Palladation vinyl substitutions

It was demonstrated by Heck in the late 1960s that arylpaUadium salts, prepared by trans-metallation of organomercury compounds, constitute useful reactants in various vinylic substitution reactions.f t Independently, Moritani, Fujiwara, and colleagues conducted similar vinylic substitutions, but generated the organopalladium intermediates by direct electrophilic palladation of arenes.t ° In these reactions the palladium(II) salt employed is reduced to paUadium(O) (Scheme ). ... 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Abstract Palladium readily catalyzes the cross-coupling of functionally substituted aryl or vinylic halides and alkynes to afford a wide variety of heterocycles and carbocycles in one efficient step. Terminal alkynes presumably initially generate aryl (vinylic) alkynes, which under the reaction conditions are rapidly cyclized by the palladium or copper salts employed in the first step to produce the final product. Internal alkynes apparently react by carbo-palladation of the alkyne and subsequent intramolecular nucleophilic substitution of the palladium moiety to generate the observed products. A variety of other closely related processes have also been reported, including the simultaneous annulation of alkynes and car-... 

The Pd(II)-mediated reaction of benzene with alkenes affords styrene derivatives 164. The reaction can be vmderstood by palladation, insertion of olefin to give 163, and y3-H elimination [67,68]. In addition to benzene and naphthalene derivatives, electron-rich heteroaromatic compounds such as ferrocene, furan and thiophene react with alkenes to give vinyl heterocycles. The effect of substituents in this reaction is similar to that observed in the electrophilic aromatic substitution [69]. 

This approach has been used to efficiently assemble 3-vinyl indoles 13 with alkenes (Scheme 6.20) [28]. It was observed in this case that the nature of the nitrogen substituent influences the ability to trap the 3-palladated indole, with carbamates providing the highest yields. The elimination of HX from the palladium after P-hydride elimination creates a Pd(0) complex that is unable to mediate subsequent cyclizations. As such, co-oxidants, such as stoichiometric copper(II) salts, are used in this reaction to regenerate the palladium(II) catalyst. However, by modifying reaction conditions, Lu has found that the addition of excess LiBr can inhibit P-hydride elimination, and instead allow the formation of the reduced product (Scheme 6.21) [29]. This not only allows access to 3-alkyl substituted indoles, but also eliminates the need for stoichiometric oxidants. 

Kibayashi and coworkers [15] have introduced a sequential cyclic carbo-palladation-Stille vinylations of enyne compounds. Upon treating the enyne 1 and vinyl tributylstannane with catalytic amounts of system Pd2(dba)3-CHCl3/ AcOH (dba, dibenzylideneacetone), the allyl-substituted methylene cyclopentane 2 was formed in 53% yield (Scheme 12.1). The expected Alder-ene product 3 was not detected. This sequence was extended to heteroatom-tethered enynes 4 and vinyl tin compounds 5 to furnish heterocycles 6 in moderate to excellent yields. 

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