Alkyne-gold hydration

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

Seheme 16.29 Water-soluble gold complexes employed in alkyne hydration. 

Scheme 16.49 Gold-promoted hydration of terminal alkynes at room temperature.

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. 

Anionic and neutral organometallic gold(III) compounds with one or two organic radicals, CeFs or (2,4,6-(CH3)3C6H2), can efficiently mediate alkyne hydration in neutral media in refluxing methanol with a catalytic activity similar to that reported for NaAuCla (Table 2) [115]. The addition of acidic co-catalysts improves the catalytic activity of this reaction. 

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. 

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]. 

Similarly, Vasudevan and Verzal have found that terminal alkynes can be hydrated under neutral, metal-free conditions using water as solvent (Scheme 4.15) [41], While this reaction typically requires a catalyst such as gold(III) bromide, employing microwave-superheated distilled water allowed this chemistry to proceed without any catalyst. Extension of this methodology led to a one-pot conversion of alkynes to imines (hydroamination). 

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]. 

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). 

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 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... 

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. 

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... 

Catalytic conversions of allenes are sometimes considered models for catalytic reactions of alkenes, even though allene reactivity is more closely comparable to that of alkynes rather than alkenes. The catalytic hydration of allenes was achieved by means of a cationic gold(I) complex with a carbene steering ligand, (IPr)AuCl/ AgOTf (5 mol%), in dioxane (rt, 4—9 h) in fair yield [180]. Attack of water is selective for the terminal carbons, whereas regioselectivity in nonsymmetric substrates is controlled by steric, electronic, and solvation factors. 

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. 

A variety of gold(I) complexes containing the water-soluble phosphine ligands TPPMS, TPPDS, and TPPTS were found active catalysts for the hydration of phenylacetylene to acetophenone in aqueous media. The isolated [Au(C=C Bu)(TPPTS)] showed a very high activity (1000 h ) at refiux temperature in methanol/water 5 1 in the presence of 10 mol% H2SO4 as cocatalyst (224). Similarly, various water-insoluble [AuBralNHC)] (225) and water-soluble [AuCl(NHC)] complexes (226) were effective in hydration of various terminal alkynes to the corresponding 2-oxo-derivatives. 

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 16.48 Hydration of alkynes catalysed by well-defined gold-phosphine species at room temperature.

In 2003, Herrmann reported the hydration of alkynes with a NHC-Au compound. This was the first catalytic application involving NHCs in gold... 

Ruthenium complexes are often inexpensive, readily available, and active catalysts for the hydration of alkynes [177-179]. In contrast to most mercury and gold systems, several of the Ru-based catalysts displayed a propensity to generate the anti-Markovnikov hydration products. One of the more practical approaches to this anti-Markovnikov hydration chemistry was developed by Herzon (Scheme 2.115) [180]. His approach entailed the use of a ruthenium compound bearing a 5,5 -(bistrifluoromethyl)-2,2 -(bipyridine) as the supporting ligand. A variety of ruthenium complexes could be isolated, and at least one... 

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

Christophe Darcel of the Universite de Rennes I developed (Adv. Synth. Cat. 2009, 351, 367) an inexpensive Fe catalyst for the hydration of a terminal alkyne 3 to the ketone 4. Carlos Alonso-Moreno and Antonio Otero of the Universidad de CastiUa-La Mancha devised (Ady. Synth. Cat. 2009, 351, 881) a Rh catalyst for the complementary hydration of a terminal alkyne 5 to the aldehyde, by way of the imine 7. Internal alkynes often give mixtures of ketones on hydration, but Bo Xu and Gerald B. Hammond of the University of Louisville found J. Org. Chem. 2009, 74,1640) a gold catalyst that converted an alkynyl ester 8 into the y-keto ester 9. 

Copper complexes containing abnormal imidazolylidene 4 were successfully applied to the [3+2] dipolar cycloaddition of azides and alkynes. " Related abnormal imidazolylidene gold(i) complexes showed good activity in the hydration of alkynes. However, the precursor complex required activation with a silver salt, which is likely to lead to carbene transfer (see Section... 

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