Gold-Catalyzed Nucleophilic Additions to Alkynes

Gold-catalyzed nucleophilic addition to alkynes are operationally safe and simple to perform, and do not generally require rigorously inert reaction conditions. 

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]. 

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. 

Also in the activation of alkynes for nucleophilic attack, gold salts prove to be soft, exceptionally carbophilic Lewis acids, as confirmed by the examples shown in Scheme 3 [10]. According to Utimoto and Fukuda both the addition of water as well as of amines to alkynes are catalyzed by gold(III) salts, in particular by sodium tetrachloroaurate ketones such as 8 and imines such as the ant toxin 10 are obtained as products in excellent yields [10a-e]. In the cyclization reaction giving the 1,4-dioxane 12 developed by Teles et al.,... 

Gold(III)-catalyzed addition of oxygen nucleophiles to alkynes ... 

Gold(I)-catalyzed addition of oxygen nucleophiles to alkynes (h) J. H. Teles, S. Brode,... 

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. 

Abstract Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonacti-vated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes. 

The gold-catalyzed inter- and intramolecular addition of carbon- and heteronucleophiles to alkynes leads to a wide variety of products [6]. In the case of nitrogen nucleophiles, the addition of amines, anihnes [67, 68], imines [69], pyridines and azides [72] is possible (Scheme 1.1). 

Mechanistically, formation of products of exo-trig and endo-tng cyclization can be explained by the attack of the nucleophiles to cyclopropyl gold(l) carbene intermediates XXVI at carbons a or ft to form products 86 or 87 (Scheme 47), similarly to that found for Pt(ll) ([235], an example of gold-catalyzed methoxycy-clization of an allenene [237]). In the first step, the alkene reacts with the alkyne-gold(I) complex in an electrophilic addition process. 

Other nucleophiles that have been used in this context are acetylides (alkynes). The addition of those to iminium cations generated in situ from aldehydes and secondary amines accomplishes a gold(III)-catalyzed three-component coupling for the synthesis of propargylamines, as can be observed in equation (124). The reactions are performed in water or in tetrahydrofuran (THF) when supported catalysts are employed.Chiral prolinol derivatives as... 

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