Gold Alkyne Activation

Cope and Sila-Cope Rearrangements Computational studies by Yates et ed. on 1,5-enynes were used to rationalize the different regioselectivities observed for the Au(I)-catalyzed addition of alcohols to the all carbon (X = C) and silyl 1,5-enynes (X = Si) as shown in Eq. (5.9) [35]. 

In related work, the groups of Ujaque and Asensio showed that the products formed in the intramolecular variant of this reaction using asymmetric aryl-heteroaryl and diaryl sulfoxides are inconsistent with the punitive gold-carbene intermediate (Eqs. (5.11) and (5.12)) [43]. in these cases, alkylation occurred exclusively at the position adjacent to the thioaryl substituent. 

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Key reaction for the production of cyclobutane 96 was the cycloisomerization of cyclopropyl enyne 95. When 95 was allowed to react with catalytic amounts of PhjPAuCl and AgBF, an 87% yield was isolated as a sole product. The reaction proceeds through a gold alkyne activation/cycloi-somerization sequence followed by the ring expansion of the... 

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]. 

Gagosz has studied a gold(I)-catalyzed process to convert various allyl pentynyl tosylamides to functionalized pyrroles under mild conditions. Alkyne activation by Au(I) triggers a nuclephilic cyclization of tosylamide to generate the presumed alkenyl gold intermediate 385 which undergoes aza-Claisen rearrangement. Aromatization followed by protodemetalation leads to the pyrrole 387. ... 

The gold-catalyzed formal cycloaddition reactions of 2-ethynylbenzyl ethers with 8-methylquinoline oxide and ethyl diazoacetate led to a skeletal rearrangement of the benzo[c]furan motif through an attack of the diazo compound on the initial oxonium species in the alkyne activation route, followed by a Roskamp-type rearrangement and ring closure (13AGE7559). 

In the field of homogeneous catalysis, electrophilic metals [palladium(II), plati-num(II), rhodium(II), iridium (I), ruthenium(II), cobalt(I), titanium(II) and gold(I)] activate alkynes under mild conditions [2-8]. When an alkyne behaves as a ligand, there are four orbitals that can participate in the bonding (Fig. 1.1) [4]. The in-plane orbitals, Try and n, are responsible for a donor interaction (M <- L donation) and a 7r-acceptor interaction (M L back-donation) respectively. The orthogonal, out-of-plane orbitals, and n , are engaged in the M <- L 7t donation and the d symmetry M L back-donation respectively. This latter interaction can be neglected, due to the weak overlap of the orbitals. 

Gold catalysts have proven to be one of the most effective catalysts for alkyne activation. A gold-catalyzed nitrogenation of alkynes for the synthesis of amino tetrazoles (54) and carbamides through C-C and C=C bond cleavages is described (Scheme 7.35) [96]. The chemoselectivity can be easily switched by the selection of the acid additives. The protocol is featured by its broad substrate scope, direct construction of high value products, easy operation under air, and mild conditions at room temperature. 

Chen Q, Zhao J, Ishikawa N, Yamamoto Y, Jin T. Remarkable catalytic property of nanoporous gold on activation of diborons for direct diboration of alkynes. Org Lett. 

In 2010, Toste s group reported the first example of a highly enantioselective polyene cyclization reaction in which transition metal-promoted alkyne activation serves as the cyclization initiating event [34], The (MeO-DTBM-BIPHEP)gold(I)-catalyzed reaction offers an efficient method for the stereoselective synthesis of polycyclic compounds... 

Recently, the Blum group showed that the synthesis of a variety of tri- and tetra-substituted olefins by gold/palladium-catalyzed addition of sp - and sp-hybridized stannanes across monoester and diester alkynes can be accomplished with complete regioselectivity and high stereoselectivity. TTie reaction is proposed to proceed via a bimetallic mechanism where a Lewis acidic gold(I) activates an alkyne toward oxidative addition across palladium(O). 

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>. 

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)... 

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]. 

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]. 

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]. 

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