Alkyne-gold intramolecular

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]. 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

The reaction worked with both internal and terminal alkynes (except silylated alkynes) and in many solvents, even in the neat alcohol added [105]. The mechanism proposed involved two catalytic cycles first, gold catalysis would lead to dihydro-furan by a fast intramolecular reaction then, the subsequent slower intermolecular reaction would be produced by the addition of alcohol to the enol ether to deliver a ketal (Scheme 8.18). 

Indenyl ethers were synthesized via intramolecular carboalkoxylation of alkynes. In this process, a benzylic ether group played a nucleophile role to capture a vinyl gold intermediate obtained by alkyne activation. The first catalytic system tested by Toste and Dube in this study was a mixture of [AuClPPh3] and AgBF4. However, the moderate yield prompted them to research the use of more electrophilic gold(I) complexes such as [AuP(p-CF3-C6H4)3]BF4, which increased the yield of cydized products by 70% [107]. 

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

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]. 

In a recent report, Toste and Shen developed a gold(I)-catalyzed cyclization of alkynes using silyl ketene amides that, by means of prior hydrolysis, provided 1,6-enyne (285) or 1,5-enyne systems (287) activated for the intramolecular cycloisomerization [160]. 

Other 1,3-acyl migrations of propargylic carboxylates catalyzed by gold give intermediate allenes, which can afford heterocyclic compounds by intramolecular attack of the appropriate nucleophiles. The intermediate allenes formed by 1,3-acyl migrations can also react intramolecularly with alkynes to form naphthalenes, although this reaction proceeds more efficiently with Ag(I) catalysts, and is discussed in the aUcyne-carbon nucleophile section. 

Additional evidence for the involvement of metal carbenes in these processes was obtained in the reaction of dimeric substrates with a cationic Au(I) catalyst to give disubstituted alkynes (equation 39). These reactions can be explained by isomerization of the initially formed cyclopropyl gold carbene by a [1,3] metallotropic shift, followed by intramolecular trapping of the gold carbene by the alkene. Other examples of [1,3] metallotropic shifts in gold chemistry have been observed recently. ... 

Michael additions to conjugated carbonyls can be catalyzed by gold species. Among them, arene additions are the most studied area but other nucleophiles can attack the gold-coordinated enones as well. In fact, the intermolecular aza-Michael additions of carbamates to enones was reported in 2002 with both Au(I) and Au(III) salts, and in 2007 an intramolecular aUcoxide and amide conjugate addition has been developed and applied to the synthesis of (+)-andrachcinidine (equation 132). In the latter case, the enones are formed as intermediates in a previous gold-catalyzed step that is the hydration of an alkyne and methanol loss. Then the cyclization takes place to give piperidines. 

The reaction has been done with a palladium catalyst, a titanium catalyst, a tantalum catalyst,and with a gold catalyst. An intramolecular addition of amines to an alkyne unit in the presence of a palladium catalyst generated heterocyclic or cyclic amine compounds.The titanium catalyzed addition of primary... 

The formation of an arene oxide intermediate, exemplified below, during the gold-catalyzed intramolecular reaction between furans and alkynes to form phenols was observed experimentally for the first time <05AG(I)279. ... 

A synthesis of 181, a venom alkaloid of Solenopsis [454], was reported in which the tetrahydropyridine ring was formed in an intramolecular amine addition to an alkyne, catalyzed by a gold (III) salt [455],... 

The nucleophilic addition of alcohols to alkynes was reported by Utimoto with NaAuCU and later by Teles with cationic gold complexes.The enol ethers formed can be hydrolyzed to form carbonyl compounds or trapped as ketals (equations 4 and 5). An intramolecular version of this reaction was reported by the group of Genet to give bicyclic ketals (equation On the basis of this concept, a glycosidation... 

For alkynes (and in part, allenes), synthetically useful protocols for Markovnikov and anti-Markovnikov selective hydrations, hydroalkoxylations (mainly intramolecular), and hydrocarboxylations are available and find increasing applications in organic synthesis. In the past decade, the research focus on cationic gold(l) complexes has led to new additions to the catalysis toolbox. It can be predicted that a further refining of such tools for alkyne functionalization with respect to catalytic activity and functional group tolerance will take place. 

Gold-catalyzed intramolecular [4+2] cycloaddition of furans with alkynyl substituents led to the formation of phenol derivatives, A mechanistic study showed that a transposition of the oxygen from the carbon atoms of furan to the former terminal carbon of the alkynes seemed to occur through an intramolecular mode and the epoxide depicted below was presumably an intermediate <01OL3769>. 

The intermolecular hydroarylation of indoles or pyrroles with alkynes in the presence of cationic gold(I) catalysts leads to 2 1-adducts With (Z)-2-en-4-yn-l-ols as an unsaturated reaction partner, indoles are converted into dihydrocyclohepta[ )] indoles in a one-pot reaction sequence that involves a gold-catalyzed intermolecular Friedel-Crafts alkylation followed by an intramolecular hydroarylation (Scheme 4-9). ... 

Another cycloisomerization pathway of 1,6-enynes involves intramolecular cyclopropanation of the alkene by the alkyne (Scheme 4-24). This reaction is favored for enynes bearing a cyclic olefin and probably proceeds by 6-encto-dig-cyclization, followed by proton loss and protodeauration of the gold carbene... 

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