opening aminolysis of lactones. Tetrahedron Lett. 2001, 42, 2439–2441. [CrossRef] 55. Guo, W.; Gómez, J.E.; Martínez-Rodríguez, L.; Bandeira, N.A.G.; Bo, C.; Kleij, A.W. Metal-free synthesis of N-aryl amides using organocatalytic ring-opening aminolysis of lactones. ChemSusChem 2017, 10, 1969–1975. [CrossRef][PubMed] 56. Yang, T.; Campbell, L.; Dixon, D.J. A Au(I)-catalyzed N-acyl iminium ion cyclization cascade. J. Am. Chem. Soc. 2007, 129, 12070–12071. [CrossRef][PubMed] 57. Feng, E.; Zhuo, Y.; Zhang, D.; Zhang, L.; Sun, H.; Jiang, H.; Liu, H. Gold(I)-catalyzed tandem transformation: A simple approach for the synthesis of pyrrolo/pyrido[2,1-a][1,3]benzoxazinones and pyrrolo/pyrido[2,1-a]quinazolinones. J. Org. Chem. 2010, 75, 3274–3282. [CrossRef][PubMed] 58. Patil, N.T.; Lakshmi, P.G.V.V.; Sridhar, B.; Patra, S.; Bhadra, M.P.; Patra, C.R. New linearly and angularly fused quinazolinones: Synthesis through gold(I)-catalyzed cascade reactions and anticancer activities. Eur. J. Org. Chem. 2012, 1790–1799. [CrossRef] 59. Li, Z.; Li, J.; Yang, N.; Chen, Y.; Zhou, Y.; Ji, X.; Zhang, L.; Wang, J.; Xie, X.; Liu, H. Gold(I)-catalyzed cascade

approach for the synthesis of tryptamine-based polycyclic privileged scaffolds as α1-adrenergenic receptor antagonists. J. Org. Chem. 2013, 76, 10802–10811. [CrossRef][PubMed] 60. Feng, E.; Zhou, Y.; Zhao, F.; Chen, X.; Zheng, L.; Jiang, H.; Liu, H. Gold-catalyzed tandem reaction in water: An efficient and convenient synthesis of fused polycyclic indoles. Green Chem. 2012, 14, 1888–1895. [CrossRef] 61. Zhuo, Y.; Zhai, Y.; Ji, X.; Liu, G.; Feng, E.; Ye, D.; Zhao, L.; Jiang, H.; Liu, H. Gold(I)-catalyzed one-pot tandem coupling/cyclization: An efficient synthesis of pyrrolo-/pyrido[2,1-b]benzo[d][1,3]oxazin-1-ones. Adv. Synth. Catal. 2010, 352, 373–378. [CrossRef] 62. Zhou, L.; Jiang, H.-F. Synthesis of phthalides via Pd/CNTs-catalyzed reaction of terminal alkynes and o-iodobenzoic acid under copper- and ligand-free conditions. Tetrahedron Lett. 2007, 48, 8449–8452. [CrossRef] 63. García-Álvarez, J.; Díez, J.; Gimeno, J. A highly efficient copper(I) catalyst for the 1,3-dipolar addition of azides with terminal and 1-iodoalkynes in water: Regioselective synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles. Green Chem. 2010, 12, 2127–2130. [CrossRef] Catalysts 2017, 7, 328 23 of 23

64. Denard, C.A.; Hartwig, J.F.; Zhao, H. Multistep one-pot reactions combining biocatalysts and chemical catalysts for asymmetric synthesis. ACS Catal. 2013, 3, 2856–2864. [CrossRef] 65. Gröger, H.; Hummel, W. Combining the ‘two worlds’ of chemocatalysis and biocatalysis towards multi-step one-pot processes in aqueous media. Curr. Opin. Chem. Biol. 2014, 19, 171–179. [CrossRef][PubMed] 66. Wallace, S.; Balskus, E.P. Opportunities for merging chemical and biological synthesis. Curr. Opin. Biotechnol. 2014, 30, 1–8. [CrossRef][PubMed] 67. Rodríguez-Álvarez, M.J.; Ríos-Lombardía, N.; Schumacher, S.; Pérez-Iglesias, D.; Morís, F.; Cadierno, V.; García-Álvarez, J.; González-Sabín, J. Combination of metal-catalyzed cycloisomerizations and biocatalysis in aqueous media: Asymmetric construction of chiral alcohols, lactones and γ-hydroxy-carbonyl compounds. ACS Catal. 2017, 7, 7753–7759. [CrossRef] 68. Cadierno, V.; Francos, J.; Gimeno, J. Ruthenium(IV)-catalyzed Markovnikov addition of carboxylic acids to terminal alkynes in aqueous medium. Organometallics 2011, 30, 852–862. [CrossRef] 69. Chanda, A.; Fokin, V.V. Organic synthesis ”on water”. Chem. Rev. 2009, 109, 725–748. [CrossRef][PubMed] 70. Butler, R.N.; Coyne, A.G. Water: Nature’s reaction enforcer—Comparative effects for organic synthesis “in-water” and “on-water”. Chem. Rev. 2010, 110, 6302–6337. [CrossRef][PubMed] 71. Nicks, F.; Aznar, R.; Sainz, D.; Muller, G.; Demonceau, A. Novel, highly efﬁcient and selective ruthenium catalysts for the synthesis of vinyl esters from carboxylic acids and alkynes. Eur. J. Org. Chem. 2009, 5020–5027. [CrossRef] 72. Kleman, P.; González-Liste, P.J.; García-Garrido, S.E.; Cadierno, V.; Pizzano, A. Highly enantioselective hydrogenation of 1-alkylvinyl benzoates: A simple, nonenzymatic access to chiral 2-alkanols. Chem. Eur. J. 2013, 19, 16209–16212. [CrossRef][PubMed] 73. Kleman, P.; González-Liste, P.J.; García-Garrido, S.E.; Cadierno, V.; Pizzano, A. Asymmetric hydrogenation of 1-alkyl and 1-aryl vinyl benzoates: A broad scope procedure for the highly enantioselective synthesis of 1-substituted ethyl benzoates. ACS Catal. 2014, 4, 4398–4408. [CrossRef] 74. González-Liste, P.J.; García-Garrido, S.E.; Cadierno, V. Gold(I)-catalyzed addition of carboxylic acids to internal alkynes in aqueous medium. Org. Biomol. Chem. 2017, 15, 1670–1679. [CrossRef][PubMed] 75. Scheid, G.; Kuit, W.; Ruijter, E.; Orru, R.V.A.; Henke, E.; Bornscheuer, U.; Wessjohann, L.A. A new route to protected acyloins and their enzymatic resolution with lipases. Eur. J. Org. Chem. 2004, 1063–1074. [CrossRef] 76. Carpino, P.A.; Grifﬁth, D.A.; Sakya, S.; Dow, R.L.; Black, S.C.; Hadcock, J.R.; Iredale, P.A.; Scott, D.O.;

Fichtner, M.W.; Rose, C.R.; et al. New bicyclic cannabinoid receptor-1 (CB1-R) antagonists. Bioorg. Med. Chem. Lett. 2006, 16, 731–736. [CrossRef][PubMed] 77. Lu, H.-L.; Wu, Z.-W.; Song, S.-Y.; Liao, X.-D.; Zhu, Y.; Huang, Y.-S. An improved synthesis of nomegestrol acetate. Org. Process Res. Dev. 2014, 18, 431–436. [CrossRef] 78. Kaila, N.; Janz, K.; DeBernardo, S.; Bedard, P.W.; Camphausen, R.T.; Tam, S.; Tsao, D.H.H.; Keith, J.C.; Nickerson-Nutter, C.; Shilling, A.; Young-Sciame, R.; Wang, Q. Synthesis and biological evaluation of quinoline salicylic acids as P-Selectin antagonists. J. Med. Chem. 2007, 50, 21–39. [CrossRef][PubMed] 79. Ruiz, J.F.M.; Radics, G.; Windle, H.; Serra, H.O.; Simplício, A.L.; Kedziora, K.; Fallon, P.G.; Kelleher, D.P.; Gilmer, J.F. Design, synthesis, and pharmacological effects of a cyclization-activated steroid prodrug for colon targeting in inﬂammatory bowel disease. J. Med. Chem. 2009, 52, 3205–3211. [CrossRef][PubMed] 80. Jeschke, J.; Korb, M.; Rüffer, T.; Gäbler, C.; Lang, H. Atom economic ruthenium-catalyzed synthesis of bulky β-oxo esters. Adv. Synth. Catal. 2015, 357, 4069–4081, and references therein. [CrossRef] 81. Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. Ruthenium-catalyzed selective addition of carboxylic acids to alkynes. A new synthesis of enol esters. J. Org. Chem. 1987, 52, 2230–2239. [CrossRef] 82. Bauer, E. Transition-metal-catalyzed functionalization of propargylic alcohols and their derivatives. Synthesis 2012, 44, 1131–1151. [CrossRef] 83. Cadierno, V.; Francos, J.; Gimeno, J. Ruthenium-catalyzed synthesis of β-oxo esters in aqueous medium: Scope and limitations. Green Chem. 2010, 12, 135–143. [CrossRef]

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