Alkynes gold -catalyzed intramolecular

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

The formation of an arene oxide intermediate, exemplified below, during the gold-catalyzed intramolecular reaction between furans and alkynes to form phenols was observed experimentally for the first time <05AG(I)279. ... 

Gold-catalyzed intramolecular [4+2] cycloaddition of furans with alkynyl substituents led to the formation of phenol derivatives, A mechanistic study showed that a transposition of the oxygen from the carbon atoms of furan to the former terminal carbon of the alkynes seemed to occur through an intramolecular mode and the epoxide depicted below was presumably an intermediate <01OL3769>. 

Gin returned with an equally impressive synthesis of (-)-crambidine utilizing a variant of the aza-annulation employing thioimidate 59 with vinyl carbodiimide 60 (10JA1802). A rare gold-catalyzed intramolecular alkyne hydroamination of 61 cyclized the third ring of the core affording 62. With the core tricyclic scaffold constructed, four additional steps were required for the completion of the synthesis in a relatively straightforward manner. 

Scheme 9.18 Gold-catalyzed intramolecular rearrangement of sulfinyl alkynes according to Li and Zhang [37].

The gold-catalyzed intramolecular reaction of indoles with alkynes is also a well-known reaction. Alkynyl indole of type III can lead to the formation of azepmo[4,5-fc]indole derivatives IV, via 1-exo-dig cycUzation, or indoloazocine V, via -endo-dig cyclization (Scheme 1.9) [118, 133, 134]. 

Scheme 1.11 Synthesis of phenols via gold-catalyzed intramolecular reaction of furanes and alkynes...

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

In 2006, Liu and coworkers reported a gold-catalyzed intramolecular cycloaddition of diynes with tethered arenes 118 to synthesize l,3-dihydroindeno[2,l-c]pyran or 2,3-dihydro-l//-indeno[2,l-c]pyridinederivatives 120 (Scheme 12.52) [56]. On the basis of deuterium labeling, they believed that the first reaction step is the intramolecular arylation of one alkyne to form vinylgold(I) intermediate 119,... 

Several other rearrangements leading to the construction of complex scaffolds were developed with NHC-Au complexes as catalysts. More specifically, the gold-catalyzed intramolecular addition of an oxygenated functionality (carbonyl, epoxide, ether) on an alkyne has been largely employed to initiate various types of multi-step rearrangements [Scheme 11.17 and eqn (11.5)]. ... 

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 intermolecular hydroarylation of indoles or pyrroles with alkynes in the presence of cationic gold(I) catalysts leads to 2 1-adducts With (Z)-2-en-4-yn-l-ols as an unsaturated reaction partner, indoles are converted into dihydrocyclohepta[ )] indoles in a one-pot reaction sequence that involves a gold-catalyzed intermolecular Friedel-Crafts alkylation followed by an intramolecular hydroarylation (Scheme 4-9). ... 

The gold(I)-catalyzed intramolecular Schmidt reaction of azido alkynes 49 provides easy entry to a series of pyrroles 54 with a variety of substitution patterns. The proposed mechanism involves gold(I)-induced activation of the alkyne toward addition by the proximal nitrogen of the azide. Subsequent loss of nitrogen leads to cationic intermediate 52, which is... 

The sequential intramolecular hydroarylation of alkynes is applied to the synthesis of structurally complex extended x-systems. The gold-catalyzed sequential intramolecular hydroarylation of triynes followed by aromatization with DDQ proceeded to give triaryl-substituted diacenaphtho[l,2-y l, 2 -l] fluoranthenes, which can be used for organic light-emitting devices (Scheme 21.49) [55]. 

Very recently, the enantio- and diastereoselective synthesis of an S-shaped double azahelicene has been achieved via the gold-catalyzed sequential intramolecular alkyne hydroarylation (Scheme 21.51) [57]. 

The synthetic potential of gold catalysis, more especially for the generation of structural complexity, is particularly well illustrated by the total syntheses of Englerin A and B, reported independently in 2010 by Echavarren et al. and Ma et al. [31] (Scheme 16.26). A very similar approach was used by these two groups to produce, via a gold-catalyzed [2+ 2-1-2] intramolecular cycloaddition between an alkyne, an alkene, and a ketone, the core structure of the Englerins. Notably, this complex gold-catalyzed sequence, which operates with an absolute control of the stereoselectivity, allowed the creation of three new asymmetric centers and three new bonds (2 C-C and 1 C-O bonds). 

In the hydroamination of unsaturated carbon-carbon bonds, gold catalysts play an important role. Intermolecular hydroamination of alkenes [177], 1,3-dienes [204], terminal and internal alkynes [205], and allenes [206] are known to proceed smoothly in the presence of PhsP AufI) or AuCls catalyst. In addition, amino olefins also efficiently undergo intramolecular hydroamination using similar gold catalysts. He and coworkers have developed the catalytic cycloaddition of tosylated amino olefins [207], A representative example is shown in Scheme 18.35. When N-tosylated y-amino olefin (97) is exposed to a mixture of PhsP AuCl and AgOTf (5 mol% each) in toluene at 85 °C, pyrrolidine (98) is obtained in 96% yield. The gold(I)-catalyzed intramolecular hydroamination is applicable to N-alkenyl carbamates [208], N-alkenyl carboxamides [209], and N-alkenyl ureas [210], The use of microwave irradiation results in completing the hydroamination in a much shorter time than that required under thermal reaction conditions [211], The... 

In the last decade, metal-catalyzed intramolecular nitrogen addition to alkynes has been introduced as a new methodology for the preparation of pyrazole derivatives. Liu, Xu and co-workers [29] have developed a mild and efficient protocol for the synthesis of 4-fluorinated pyrazoles via gold(l)-catalyzed tandem aminofluorination of alkynes 53 in the presence of Selectfluor (Scheme 16). In all cases (except for R-=H), mixtures of 4-fluorinated 54 and nonfluorinated pyrazoles 55 (54 55=2.1 1... 

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). 

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