Transition metal-catalyzed addition of C-, N- and O-nucleophiles to unactivated C–C multiple bonds

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

“…The first example of such reactions in an aqueous environment was described by Hidai and co-workers in 1996 employing the mixed-metal cubane-type cluster complex [PdMo 3 S 4 (tacn) 3 Cl][PF 6 ] 3 (1; tacn = 1,4,7-triazacyclononane) as catalyst [29]. Thus, they found that, in combination with NEt 3 , 1 was able to transform dipropargylmalonic acid 2 into the enol lactone 3 in water at room temperature (Scheme 3).…”

“…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][2][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][5][6].…”

“…Thus, the intramolecular version of the process, i.e., the cycloisomerization of alkynoic acids, produces unsaturated lactones (Scheme 1) which are common structural motifs found in natural products and biologically active molecules, as well as valuable synthetic intermediates [7][8][9][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][2][3][4][5][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][2][3][4][5][6].…”

“…In addition, the use of water (or aqueous biphasic mixtures) allows in many cases an easy catalyst/product separation, thus allowing the effective recycling of the catalytically active species, which is another key aspect in the Green Chemistry context [27]. However, despite the growing interest in aqueous catalysis, the use of this environmentally benign solvent in the hydrocarboxylation of alkynes been for long time neglected, probably due to the concerns of a competing hydration of the alkyne substrates to form carbonyl compounds, a process that is also catalyzed by transition metals [1][2][3][4][5][6]28]. In fact, in a general review on the "catalytic reactions of alkynes in water", published by Chen and Li in 2006, no examples of hydrocarboxylation reactions were collected [28].…”

“…For example, to name just a few of their myriad applications, they are widely employed as mild acylating reagents [12,13], as monomers in diverse polymerization reactions [14][15][16], as substrates in asymmetric hydrogenation for the generation of enantioenriched alcohols [17][18][19], or as starting materials for different cross-coupling processes [20][21][22]. As for the cycloisomerization of alkynoic acids, a huge number of catalytic systems involving late transition metals have been described, with those based on ruthenium playing a prominent role [1][2][3][4][5]. However, for a long time, this reaction was limited to terminal alkynes, since most catalysts failed to enable the hydrocarboxylation of internal alkynes as a consequence of their greater steric hindrance, which disfavours their coordination to the metal catalyst.…”