Benzyne carbopalladation

The palladium-catalyzed reaction of allyl chloride 11 with the benzyne precursor 104 to produces phenanthrene derivatives 131 is also known [83]. A plausible mechanism for this intermolecular benzyne-benzyne-alkene insertion reaction is shown in Scheme 38. Initially n-allyl palladium chloride la is formed from Pd(0) and 11. Benzyne 106, which is generated from the reaction of CsF and 104, inserted into la to afford the aryl palladium intermediate 132. A second benzyne insertion into 132 produce 133 and subsequent carbopalladation to the alkene afford the cyclized intermediate 134. f>- Iydride elimination from 134 followed by isomerization gave 9-methylphenanthrene 131. 

This unexpected result is plausibly due to the rate of generation of benzyne depending on the solvent used [69]. As in Scheme 30, the key intermediate is presumed to be the result of an oxidative addition-carbopalladation sequence,... 

Subsequent C-H activation generates the five-membered paUadacycle 65, which undergoes intermolecular carbopalladation with aryne 66 to give seven-membered paUadacycle 67. FinaUy, reductive ehmination furnishes the product 62 and regenerates the palladium catalyst. Overall, three C-C bonds are constructed in this reaction sequence. In an earher report, Tanaka and coworkers [23] had observed similar domino reactions with bromoenynes to synthesize benzoisoindoles in the absence of external benzyne acceptors. 

The above reaction conditions are only suitable for electron-deficient alkynes. When electron-rich alkynes are used, the corresponding phenanthrenes are obtained in only low yields (up to 34%). At about the same time, the Yamamoto group independently developed a palladium-catalyzed cotrimerization of benzyne with alkynes [118] where the yields of phenanthrene products generated from electron-rich alkynes could be dramatically increased to >59% in the presence of a Pd(OAc)2/P(o-tolyl)3 catalyst system. This process was, however, later shown to proceed through a Pd(0) insertion-carbopalladation process, rather than a free benzyne process [119]. 

Polycyclic Arenes. Trimethylsilylphenyl triflates have found widespread use as benzyne precursors in the preparation of polycyclic arenes. Triphenylenes are made via paUadium-catalyzed [2 + 2 + 2] cyclotrimerization of arynes, by paUadium-catalyzed annulation of the aryne and 2-halobiaryls, or via carbopalladation/carbocycUzation of arynes with substituted iodobenzenes (eq 2). All three approaches furnish substituted triphenylenes in high reported yields. Substituted phenanthrenes or naphthalenes are similarly prepared using 2-(trimethylsilyl) phenyl triflate as an aryne precursor. Treatment of the reagent with fluoride, a palladium catalyst, and a deactivated alkene, allyl halide, or internal aIk5Tie provides 9-substituted or 9,... 

Carbopalladation of Arynes by n-Allylpalladium and Related Complexes. Pioneering work from Yamamoto established that ji-allylpalladium species are particularly effective for the carbopalladation of arynes leading to an arylpalladium intermediate 109, which can be employed in three-component couplings with a second aryne to give phenanthrenes such as 110, or with alkynes to produce naphthalenes such as 111. In the first case, 109 evolves through insertion of another benzyne (1) molecule (carbopalladation of 1 by an arylpalladium) and further carbopalladation of the pendant alkene to afford a tricyclic species that undergoes p-hydride elimination (Scheme 12.55) [96],... 

Greaney et al. introduced the Heck reaction to the benzyne three-component coupling to prepare 1,2-functional-ized arenes 28 and 29. Alternatives to allyl chlorides as the initial carbopalladation electrophile were presented, that is, methyl bromoacetate and benzyl bromides, thus avoiding the formation of benzyne/benzyne/allyl by-products and therefore improving the efficiency of the reaction [39], When using aryl iodides as the electrophilic partners, highly functionalized biaryl compounds 30 are obtained (Scheme 3.20) [40]. 

J. L. Henderson, A. S. Edwards, M. F. Greaney, J. Am. Chem. Soc. 2006, 128, 7426-7427. Three-component coupling of benzyne domino intermolecular carbopalladation. 

Mono- or di-arylaied products may be formed by a-arylation of -dicarbonyl compounds, such as malonamide esters, with arynes generated by reaction of fluoride with ortho-silylaryltriflates. A similar method of benzyne generation has been used in the a-arylation of -ketoamides in a procedure which may be modified to yield asymmettic products. The reaction of 2-haloacetanilides with arynes in the presence of a palladium catalyst may produceiV-acylcarbazoles such as (26). Possible pathways are initial formation of a palladacycle with aryne followed by oxidative addition of the haloacetanilide, or direct insertion of the palladium into the carbon-halogen bond of the acetanilide followed by carbopalladation of the aryne. ... 

---