Vinylallene intermediate

The mechanism of reaction involves a process consisting of an intramolecular ene reaction between two alkynes to give a vinylallene intermediate, which then undergoes an intramolecular Diels—Alder reaction with the double bond to give the fused tetracyclic product. 

The synthetic utility of the remarkably facile and efficient [2,3]-sigmatropic rearrangement of propargylic sulfenates has been further demonstrated in a variety of preparations and interesting reactions of allenyl sulfoxides , including the preparation of vinylallenes " which are useful intermediates in organic synthesis in general and natural polyenes, such as Vitamins A and D, in particular Two typical examples, taken... 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

In other examples, also involving propargyl carbonates, the parent derivative 86 was first coupled with 87 - obtained by reaction of 5-octyne with the titanium diiso-propoxide - propene complex at -50 °C, providing the titanated vinylallene 88, which on hydrolysis furnished the vinylallenes 89 in good yield [29]. Carbonate 90 in the presence of a Pd° catalyst readily decarboxylated and yielded the allenylpalladium intermediate 91, which could be coupled with various vinyl derivatives to afford the vinylallenes 92. Since X represents a functional group (ester, acetyl), functionalized vinylallenes are available by this route [30]. 

Beginning with vinylallene (2) as a prototype, four double bond extended hydrocarbons can be constructed 3, 4, 22 and 23. They have all been prepared and characterized or generated as reactive intermediates. 

The oxidative cyclization of vinylallenes need not be directed by a pendant hydroxyl group in order to succeed. The higher reactivity of the allene compared with the exocyclic methylene group in 73 (Eq. 13.23) with monoperphthalic acid leads primarily to the allene oxide which rearranges to cydopentenone 74 [27]. Inevitably some epoxidation of the alkene also takes place during the reaction. When m-CPBA is used as the oxidant, another side reaction is associated with m-chlorobenzoic add-mediated decomposition of the intermediate epoxide. It is possible to overcome this problem by performing the epoxidation in dichloromethane in a two-phase system with aqueous bicarbonate so as to buffer the add [28]. 

Mercuric acetate and thallic acetate have also been used for the oxidative cydiza-tion of vinylallenes (Eq. 13.24) [29]. Exposure of vinylallene 75 to stoichiometric mercuric acetate in acetic acid led to cydopentenone 76 in 75% yield. With thallium acetate as the oxidant, the yield of 76 was 60%. The presumed mechanism of the oxidative cyclization involves a Nazarov cyclization of acetoxymercury intermediate 77. 

In a different approach, Franck-Neumann et al. [24] utilized the manganese complex 14 (formed by deracemization) to obtain the enantiomerically pure target molecule 12 via Horner-Wadsworth-Emmons olefination and oxidative decomplexation of the intermediate vinylallene complex 15 (Scheme 18.6). 

The use of vinylallenes as the diene component in Diels-Alder reactions is very common, thus resulting in their ubiquitous use in natural product synthesis. A vinylal-lene has even been proposed by Schreiber and Kiessling [10] as a biogenetic intermediate in the synthesis of the skeleton of esperamicin A (32 —> 33). Their synthetic approach to esperamicin A (34) was modeled after this biogenetic proposal in which a Type II intramolecular Diels-Alder cycloaddition was used to gain access to the highly unsaturated bicyclic core of 34 (Scheme 19.8) [10]. 

In addition to the [3-1-2] and [2-I-2-I-1] carbocycHzations that facilitate the formation of five-membered rings, the [4-t-l] carbocycHzation also has merit. Several transition metals have been engaged in this transformation [37], wherein it was found that vinylallene 63 a reacts with 1 equiv of WiUdnson catalyst to afford the planar (T2-bonded (vinylallene)rhodium complex 64a upon simple ligand displacement (Scheme 11.16). The stmcture of 64a was confirmed unambiguously by X-ray crystallography, and represents the first structural characterization of a metallacycle intermediate [38 a]. 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

Asymmetric epoxidation has been performed with optically active peracid. " and racemic oxiranes have been resolved on a glc column containing an optically active complex. The epoxidation of allenes has been examined, as have the reactive intermediates formed in the epoxidation of simpler allenes. Such intermediates have been isolated from sterically hindered allenes. PNPBA epoxidation of a series of vinylallenes results in a-allenoxiranes and, as the main products, conjugated cyclopentenones. ... 

A similar electrophilic activation of the vinylallene to 2-cyclopentenone cyclization is possible using either mercury(II) acetate or thallium acetate. Solvometallation of allenes is a well studied pro-cess following expected Markovnikov attack at the central carbon by the metal salt. The yield of cyclopentenones was generally higher with acetoxymercuration (49-79%) compared to acetoxythallation (25-68%). Compounds of similar substitution pattern as were investigated with epoxidation (Scheme 31) were prepared. Mechanistically the reaction is remarkable for the facility of solvodemercuration (Scheme 33). Intermediates such as (69) or (70) lose elemental mercury spontaneously in the acetic acid medium to give the 2-cyclopentenones. 

MO calculations show that the diradical stepwise pathways are preferred over the concerted paths in the Diels-Alder cycloaddition of strained allenes, such as cyclohexa-1,2-diene, with cyclobuta-l,3-diene. An ab initio study of the regio- and stereo-selectivity of the Diels-Alder reaction of vinylallenes and methyl-substituted vinylallenes with acrolein showed the reactions to be asynchronous. Allenamides undergo inverse-electron-demand 4 - - 2-cycloaddition with alkyl vinyl ketones to yield pyranyl ketones. The cycloaddition of (silyloxyvinyl)cyclohexene (147) with the allenecarboxylate (148) produced the exo-cycloadduct (149), which is a key intermediate in the total synthesis of the phosphatase inhibitor dysidiolide (Scheme 57). ... 

Weak base such as cesium carbonate has been utilized in this reaction to generate diazo compounds in situ from tosylhydrazones through the Bamford-Stevens reaction. The reaction is initiated by palladium-promoted decarboxylation of propargylic carbonate to form propargylpalladium complex A, which then tautomerizes to afford allenylpalladium intermediate B. Subsequently, the common carbene formation-migratory insertion-p-hydride elimination occurs to afford various vinylallenes (Fig. 30). 

The oxidation of cyano-Gilman cuprates has enabled the synthesis of new cyclophanes. Moreover, while BuhCuLi-LiCN has been reported to effect vinylallene formation by the 1,5-substitution of enyne acetates, it has been revealed that the application of Bu"3P to the reaction system considerably enhances the enantioselectivity of the synthesis. " Recent kinetic isotope studies into the chlorotrimethylsilane-mediated addition of lithiocuprates to cyclo-hexenone have suggested that reaction proceeds via an intermediate rr-com-plex. ... 

The mechanism of this reaction is considered in Scheme 2.87 [3]. The metal-containing cyclopentene 2.260, formed from the initial vinylallenes 2.259 and rhodium catalyst, is probable the reaction intermediate. Next is the introduction monoyne 2.261 to the metallocycle 2.260 to... 

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