Gold endo-cyclization

The formation of these products can be rationalized as shown in equation (46). Thus, upon complexation of Au(I) to the aUcyne in the reacting enyne, an endo cyclization occurs to form a cyclopropyl gold carbene, which can be trapped by a nucleophile. However, the lack of stereospecificity observed in some of these reactions, suggests the formation of open six-membered ring cations as intermediates, which can be intercepted by an O-Boc group.3-Hydroxy-1,5-allenynes react similarly with Pt(II) catalysts. ... 

Shin has reported the gold(III)-catalyzed 5-endo cyclization of tert-butyl allenoates to form 2,4-disubstituted butenolides [116]. As an example, treatment of terf-butyl 2-benzyl-5-phenyl-2,3-pentadienoate with a catalytic amount of AUCI3 in dichloro-methane at room temperature for 1.5 h led to isolation of the butenolide 78 in 96% yield (Eq. (12.42)). The protocol tolerated a range of substitution at the allenyl carbon atoms. 

In the total synthesis of (+)-lycopladine A by Toste et al. [30], a gold-catalyzed 5-endo cyclization of an iodoalkyne with a silyl enol ether has been used (Scheme 16.25). This transformation efficiently produces a -unsaturated bicyclic ketone that possesses the required quaternary asymmetric center at the position a to the carbonyl group. The vinyl iodide functionaiity generated during the cyclization was subsequently used in a palladium-catalyzed cross-coupling reaction in order to construct the pyridine ring of (-F)-lycopladine A. 

A gold-catalysed cyclization of 3-(2 -azidoaryl)-l-arylpropargyl carbonates to quinolines has been reported to occur via a 3,3-rearrangement, 6-endo-trig cyclization, and denitrogenation (Scheme 4). ... 

Nieto-Oberhuber, C., Munoz, M. R, Bunuel, E., Nevado, C., Cardenas, D. J., Echavarren, A. M. (2004). Cationic gold(I) complexes highly alkynophilic catalysts for the exo- and endo-cyclization of enynes. Angewandte Chemie - International Edition, 43,2402-2406. 

Carbocyclization of 1,5- and 1,6-diynes has been reported leading to benzopyrones [142] and Z-cyclopentylidenes [143, 144], respectively. Furthermore, 1,4-diynes 44 react in the presence of gold-catalysts to form seven-membered ring heterocycles 45 by an endo-cyclization (Scheme 18) [145]. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

IH of 2-alkynylanihnes has been also studied in the presence of molybdenum [284], palladium [276, 277, 281], and gold catalysts [276]. It provides indoles in low to good yields as a result of 5-Endo-Dig cyclizations (Eq. 4.73) [277]. 

Selective activation of alkyne functions of enynes to give products either of alkoxy-cyclization or of exo- and endo-skeletal rearrangement can be achieved by using alkynophilic cationic gold(I) complexes. The endocyclic cyclization catalysed by gold(I) proceeds via a mechanism different from those known for Pd(II), Hg(II), or Rh(I) catalysts.118... 

With gold(III), no conversion was observed (Table 12.16, entry 1) the coordina-tively saturated gold complex gave a low yield of the 6-endo-dig cyclization product (entry 2). The cationic gold complex with a free coordination site gives an excellent yield with the same selectivity (entry 3) the same is true for AgSbF6 alone (entry 4). But this is not true for all silver catalysts with a systematic increase in the pK.A value of the conjugate acid of the silver counterion, increased portions of the 5-exo-dig product were produced (entries 5 and 6). 

A gold(I)-catalyzed domino reaction sequence involving pentenynyl tosylamides led to the formation of 2,3-disubstituted pyrroles containing a quaternary center in the 2-substituent <07OL3181>. The mechanism of the reaction involved a 5-endo-dig cyclization followed by an aza-Claisen rearrangement. 

The first gold-catalyzed addition reactions of carbon nucleophiles to allenes were only first disclosed in 2006, and the number of examples is still small. Toste and co-workers showed that allenic silyl enol ethers undergo a 5-endo- ng cyclization to hexahydroindenone derivatives in the presence of a cationic gold catalyst (Scheme 4-10). In these transformations, water or methanol is used as an external proton source for protodeauration of an intermediate vinylgold species. In an analogous manner, cyclopentenes were obtained in good yields from allenic P-ketoesters. In the presence of a palladium catalyst and an allylic halide, these substrates afford functionalized 2,3-dihydroflirans. 

A further example for a metal-initiated reaction sequence providing an indole-inspired NP-based complex scaffold was reported by Van der Eycken and coworkers [7]. In this case, a Ugi reaction provided the desired substrate for the sequence of cyclization reactions initiated by the activation of the acetylene with a gold catalyst. The Ugi four-component reaction employed the indole-carboxaldehyde 12, the nitrile 13, amine 14, and carboxyhc acid 15 and led to the formation of the intermediate 16. In the presence of a gold(I) catalyst, instead of the expected indoloazepinone that could be formed via an endo-dig cyclization, a tetracyclic spiroindoline 17 was formed diastereoselectively (Scheme 13.3). 

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