Alkynes activated, oxidative coupling

Coupling of Arylboronic Acids with Alkynes. The oxidative coupling of arylboronic acids with internal alkynes effectively proceeded under [Cp RhCl2]2-Cu(OAc)2 catalytic system in a 1 2 manner via C-H bond activation to produce the corresponding product (eq 24) It is noted that the electron-deficient phenyl-boronic acids were less reactive in the present reaction. 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

Cyclometallation (also called oxidative coupling) is a rather special case of oxidative addition. In this reaction, two unsaturated molecules, X=Y and X =Y, add to the same metal atom M. One of the X—Y bonds and one of the X —Y bonds are broken, and new M X and M -Y bonds form. However, a new Y—Y bond also forms, and the overall result is a cyclometaUated compound (Figure 3.7a). As in oxidative addition, the oxidation state of the metal center increases by 2. Cyclometallation is common with alkynes (Figure 3.7b), as well as with alkenes activated by electron-withdrawing groups [21]. 

Nickel-catalyzed cyclizations, couplings, and cycloadditions involving three reactive components have been an active area of research for the past decade [39,40]. Central to these reactions is the involvement of a low-valent nickel capable of facilitating oxidative coupling of an unsaturated hydrocarbon (such as an alkyne, allene, or alkene) and a carbonyl substrate (such as an aldehyde or ketone). The use of NHCs as ligands has been evaluated for couplings of aldehydes. Such reactions typically afford O-protected allylic alcohols in good yields. 

The Sonogashira coupling can be considered a special case of catalytic alkyne activation. Interestingly, it is also possible to conduct alkyne activation under oxidative conditions in the presence of Pd catalysts without oxidative dimerization. Here, Costa and coworkers [139] have developed a Pd-catalyzed sequential carboxylation-alkoxycarbonylation of acetylenic amines in the presence of oxygen to give mixtures of Z- and -configurcd 2-oxo-oxazolidin-5-ylidene]-acetic acid methyl ester 193 and 194 in good to excellent yields (Scheme 75). 

Many methods of ruthenium-promoted C-C bond formation implicating alkynes have been discovered. Most of these have involved oxidative coupling at a ruthe-nium(O) or (II) site, rather than addition of carbonucleophiles to electrophilically activated alkynes. These methods have been reported in several reviews [3,122]. 

The sp C-H bonds of terminal alkynes are well known to become activated by metal salts in the presence of bases. A variety of research groups have examined the use of terminal alkynes as nucleophiles for the oxidative addition to the C-H bond adjacent to the nitrogen atom of amines. Li and co-workers examined the oxidative coupling of /V,/V-dimethylaniline 26 with 1-alkynes 27 (Scheme 15) [31, 32]. 

Another Pd-catalyzed synthesis of pyrroles 14 was reported whereby enamides 12 were coupled to alkynes 13 via a C—H activation oxidative... 

Recently, Fagnou reported a very interesting, atom-economical route to the 1,2,3-trisubstituted indole derivatives 273 via the Rh(II)-catalyzed oxidative coupling-indolization reaction (Scheme 9.95) [251]. Accordingly, simple acetanilides 271, upon a directed C-H activation with the Rh(II)-catalyst [252] followed by a subsequent carborhodation-indolization sequence of alkyne 272, gave N-acylated indoles 273. Both electron-rich and electron-deficient acetanilides 271, possessing different functionalities were perfectly tolerated under these reaction conditions. In the case of unsymmetrical alkyl-alkyl-substituted acetylenes, a mixture of indole products... 

The formation of 2-alkenyl-substituted furans was observed in the palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones. This reaction involved oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, P-hydride elimination, and catalyst regeneration (13JA13502). 

Disubstituted isocoumarins arise from the copper(II)-catalyzed addition of o-halobenzoic acids to active internal alkynes (13JOC1660), rhodium(III)-mediated oxidative coupling ofbenzoic acids with disubsti-tuted alkynes (13T4454), palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone (13T8626), and nickel(II)-promoted t-butyl isocyanide insertion in 2-(o-bromophenyl)-1-ethanones followed by hydrolysis (Scheme 69) (13SC3262). 

Xie and Qiu have reported the first example of the [2+2+2] carboannulation of arynes, activated alkenes, and arynes. Whereas Pd catalysts promote the two-component benzyne-alkene-benzyne cyclization, under Ni catalysis the three-component reaction is favored leading to 1,2-dihydronaphthalenes 108 from readily available materials. In this case, the catalytic cycle is likely initiated by oxidative coupling of aryne and alkene on Ni to form a nickelacycle that undergoes subsequent insertion of the alkyne into the Ni-C(aryl) bond to give a seven-membered intermediate (Scheme 12.54) [95]. 

The preparation of isocoumarins from the oxidative coupling of benzoic acids with alkynes in MeOH with oxidant AgOAc is catalysed by [Cp lrCl2]2 complex. Alkyl alkynes are more reactive than aryl alkynes. The DFT calculations of intermediates and transition states reveal that C-H activation occurs via an acetate-assisted meehanism, the C-H activation is not turnover limiting and the AgOAc oxidizes the reduced form of the catalyst via an Ir(I)-lr(ll)-Ir(IIl) sequence. ... 

The mechanism of the RuAAC reaction has been investigated by several groups and is summarized in Scheme 9.6. The proposed catalytic cycle includes the formation of the catalytically active species [Cp RuCl] and the formal substitution of the spectator ligands by the alkyne 40 and the azide 41 to give complex 42. After oxidative coupling of the alkyne and the azide, the intermediate species 43 undergoes reductive elimination and releases the aromatic triazole product 45. 

The title compound is a highly effective catalyst for the oxidative cycloaddition of benzamides and alkynes via C-H activation (eq 4) The reaction proceeded via an initial N-H metalation of the amide followed by ortho C-H activation. The oxidative couplings of benzophenone imines (eq 5) and benzamidines with... 

The catalytic activation of alkynes and alkenes by (CsR5)Ru complexes has been extensively explored during the past decade and can lead to the creation of carbon-carbon bonds, often via the formation of a ruthenacycle intermediate after an oxidative coupling process. [2+2+2] Cycloadditions, cycloisomerizations, or dienes formation are examples of the versatility of theses complexes. The diversity and the selectivity (regio- and often stereoselectivity) of these reactions, which can proceed under mild conditions [134—136], show the interest of (CsR5)Ru catalysts for new synthetic methodologies and the future potential in organic synthesis. 

In 2007, the Mlura group reported a Rh(III)-catalyzed oxidative coupling of benzoic acids with internal alkynes to the synthesis of isocoumarins via aromatic C-H activation (Scheme 6.24a) [38]. Importantly, the reaction of benzoic acids with alkynes takes place efficiently even with a reduced amount (5mol%) of Cu(0Ac)2-H20 under air (Scheme 6.24b) [5b]. The same group also developed the rhodium-catalyzed coupling of acrylic acids with alkynes to provide corresponding a-pyrone via vinylic C-H bond cleavage (Scheme 6.24c) [5c]. In 2015, Wen and coworkers described a Rh(III)-catalyzed synthesis of... 

Recently, it has been demonstrated that coordination vacancies on the surface metal cations are relevant to the unique redox reactivity of oxide surfaces]2]. Oxidation of fonnaldehyde and methyl formate to adsorbed formate intermediates on ZnO(OOOl) and reductive C-C coupling of aliphatic and aromatic aldehydes and cyclic ketones on 1102(001) surfaces reduced by Ar bombardment are observed in temperature-prognunmed desorption(TPD). The thermally reduced 1102(110) surface which is a less heavily damaged surface than that obtained by bombardment and contains Ti cations in the -t-3 and +4 states, still shows activity for the reductive coupling of formaldehyde to form ethene]13]. Interestingly, the catalytic cyclotrimerization of alkynes on TiO2(100) is also traced in UHV conditions, where cation coordination and oxidation states appear to be closely linked to activity and selectivity. The nonpolar Cu20( 111) surface shows a... 

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