Cyclizations gold

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]. 

As can be seen in the scheme below, the catalytic activity of gold species was also shown in a multi-substituted furan synthesis. Cyclization of allenones in the presence of Au(III)-porphyrin gave rise to the corresponding substituted furan in good to high yields. The catalyst can be recycled several times and still maintain the same catalytic activity <06OL325>. 

Cyclization of. V-alkeny lam ides to 2-oxazolines was achieved in very mild conditions with fert-butyl hypoiodite <06OL3335>. The 5-exo-dig gold(I)-catalyzed cyclization of propargylic trichloroacetimidates 129 proceeded with remarkably efficiency under very mild conditions to give 4-methylene-4,5-dihydrooxazoles 130 in good yields. The mildness of the protocol was clearly responsible for the lack of isomerization of the final products to the corresponding, thermodynamically more stable, oxazoles <06OL3537>. 

Hypothetical (carbene)gold(i) structures of intermediates and reaction coordinates have been calculated (B3LYP/ 6-31G and LAN2DZ levels) for (H3P)Au+-catalyzed cyclization reactions of terminal enynes. The endocyclic skeletal rearrangement reactions were found to proceed exclusively via cyclopropylcarbene complexes.240... 

In contrast to the palladium-catalyzed reactions, little attention has been paid to other transition-metal catalysts. Recently some efficient reactions using copper(i or 11), gold(m), platinum(n), and tungsten(O) have been developed for the synthesis of nitrogen-heterocycles. The copper-catalyzed cyclizations of 2-alkynylaniline derivatives into... 

Whereas Gold and Sghibartz showed that cation complexation depressed the rate of crown-ether disrupture, there is convincing evidence that crown ether formation is facilitated by the presence of cations. The template effect, presumably due to complexation of the open-chain precursor and formation of a crown-type conformation, clearly emerged from studies in which the yield of crown ethers was related to the type of cations present (Reinhoudt et al., 1976). Kinetic evidence for the template effect was presented by Mandolini and Masci (1977), who showed that the rate of cyclization of the precursor of benzo-18-crown-6 [2061 decreased in the order Ba2+ > SrJ+ > K+ > Na+ > Li+. This sequence is the same as the one found for the stability constants of the 1 1 complexes of these cations with 18-crown-6 in water (Table 3). 

Tertiary N-butynylamine 48 when oxidized generates an N-oxide intermediate that is cyclized in situ via gold catalysis to give bicyclic piperidone 49 (09JA8394). As amine 48 can be prepared readily, the overall transformation constitutes a formal [4+2] synthesis. 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

Hydroamination of Allenes Different related amines can also be cyclized. The use of free amino groups led to long reaction times (several days), but sulfonamides, acetyl or BOc as protecting group led to fast conversion (in the latter case, problems of diastereoselectivity were observed). Optimization studies showed that, although cationic gold (I) complexes were not effective for these conversions, AuCI was a very good catalyst for these reactions. 

Alcohol addition was also studied by Hashmi et al. in intramolecular processes [28]. Through gold catalyzed cyclizations of (Z)-3-ethynylallyl alcohols 157, these authors were able to obtain furans 159. Reaction occurred via intermediate 158, which tautomerized the heteroaromatic furan, which is thermodynamically more stable (Scheme 8.15). 

Krause and Belting studied a tandem catalyzed reaction, in this case intramolecular cyclization and intermolecular hydroalkoxylation. The substrates were various homo-propargylic alcohols in the presence of non-tertiary alcohols and a dual catalyst system consisting of Br( >nsted acids and a gold precatalyst (Equation 8.43). 

Sames et al. studied the cyclization of phenyl/propargyl ethers catalyzed by different metal salts since this Friedel-Crafts alkenylation had previously been reported to be catalyzed by metals such as Pd, Zr In and Sc [122-124] or even zeolites by hereogeneous catalysis [125]. In this preliminary research, the maximum yield of the desired product achieved by gold was only 6%, the best results being obtained with PtCl2 as catalyst [126]. 

For the synthesis of furanones, Kirsch et al. studied the gold-catalyzed hetero-cyclization/1,2-migration cascade reaction of a-hydroxy propargyl ketones [139]. 

In a recent report, Toste and Shen developed a gold(I)-catalyzed cyclization of alkynes using silyl ketene amides that, by means of prior hydrolysis, provided 1,6-enyne (285) or 1,5-enyne systems (287) activated for the intramolecular cycloisomerization [160]. 

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... 

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