Alkynes gold -catalyzed hydration

Representative procedure for the gold-catalyzed hydration of alkynes. Octan-4-onf ... 

Gold-catalyzed hydration of alkynes has been applied in the total synthesis of pterosines B and C (Scheme 11) [125], a class of sesquiterpene indane derivative that possesses interesting biological activity. 

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]. 

Other cations (Cu2+, Pd2+, Ru3+, Ni2+, Rh3+) incorporated into Nafion-H have been found to promote hydration.36 Other metals that catalyze hydration of alkynes include gold(III),37 ruthenium(in),38 and platinum(II) (Zeise s salt39 40 and halides40), p-Methoxybenzenetellurinic acid is very effective in the hydration of terminal alkynes 41 Similar to the hydration of alkenes, photochemical acid-catalyzed hydration of alkynes is possible ... 

The first examples of hydration of alkynes catalyzed by gold salts were reported in 1976 by Thomas." Later, Utimoto found that the reaction could be carried out with lower amounts of catalyst." Tanaka and coworkers reported a general hydration of alkynes using cationic Au(I) complexes generated in situ by protonolysis of [AuMe(PPh3)] as depicted in equations (2) and (3). Markovnikov-type addition is observed in all cases. Other complexes of Au(I) and Au(III) have proved to be effective in this reaction. The somewhat related gold-catalyzed addition of HCl to alkynes is an industrial process for the generation of vinyl chloride. " ... 

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 aldehyde component has also been replaced by diethyl formylphosphonate hydrate in the silver-catalyzed synthesis of V-PMP-protected a-aminopropargylphospho-nates [139] and by 2-oxoacetic acid [140] or glyoxylic acid [141] in copper-catalyzed microwave-assisted decarboxyla-tive three-component couplings. In addition, glyoxylic acid has been coupled with amines and alkynes in the gold-catalyzed synthesis of butenolides (see Scheme 3.48) [121]. 

SCHEME 2.114 Gold-catalyzed Markovnikov hydration of alkynes using low catalyst loading [175]. 

Gold-Catalyzed Hydrofunctionalization of Ti-Bonds 2.1 Hydration and Hydroalkoxylation of Alkynes... 

The hydration of alkynes is also accomplished by use of catalytic amounts of palladium and gold salts.305 The mildness of this reaction is demonstrated by the preparation of 5-oxo-prostaglandin derivatives (equation 202). In this connection, it should be noted that attempted use of other metal salts to catalyze C—-C triple bond hydrations has met with little success.306... 

Nolan and coworkers applied cationic gold(l) complexes of N-heterocyclic carbenes at elevated temperatures in the catalytic hydration of terminal and internal alkynes at very low catalyst loadings of 1,000 ppm (0.1%) down to 10 ppm (0.001 %). The thermal stability of the gold(l) carbene complex appears to be critical to achieve those results [123] (Scheme 21b). Iron Iron(III) chloride catalyzes... 

Two mechanistic hypotheses are considered when furans are formed via the alkyne hydration reaction (Scheme 20.1). Density functional theory (DFT) calculations for gold(l)-catalyzed furan formation were performed, and these calculations indicate that the keto pathway is preferred over the enol pathway. 

An intramolecular version of alkyne hydration was reported in 2006 by Belting and Krause [127] providing an efficient route to tetrahydrofuranyl ethers 32. This transformation consists in a tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols 31 in the presence of an alcohol in a dual catalyst system (a gold precatalyst and a Bronsted acid) under mild conditions (Scheme 13). The reaction proceeds satisfactorily with terminal and internal alkynes, with bis-homopropargylic alcohols and alkynyl phenols to provide cyclic acetal skeletons that occur in a variety of natural products. Substituted furanones can be obtained by gold(III)-catalyzed activation of alkynes by heterocyclization and subsequent 1,2-alkyl shift [128]. 

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