Palladation reactions

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. 

The first example of the internal CH oxidative addition came from organic research with diazobenzene and PdClit2-. Cope and Siekman (1) discovered the palladation reaction of diazobenzene... 

However, while the kinetics according to eq. (9) have been included in the discussion [32] concluding that they would be valid for both the cis and trans oxy-palladation reactions (and accordingly a slight variant for the mechanism had been proposed), in none of the above papers have the kinetic findings according to eq. (13) [20] and the conclusions which have been drawn from them [12, 20] been considered. In the above experimental studies unsuitable model reactions have been used. 

The second ring is closed by an amido-palladation reaction. The nitrile in 151 is reduced to a primary amine and protected with a Boc group. Reaction with Pd(II) allows nucleophilic attack by the amide on the nearer end of the alkene and P-elimination again pushes the alkene round the ring 153, this time because there is no syn H atom in the intermediate 154 at the site of addition. Palladium is released as Pd(0) but this reaction needs Pd(II) so the quinone and MnOz are there to carry out the required oxidation. 

Myers AG, Tanaka D, Mannion MR (2002) Development of a decarboxylative palladation reaction and its use in a Heck-type olefination of arene carboxylates. J Am Chem Soc 124 11250-11251... 

The product of the palladation reaction exists as an active intermediate and cannot be isolated in general. However, the product of palladation was isolated as a stable compound in the reaction of cyclooctadiene palladium complex with carbanions such as malonate or alcoholate. Further reaction of the complex with base to give bicyclo (6,1,0) nonene and bicyclo (3,3,0) octane systems was reported by Takahashi and Tsuji 108>. The reactions are understood as intra-and intermolecular nucleophilic addition reactions. 

Coperet C, Negishi E (2002) Intramolecular Acylpalladation Intramolecular Acyl-palladation Reactions with Alkenes, Alkynes, and Related Unsaturated Compounds. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. WUey, New York, p 2519... 

Despite the plausibility of the mechanisms shown in Schemes 1 and 2, palladation of arenes and other C—H compounds can also be and may have to be interpreted differently. As in the mechanistic discussion of oxidative addition in Sect IL3.1 (Scheme 6), the crucial requirements in the activation of a o--bond by Pd may just be a combination of (i) binding of Pd via tt- or o--complexation and (ii) oxidative addition of a proximal cr-bond, specifically C— H bond here. Such mechanisms for benzyl and alkynyl C— H activation are shown in Scheme 3. The critical difference between Schemes 2 and 3 is that, in the latter, there is no element of j8-elimination. A wide variety of o-palladation reactions observed with heterosubstituted arenes, such as those shown in Scheme 4, are more readily explained by the mechanism shown in Scheme 3 than that in Scheme 2. 

Cyclic aryl palladium complexes (palladacycles) are readily available by palladation reactions starting from palladium(Il) salts and an arene having a directing group (Scheme 5-1). 

The orr/to-palladation strategy can also be used for the palladation reaction of more complex structures such as the paracyclophane amine below (Experimental Procedure below). ... 

After initial C-H palladation, reaction with the acetic anhydride gives an intermediate which yields the product, (117), after reductive elimination. Reaction in methanol or ethanol without added acetic anhydride gives the corresponding alkoxy-substituted products. 

Intramolecular oxy palladation and amido palladation reactions onto alkynes provide a convenient way for preparing concise functionalized heterocyclic structures. As nucleophiles carboxylic acids, amines, and amides have been used. Also, further functionalization of the double bond might be achieved via cross-coupling with in situ-formed organopal-... 

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