Gold -activated alkynes

As shown in Table 11 and Scheme 112, a C-H bond of terminal alkynes is activated by an Au(i) species producing gold acetylenide intermediates, which react with immonium ions generated in situ from aldehydes and secondary amines to provide propargylamines in high yields. This reaction proceeds in water with 1 mol.% of Au(i) or Au(m)... 

Hydration and Hydroalkoxylation of Alkynes Gold compounds were first applied to catalyze these types of reactions by Utimoto et al. in 1991, when they studied the use of Au(III) catalysts for the effective activation of alkynes. Previously, these reactions were only catalyzed by palladium or platinum(II) salts or mercury(II) salts under strongly acidic conditions. Utimoto et al. reported the use of Na[AuCI41 in aqueous methanol for the hydration of alkynes to ketones [13]. 

The proposed reaction mechanism is shown in Scheme 6.75. The nitroalkene moiety of bifunctional ortAo-alkyne-substituted nitrostyrenes 159 is activated through hydrogen bonding with catalyst 160 to incorporate the stereoehemieal information in the first AFC reaction. Then the alkyne is activated under gold catalysis to affect the seeond AFC/ring expansion cascade. 

The synthesis of benzo[f ][l,4]diazepines 66 by a tandem hydroamination-cychzation sequence was carried out using a gold(I)-N-hetereocyclic car-bene catalyst (14JOM438). The authors utilized readily available N-alkyl o-phenylenediamines 63 and arylacetylenes 64 as starting materials. They proposed that the reaction proceeds by amination of a gold-activated alkyne with subsequent cyclization of intermediate 65. 

Intermolecular [2+2]-cycloadditions of alkenes with alkynes are catalyzed by cationic gold(I) catalysts of type G and afford cyclobutenes in high yields and regioselectivities. Because of the steric demand of the catalyst, the alkyne is activated selectively, and competing pathways (including coordination to the alkene) are suppressed. The reaction proceeds well with alkynes bearing either electron-rich or electron-poor substituents. The corresponding 6is-cyclobutenes were obtained from 3- or 4-diethynylbenzene. 

The reactions described below are categorized according to the nature of the nucleophile that attacks the gold-activated alkynes/ allenes. While complex 1 is emphasized, other cationic Au(I) complexes could in general catalyze these reactions as well. 

Gold(l) complexes exhibit excellent chemoselectivity towards C-C Ti-systems. Although [AuL]" does not selectively coordinate alkynes over other rr-systems, alkynes are activated selectively because the nucleophile attack is thermodynamically more favored. In the context of 1,6-enynes, while the [AuL]" species indifferently coordinates to both Tu-systems, the addition occurs exclusively to the [AuCalkyne)]" complex, which has a lower LUMO than the analogous [Au(alk-ene)]" complex [63]. 

For an example, see the recent advances in platinum and gold activation of alkynes Fiirstner, A. and Davies,... 

Unlike in the case of [M(CO)6] (M = Cr, Mo, W) and certain Ru(II) complexes, which activate alkynes via vinylidene metal complexes [102, 107-111], gold complexes promote reactions of alkynes by the formation of electrophilic ri -alkyne-gold(l) complexes [1-13]. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

The cycloaddition-isomerization procedure can be accomplished in the presence of a catalytic amount of a transition metal salt. The reactions proceed at room temperature, neither air nor water needed to be excluded. The presence of an electron-withdrawing group is not necessary to activate the dienophile as the example below shows that gold coordination increases the electrophilicity of the triple bond. The presence of a terminal alkyne should also be important. In the case of a disubstituted alkyne no reaction can be observed <00JA11553>. 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

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]. 

Until 1998, only gold(III) was believed to be effective for catalyzing these processes because, as mentioned previously, only the gold(I) compound K[Au (CN)2] was tested and it was inert to catalysis. Fortunately, Teles et al. reported very strong activity in the addition of alcohols to alkynes when they used cationic gold( I) -phosphane complexes [14]. In this study, the aforementioned authors tested for the first time the suitability of nucleophilic carbenes that displayed even greater activity than other gold complexes, but they were unable to synthesize the subsequent cationic derivatives. 

The addition of water and methanol to terminal alkynes has also been studied by Laguna et al. by pentafluorophenyl and mesityl gold derivatives. Both acidic and non-acidic conditions led to high activity, even in the presence of as little as 0.5 mol% of catalyst. The use of pentafluorophenyl compounds allowed them to obtain additional spectroscopic information in the stoichiometric reaction of the complex [Au (C6F5)2C1]2 and phenylacetylene, which showed that gold(III) was the active species in the catalytic process. The reaction followed the Markovnikov rule, as shown in the proposed mechanism (Scheme 8.13), delivering the corresponding ketones or diacetal products [96]. 

In a joint study by Schmidbaur and Raubenheimer, several phosphine carboxylates and sulfonates of gold and silver were tested as catalysts for the hydration of nonactive alkynes [99]. While the gold complexes showed high activity for these reactions, analogous silver (I) complexes were not active in them. This different behavior was due to the fact that gold cations are weaker acceptors for their ligands and counterions than silver (I) cations (Figure 8.3). 

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]. 

A related work by Nakamura et al. was recently reported to show the gold-catalyzed process of aminosulfonylation, the formal addition of a nitrogen-sulfur bond to an alkyne moiety, and environmentally benign synthesis of a wide variety of 3- and 6-sulfonylindoles, present in many biologically active compounds [120]. 

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]. 

Gold has even shown its ability as a nucleophile activator in three-component reactions of terminal alkynes, aldehydes and amines [186]. In the case of chiral amines, excellent diastereoselectivities were obtained [187] (Scheme 8.29). ... 

Selective activation of alkyne functions of enynes to give products either of alkoxy-cyclization or of exo- and endo-skeletal rearrangement can be achieved by using alkynophilic cationic gold(I) complexes. The endocyclic cyclization catalysed by gold(I) proceeds via a mechanism different from those known for Pd(II), Hg(II), or Rh(I) catalysts.118... 

Also in the activation of alkynes for nucleophilic attack, gold salts prove to be soft, exceptionally carbophilic Lewis acids, as confirmed by the examples shown in Scheme 3 [10]. According to Utimoto and Fukuda both the addition of water as well as of amines to alkynes are catalyzed by gold(III) salts, in particular by sodium tetrachloroaurate ketones such as 8 and imines such as the ant toxin 10 are obtained as products in excellent yields [10a-e]. In the cyclization reaction giving the 1,4-dioxane 12 developed by Teles et al.,... 

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