Alkyne-gold hydroalkoxylation

Representative procedure for the gold-catalyzed hydroalkoxylation of alkynes. Trans-2,5-dimethyl-2,5-dimethoxy-l, 4-dioxane ... 

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]. 

A novel gold catalyzed example of three-component addition was recently reported by Shi et al. (Equation 8.44) [106]. Terminal aryl alkynes, alcohols and 2-(arylmethy-lene) cyclopropylcarbinols provided an intermolecular tandem hydroalkoxylation/ Prins-type reaction to form 3-oxabicyclo[3.1.0]hexanes from simple materials and under mild conditions, catalyzed by the system AuClPPh3/AgOTf. The proposed mechanism for this reaction is shown in Scheme 8.19. 

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. 

Gold-catalyzed organic reactions, particularly, olefin epoxydation and hydroamination or hydroalkoxylation of alkynes to give N- or O-het-... 

SCHEME 2.85 Gold-catalyzed intramolecular hydroalkoxylation of internal alkynes [125]. 

A gold-catalyzed benzylic C-H functionalization for the synthesis of IH-isochromene derivatives 34 was disclosed by Hashmi and coworkers in their study of the intramolecular hydroalkoxylation of alkynes (Scheme 12.15) [19]. A proposed mechanism for this reaction is shown in Scheme 12.16. The reaction... 

There was an explosion of work described on gold(I) and gold(lll) catalysis in the early 2000s, and its appUcatiOTi in the hydroalkoxylation of alkynes was no exception [90, 91]. Beginning with studies toward Au(l)- or Au(lll)-catalyzed synthesis of bridged acetals [92], these catalysts were soon applied to the synthesis of spiroacetals [93, 94]. This method has been widely embraced by the synthetic conununity and used in the syntheses of a variety of complex spiroacetal namral products, including the cephalosporoUdes [95], okadaic acid [96], and ushikulide A [97]. 

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

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]. 

Despite the successes of the gold-catalyzed addition of O-nucleophiles to alkynes, the corresponding catalyzed reactions involving nucleophilic addition to olefins are very limited. Mild, metal-catalyzed additions of O-H bonds across olefins have been studied for decades, and efforts to develop such processes have intensified in the last years. Results of the hydroalkoxylation of alkenes are collected in different reviews [1, 94-96, 161]. 

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