Alkynes as Substrates

Alkynes are by far the most popular and studied functional group in gold catalyzed reactions since Thomas et al. chose them for their research in 1976 [53, 84]. 

Hydrochlorination of Alkynes When Thomas and coworkers treated different alkynes in aqueous methanol with HAuC14 and observed the corresponding ketones as major products (Equation 8.28), with less than 5% of methyl vinyl ethers and vinyl chlorides, they were unaware of the fascinating treasure that was in front of them. Some of the most important types of products for gold catalysis were reported in the aforementioned study, but unfortunately at that time this process was believed to be a gold(III) oxidation process, despite the fact that the reaction achieved almost six turnovers. 

Gold(III) was identified as the most active catalyst for that process in 1985, when Hutchings recognized that the efficiency in catalyzing the hydrochlorination of ethyne to vinyl chloride (a very important industrial process that previously used mercury salts as catalysts) correlated with the standard reduction potential of the supported metal cation. That meant that the metal could be found as a transient species in the reaction [10]. 

This was the first time that anyone stated that gold catalysis is an area worthy of further research [85]. 

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]. 

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Nucleophilic addition to Pd-coordinated carbon monoxide can be ntilized to form rings containing carbon monoxide itself as a carbonyl group. Cyclic ketones, cyclic anhydrides, and lactones are advantageously prepared in this way using alkenes and alkynes as substrates. Carbon dioxide has been found to exert an important role in the carbonylation of alk-l-ynes under water shift conditions by causing the formation of unsaturated lactones to shift toward maleic anhydrides. 

The reaction has been extended to internal alkynes as substrates (Scheme 1.44) [12]. Under slightly milder conditions, almost full conversion was noted. Most of the a,P-unsaturated aldehydes formed were obtained in good to excellent yields. Interestingly, with the terminal alkyne 1-octyne, a-hexyl acrolein was obtained only in 17% yield. In unsymmetrically substituted alkyl-aryl-alkynes, the formyl group was predominantly linked to the neighboring aryl substituent. Bulky alkyl groups forced the C-C bond formation reaction in the P position. 

Morimoto [20] extended the scope of the formaldehyde-based hydro-formylation to alkynes as substrates, where in a double carbonylation step, a,P-butenolides were formed in up to 98% yield finally (Scheme 3.8). The reaction mediated by the water-soluble TPPTS (trisodium salt of 3,3, 3"-phosphinidynetris(benzenesulfonic acid)) rhodium catalyst was conducted in water. For increasing the solubility, a surfactant was added. Noteworthy, the use of dppp (l,3-bis(diphenylphosphino)propane) instead of TPPTS resulted in a serious decrease in the yield. Formalin gave higher yields than paraformaldehyde or syngas (CO/H2 = 1 1,1 atm). 

Hexacarbonyldicobalt complexes of alkynes have served as substrates in a variety of olefin metathesis reactions. There are several reasons for complex-ing an alkyne functionality prior to the metathesis step [ 125] (a) the alkyne may chelate the ruthenium center, leading to inhibition of the catalytically active species [125d] (b) the alkyne may participate in the metathesis reaction, giving undesired enyne metathesis products [125f] (c) the linear structure of the alkyne may prevent cyclization reactions due to steric reasons [125a-d] and (d) the hexacarbonylcobalt moiety can be used for further transformations [125c,f]. 

When thiols are added to substrates susceptible to nucleophilic attack, bases catalyze the reaction and the mechanism is nucleophilic. These substrates may be of the Michael type or may be polyhalo alkenes or alkynes. As with the free-radical mechanism, alkynes can give either vinylic thioethers or dithioacetals ... 

The hydrothiolation of terminal alkyl alkynes with 96 (Fig. 2.17) proceeds with good degree of regio- and chemo-selectivity, especially with thiophenol and p-methoxy-thiophenol as substrates. Isomerisation to the internal alkenyl thiolates accounts for less than 9% of the thiolated products under the reaction conditions. In addition, further hydrothiolation of the vinyl thioether product is not observed. Typical conversions of 70-85% at 1 mol% loading at 80°C within 5 h are observed. Arylthiols substituted with electron-withdrawing groups afford lower conversions. 

The combination of Ni(COD)2/NHC complexes with EtaSiH as the reducing agent has also proved to be effective in inter molecular couplings of aldehydes and alkynes (Scheme 9) [21]. A broad range of substrates underwent couplings, including aromatic, non-aromatic, and terminal alkynes as well as branched, unbranched, and aromatic aldehydes. The regioselectivity with... 

Instead of alkynes, allenes can also be used as substrates in this type of approach. Finally, one can also apply carbon-nucleophiles such as butadienes in this domino process. Thus, Lu and Xie [145] have treated the alkyne 6/1-303 with an aryl halide 6/1-304 and an amine 6/1-305 to give the substituted pyrrolidinone 6/1-308 via the proposed intermediates 6/1-306 and 6/1-307. As a side product, 6/1-309 is found to have been formed by a cycloaddition of 6/1-303 (Scheme 6/1.81). 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

Chung and coworkers [280] combined a [2+2+1] with a [2+2+2] cycloaddihon for the synthesis of multi-ring skeletons, angular triquinanes, and fenestranes. For the preparation of tetracyclic compounds such a 6/4-17, these authors used diynes as 6/4-16 and CO as substrates (Scheme 6/4.5). Fully substituted alkynes gave low yields, and 1,5- as well as 1,7-dialkynes, did not react... 

Similar to Cp2TiCl2, T OPr1) as a less expensive precursor, can also be utilized for the synthesis of titanium-alkyne complexes.13 The reactivity of the (Pr10)2Ti-alkyne complexes toward a variety of substrates has been investigated.14 In the case of unsymmetrical alkynes as a starting material, the less hindered carbon of the resultant... 

As expected, the decrease in the initial alkyne concentration results in less dimerization and higher initial hydrogenation rates. A similar substrate-inhibition effect has also been observed with PhC CH as substrate, revealing a complex dependence of the hydrogenation rate upon the alkyne concentration. To the best... 

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