Hydroarylation, alkynes

An excellent recent review covers metal-catalyzed alkyne hydroarylations in detail.145... 

Thanks to a recent renaissance in gold catalysis, new gold-mediated transformations are being discovered with ever-increasing frequency. Some of these discoveries have been attributed to the action of gold vinylidenes. Fiirstner and coworkers uncovered one such example while screening catalysts for intramolecular alkyne hydroarylation (Scheme 9.23) [46]. 

Scheme 9.23 Metal-dependent cyclization modes in intramolecular alkyne hydroarylation.

Rhodium migration has also been observed in the rhodium-catalyzed reaction of aryl boronic acids (or equivalents) with alkynes or enynes. Three reports have been disclosed in the literature [79-81], The first is an alkyne hydroarylation method reported by Hayashi and coworkers (Scheme 20) [79], It was observed that under the standard rhodium-catalyzed hydroarylation conditions, protonolysis does not occur on the rhodium-bearing vinylic site, but rather on the aromatic ring after an apparent rhodium migration. 

Reactions of alkynes. Hydroarylation, " carbonylation, and the formation of a-substituted acrylamides-- are some of the reactions mediated by PdfOAc),. While an intramolecular version of the former completes a synthesis of coumarins and quin-olinones, the latter two incorporate CO group(s) from carbon monoxide. 

Very recently, the enantio- and diastereoselective synthesis of an S-shaped double azahelicene has been achieved via the gold-catalyzed sequential intramolecular alkyne hydroarylation (Scheme 21.51) [57]. 

Hydroarylation of Alkynes. Hydroarylation of propynoic acid derivatives with indoles was achieved via an intermolecu-lar Fe-catalyzed, Ag-mediated process, providing access to 3,3 -bis(indolyl)propanoic acid derivatives. A catalytic system of 5 mol % FeCls and 15 mol% AgOTf in AcOH at 40 °C for 36 h regioselectively produced ethyl 3,3-bis( l//-indol-3-yl)propanoate in 86% yield (eq 71). 

Keywords Alkene hydroarylation Alkenylation Alkylation Alkyne hydroarylation Annulations Arylation C-C bond cross-couplings Heteroaiylation Ruthenmm(ll) catalysis sp C-H bond activation... 

Biffis A, Tubaro C, Buscemi G, Basato M. Highly efficient alkyne hydroarylation with chelating dicarbene paUadium(II) and platinum(II) complexes. Adv Synth Catal. 2008 350 189-196. 

Biffis A, GazzolaL, Gobbo P, Buscemi G, Tubaro C, Basato M. Alkyne hydroarylations with chelating dicarbene paUadium(n) complex catalysts improved and imexpected reactivity patterns disclosed upon additive screening. Eur J Org Chem. 2009 2009 3189-3198. 

Biffis A, Gazzola L, Tubaro C, Basato M. Alkyne hydroarylation in ionic liquids catalyzed by paUadium(II) complexes. ChemSusChem. 2010 3 834-839. 

Although less studied than O- and N-nueleophiles, other nueleophilic partners possessing H-X bonds can participate in gold-eatalyzed hydrofunctionalization reactions. Hence, the intermoleeular hydroarylation ie. C(sp2)-H bond addition] of allenes with indoles was reported in the presence of [(IPr) AuCl]. Using the same catalyst, Che and co-workers investigated an interesting cascade terminated by an alkyne hydroarylation step. The intramolecular allene hydroarylation with indoles was also described by Alcaide and Almendros. ... 

Scheme 20 Mechanism for iron-catalyzed tandem coupling/hydroarylation of aldehyde, aromatic alkyne, and anilines...

Hydroarylation, (addition of H-Ar, Ar = aryl), of alkynes, catalysed by Pd(OOCCH3)2 or Pd(OOCCFj)j in acetic acid, is an atom-economic reaction, giving rise to substituted c/i-stilbenes (Fujiwara reaction). Catalytic conversions and improved chemoselectivity to the mono-coupled product under mild conditions can be achieved by modification of the metal coordination sphere with NHC ligands. Hydroarylation of mesitylene by ethylpropiolate (Scheme 2.19) catalysed by complex 107 (Fig. 2.18) proceeds in good conversions (80-99%, 1 mol%) under mild conditions at room temperature. 

COOEt COOEt Scheme 2.19 Products from the hydroarylation reactions of activated alkynes... 

Fig. 2.18 PaUadium and platinum NHC complexes as catalysts in hydroarylations of alkynes...

Gold as an efficient catalyst has widely been used in furan synthesis. One example is shown below, in which the double hydroarylation of unactivated alkyne using 2-methylfuran afforded a difuranylmethane derivative in a moderate yield <06EJOC4340>. 

Coumarins are formed by the intramolecular hydroarylation of an activated alkyne. The basic starting materials for this fast, efficient and general Pd-catalysed reaction are phenols and alkynoic acids (Scheme 42), An intermolecular version in which electron-rich phenols react with 4-methoxycinnamic acid leads to high yields of 3,4-dihydrocoumarins... 

Hydroarylations of alkynes are catalyzed by gold complexes and these bear some resemblance to the Fujiwara Pd-catalyzed reaction. In general, when using gold chemistry, better Z/E selectivities are observed compared with palladium, lower catalyst loadings and milder conditions (neutral not TFA) are used. The mechanism involves the attack of ArH on the Au-coordinated alkyne. Flowever, electron-poor acetylenes only appear to work with palladium chemistry (Equations (75) and (76)).72... 

Coumarins and quinolinones can be formed by hydroarylation reactions of alkynes (Equations (172)-(174)).7U42 142a... 

Similar intramolecular hydroarylations of alkynes and alkenes, which obviate the need for a halide or triflate group on the aryl ring, are now well established. Sames group screened over 60 potential catalysts and over 200 reaction conditions, and found that Ru(m) complexes and a silver salt were optimal. This process appears to tolerate steric hindrance and halogen substrates on the arene (Equations (175)—(177)). The reaction is thought to involve alkene-Ru coordination and an electrophilic pathway rather than a formal C-H activation of the arene followed by alkene hydrometallation, and advocates the necessary cautious approach to labeling this reaction as a C-H functionalization... 

Dinuclear palladium complexes catalyze m-hydroarylation of alkynes with arenes.56 The reaction of 3-hexyne with benzene in the presence of a dinulear palladium complex Pd2R2(M-OH)(//-dpfam) [dpfam = j/V,Ar -bis[2-(diphenyl-phosphino)phenyl]formamidinate, R=/>-Tol] and tri(/z-butyl)borane at 100 °C for 4h affords ( )-3-phenyl-3-hexene quantitatively (Equation (53)). The hydroarylation of 3-hexyne with monosubstituted benzenes ( )-3-aryl-3-hexenes with a 2 1 ratio of the meta- and ra -isomers. This regioselectivity is different from that of the hydroarylation of diphenylacetylene catalyzed by Rh4(GO)12.57... 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

Insertion of aUcynes into aromatic C-H bonds has been achieved by iridium complexes. Shibata and coworkers found that the cationic complex [Ir(COD)2]BF4 catalyzes the hydroarylation of internal alkynes with aryl ketones in the presence of BINAP (24) [111]. The reaction selectively produces ort/to-substituted alkenated-aryl products. Styrene and norbomene were also found to undergo hydroarylation under similar condition. [Cp IrCl2]2 catalyzes aromatization of benzoic acid with two equivalents of internal alkyne to form naphthalene derivatives via decarboxylation in the presence of Ag2C03 as an oxidant (25) [112]. 

Ahlquist, M. Fabrizi, G. Cacchi, S. Norrby, P.-O. The Mechanism of the Phosphine-Free Palladium-Catalyzed Hydroarylation of Alkynes. J. Am. Chem. Soc. 2006, 128, 12785-12793. 

Alkynes undergo stoichiometric oxidative reactions with Pd(II), A useful reaction is oxidative carbonylation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCl and CuCb in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive react ion [470]. Also efficient carbonylation of terminal alkynes using PdCk CuCl and LiCl under CO-O2 (1 1) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylation of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527[473],... 

Reetz and Sommer then studied the intramolecular hydroarylation of alkynes when they were looking for carbon triple bond coupling reactions. Depending on the substrate, the choice of gold(I) or gold(III) species was crucial [127]. 

From an atom economy perspective, He and Shi achieved efficient solventless hydroarylation of alkynes. Reaction took place efficiently under air atmosphere at ambient temperature and different functional groups could be tolerated. The catalytic system employed was AuCl3/AgTfO (1 3) and both inter-molecular and intra-molec-ular processes were described [128]. 

The cationic binuclear complex [(Mes3PAu)2Cl]BF4 has been found to catalyse the reaction of 2-methyl- or 2-pentyl-furan (78) with phenylacetylene, pent-l-yne, or hept-l-yne (79) to afford the products of a twofold hydroarylation of the alkyne (80).120... 

Scheme 1. Conventional (top) and direct (bottom) hydroarylation of alkynes.

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