Triple cycloisomerization

Palladium catalyzed cycloisomerizations of 6-cn-l-ynes lead most readily to five-membered rings. Palladium binds exclusively to terminal C = C triple bonds in the presence of internal ones and induces cyclizations with high chemoselectivity. Synthetically useful bis-exocyclic 1,3-dienes have been obtained in high yields, which can, for example, be applied in Diels-Alder reactions (B.M. Trost, 1989). 

The key step in the gold-catalysed cycloisomerization of enynes (75) is believed to be the nucleophilic attack at the Au-coordinated C=C triple bond to form a vinylic gold intermediate (76) that is eventually converted into the final product (77).119... 

It must be pointed out that tungsten [22-26] and molybdenum [26-29] carbonyl precursors also have remarkable catalytic activity in the cycloisomerization of alky-nols to produce dihydropyrans and dihydrofurans via intramolecular nucleophilic addition of the hydroxy group to the terminal carbon of the triple bond, activated... 

Even the propargylic alcohol derivative 35 with an electronically almost unactivated triple bond smoothly undergoes palladium(0)-catalyzed cycloisomerization to give an 85% yield of the allylic alcohol, (3/ , 3a5 )-3-cyclohexyl-4-methylene-3,3a,4,5-tetrahydro-lff-cyclo-penta[c]furan-6-methanol (36)." The substrate molecule containing a rer/-butyldimethylsilyl substituent at the alkyne instead of a hydroxymethyl group, however, again failed to undergo the cycloisomerization, presumably due to steric hindrance. ... 

For cycloisomerization of a-alk3myl-p-keto esters the use of Tf2NAu in conjunction with very bulky tris[(triarylsilyl)ethynyl]phosphine hgands, remarkable rate enhancements are observed. The effect is attributable to the cavity environment created by the ligand to keep the nucleophilic center and the Au-activated triple bond of the substrate close. 

Transformation of 1,2,4-aIkatrienes into cyclopentadienes is catalyzed by PtCl2 at room temperature. Cycloisomerization to break up an acetal unit and re-add the 0/C bonding partners to a conjugated triple bond has been observed. 

The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO2H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45]. Most importantly, oxidative addition of AcOH to Pd(0) generates H-Pd-OAc 143, and the cyclization of 1,6-enynes starts by insertion of the triple bond to 143 to afford the alkenylpalladium 144. Subsequent intramolecular insertion of the double bond gives the alkylpalladium 145. The termination step is (i-R elimination and either the diene 136 or 138 is formed with regeneration of H-Pd-OAc. It should be noted that the alkenylpalladium 144 is a similar species formed in a Heck reaction by oxidative addition of alkenyl halide to Pd(0). Based on this reaction, alkyne is a useful starter in domino cyclization of polyenynes. 

A double cyclization of an aldehyde enol to the methylene malonate, followed by a cycloisomerization onto the triple bond, leads to a bicyclo[5.3.0] decane of a tris-norguaiane (Scheme 10) [45]. 

The Conia-ene reaction of P-ketoesters bearing a pendant triple bond involves the cycloisomerization of an enyne formed by enolization. This transformation is efficiently catalyzed by cationic gold(I) complexes and afforded cyclopentane derivatives with excellent yields and moderate to good diastereoselectivities (Scheme 4-40). Acetylenic silyl enol ethers or imines react in an analogous manner. By this method, iodoalkynes were converted into iodocyclopentenes, which are highly useful in natural product synthesis. 

The ene reaction, or Alder-ene reaction, is a cycloisomerization involving the migration of an atom, typically hydrogen, across two nonconjugated double or triple bonds (Scheme 11.70). The reaction often requires high temperatures or the addition of strong Lewis acids. 

Abstract The cycloisomerization of enynes can be performed with a variety of catalytic systems which operate according to various types of activation process. Metal catalysts showing different activation abilities can promote as the first step either oxidative coupling, triple bond insertion into metal-hydride bond, allylic activation, electrophilic activation, metal-vinylidene formation, and [2+2]-cycloaddition (metathesis). Depending on the nature of the enyne and the catalytic system, all these processes lead to a variety of cyclic compounds. 

A rhodium-catalyzed cycloisomerization reaction of triyne 137 to 141 involves cleavage of the C=C triple bond (Scheme 7.49) [68]. The following reaction pathway is proposed initially, oxidative cyclization produces the rhodacycle 138, which then undergoes reductive elimination. The rhodium cyclobutadiene complex 139 is thus generated, and then undergoes oxidative addition to produce the rhodacycle 140. This isomerization from 138 to 140 would reduce the steric congestion of the heUcal structure. Subsequently, a cycloaddition reaction between the rhodacycle and the pendant alkyne moiety takes place to afford 141. 

The reactions of propargylic aziridines with a platinum catalyst in aqueous media led the cycloisomerization of aziridines 39 forming pyrroles 40 (Scheme 13) [45]. According to the proposed mechanism, the platinum coordinates with carbon-carbon triple bond that is followed by attack of the aziridine nitrogen on the alk5me forming a pyrrolyl-platinum species, which undergoes aromatization to form the final pyrrole products. 

Having demonstrated the feasibility of triple cycloisomerizations, synthetic schemes were once again developed that replaced the terminal benzene moieties with biphenylene, giving rise to 32 and 34, respectively. The former then provided... 

Numerous linear and angular [A/]-phenylenes can be obtained rapidly by this methodology [72], For example, the C3/i-symmetric [7]-phenylene 134 has been synthesized via cobalt-mediated triple cycloisomerization of a nonayne (Figure 1.5) [73]. The syn and anti double bent [5]phenylenes 135 and 136 have been assembled via double cobalt-catalyzed cycUzation of hexaynes [74], Helical [7]-, [8]-, and [9]phenylenes (heliphenes) such as 137 have also been prepared via cobalt-mediated multiple cycloisomerization of polyynes [75]. 

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