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 b-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; b-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 p-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]. Catalysts 2017, 7, 328; doi:10.3390/catal7110328 www.mdpi.com/journal/catalysts Catalysts 2017, 7, 328 2 of 23 Catalysts 2017, 7, 328 2 of 23 Catalysts 2017, 7, 328 2 of 23 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