Enyne cycloisomerization proposed mechanisms

The proposed mechanism of the above cycloisomerizations are depicted in Scheme 11.30. The oxidative coupling of a metal to an enyne yields a bicyclic metaUacyclopentene, which is a common intermediate. The reductive elimination and subsequent retro-[2+2] cycloaddition gave vinylcyclopentene derivatives, while the two patterns of P-elimination and subsequent reductive eUmination gave cychc 1,3- and 1,4-dienes, respectively. The existence of a carbene complex intermediate might explain the isomerization of the olefinic moiety. 

A ruthenium based catalytic system was developed by Trost and coworkers and used for the intermolecular Alder-ene reaction of unactivated alkynes and alkenes [30]. In initial attempts to develop an intramolecular version it was found that CpRu(COD)Cl catalyzed 1,6-enyne cycloisomerizations only if the olefins were monosubstituted. They recently discovered that if the cationic ruthenium catalyst CpRu(CH3CN)3+PF6 is used the reaction can tolerate 1,2-di- or tri-substituted alkenes and enables the cycloisomerization of 1,6- and 1,7-enynes [31]. The formation of metallacyclopentene and a /3-hydride elimination mechanism was proposed and the cycloisomerization product was formed in favor of the 1,4-diene. A... 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

Iridium-catalyzed intramolecular l,n-enyne metathesis has been studied as a unique tool for the synthesis of various types of cyclic compounds. Reactions of this type depend on both the structure of substrates and the nature of catalyst systems used (411). Recently, the cycloisomerization of various 1,6-enynes have been shown to be catalyzed by [Ir(cod)Cl]2/dppf (494). These reactions are highly stereoselective, and generate the (Z)-isomer preferentially over the ( )-isomer (Scheme 63). The proposed mechanism (Scheme 64) involves oxidative cyclization of the enyne at Ir(I) to give the trivalent iridacyclopentene. The intermediate undergoes (3-hydride elimination to give the irida-1,3-diene, which experiences steric repulsion between the metal fragment and the cis substituent on the... 

Two mechanistic pathways for Pd-catalyzed enyne cycloisomerizations have been proposed. While the palladacyclization followed by fi-hydride elimination is likely to be operative for Pd(ll) catalysts, Pd(0) complexes in combination with catalytic amounts of carboxylic acids enter a hydropalladation-cyclic carbopalladation-fi-hydride elimination cycle. This latter mechanism is particularly suited for the development of sequentially catalyzed processes. 

Proposed Mechanisms Different mechanistic pathways have been proposed for the metal-catalyzed cycloisomerization reactions. In the case of enynes, these are highlighted as (i) the metaUocyclopentene pathway, (ii) the tf-metal pathway, and (iii) the vinylmetal pathway (Scheme 7.10) [30]. 

SCHEME 7.25 (a) Zwitterions between metals and alkynes or alkenes and (b) proposed mechanism for the cycloisomerization of enynes... 

A number of cycloisomerization reactions of enynes to construct five-membered car-bocycles with a variety of transition metal catalysts have been reported thus far [24]. The mechanisms that have been proposed for the cycloisomerization of enynes include 1) hydrometallation of alkyne followed by carbometallation of the olefin ... 

Shortly after the discovery of enyne metathesis, Trost began developing cycloisomerization reactions of enynes using Pd(ll) and Pt(ll) metallacyclic catalysts (429-433), which are mechanistically divergent from the metal-carbene reactions. The first of these metal catalyzed cycloisomerization reactions of 1,6-enynes appeared in 1985 (434). The reaction mechanism is proposed to involve initial enyne n complexation of the metal catalyst, which in this case is a cyclometalated Pd(II) cyclopentadiene, followed by oxidative cyclometala-tion of the enyne to form a tetradentate, putative Pd(IV) intermediate [Scheme 42(a)]. Subsequent reductive elimination of the cyclometalated catalyst releases a cyclobutene that rings opens to the 1,3-diene product. Although this scheme represents the fundamental mechanism for enyne metathesis and is useful in the synthesis of complex 1,3-cyclic dienes [Scheme 42(fe)], variations in the reaction pathway due to selective n complexation or alternative cyclobutene reactivity (e.g., isomerization, p-hydride elimination, path 2, Scheme 40) leads to variability in the reaction products. Strong evidence for intermediacy of cyclobutene species derives from the stereospecificity of the reaction. Alkene... 

Electrophilic Au(I) complexes or their halide AuX analogoues typically cyclize enynes (I, Scheme 58) (475) by a 5-exo-dig pathway to give a variety of cycloisomerization and addition derivatives. The mechanism is proposed to involve formation of a cyclopropyl gold-carbene intermediate... 

Taking advantage of the rich chemistry of transition-metal-catalyzed cycloisomerization of 1,6-enynes, the electron-rich, conformationally blocked cyclohepta-1,3, 5-triene has been envisioned as a 6-% nucleophilic component [59]. Thus, cycloisomerization of l-(pent-4-ynyl)cyclohepta-l,3,5-trienes in the presence of catalytic amounts of platinum(II) chloride led to a formal intramolecular [64-2] cycloaddition in good to excellent yields [60]. These reactions are conducted at room temperature in toluene as the solvent. A heteroatom in the tether between the unsaturated subunits is tolerated, although in these cases other catalytic pathways were also observed. A mechanism involving cationic intermediates resulting from the nucleophilic attack of the triene on the metal-alkyne moiety has been proposed (Scheme 8.38). The occurrence of ionic intermediates was supported with... 

---