Aryl to alkyl palladium migration

Several different alkyl to aryl palladium migration processes have been also recently discovered using our standard palladium migration conditions (Scheme 28).24 Thus, both intramolecular Heck and intramolecular arylation... 

The first detailed study of alkyl to aryl palladium migrations, reported in 2004, involved homobenzylic to phenyl migration (Table 5) [58], The process was demonstrated using aryl iodides tethered to an olefin. An additional hap, either intramolecular arylation or intermolecular Heck olefination, was used to hap the migrated palladium. The reaction gives high yields of the desired polycyclic products. 

To date, palladium migration to vinylic positions remains unknown. Thus, palladium migration to sp2 carbons has been largely limited to aryl carbons. However, in addition to vinylic and aryl carbons, aldehydic and imidoyl carbons also possess sp2 hybridization and carry a C-H bond. This special type of sp2 C-H bond has also been subjected to palladium migration studies and preliminary success has been achieved. Currently, aryl to imidoyl [27] and aryl/alkyl to acyl [72] palladium migrations are known. Migrations from other types of carbons to imidoyl and acyl positions are... 

Subsequent studies on the reactivities of neutral and cationic alkyl- and aryl- palladium complexes revealed that the creation of a vacant site adjacent to the alkyl or aryl ligand causes marked enhancement in reactivity toward j8-hydrogen migration. The implications of these results on the fundamental processes of the transition metal alkyls and aryls with the mechanisms of Pd-catalyzed organic synthesis, such as arylation of olefins and carbonylation of aryl halides, have been discussed. 

Interestingly, when the aryl bromide homolog 23 was used, two regioisomeric isochroman products 24 and 25 were obtained in 1.7 1 ratio (Scheme 3.5). The desired product 24 is presumably formed via an alkylpalladium intermediate 24. On the other hand, an arylpalladium intermediate 25, generated by 1,4-palladium alkyl to aryl migration, would give product 25. This type of palladium migration has also been observed by Larock and coworkers [9] in the synthesis of fused polycycles. 

Among palladium 1,4-migrations, palladium can migrate from an alkyl to an aryl position in two different ways. One way is to migrate from a 1-naphthylmethyl position to a neighboring 8-naphthyl position in a naphthalene system. The other is to migrate from a homobenzylic position to an ortho phenyl position. Both processes have been observed. 

In addition to palladium, rhodium is also known to migrate from one carbon to another under suitable conditions. However, compared with palladium migration processes, rhodium migration is scarce. To date, only a few examples are reported, all involving 1,4-alkyl/vinylic to aryl migrations. 

The intermediacy of palladacycles in the reaction of bromobenzene with norbornene in the presence of Pd(PPh3)4 as catalyst and KOAc as a base in anisole as solvent was initially suggested by the isolation, among other products, of two compounds (Eq. 9), the former resulting from norbornene insertion into an alkylpalladium bond, the latter clearly deriving from palladium migration from the alkyl to the aryl site and double norbornene insertion. In both cases the termination step involved p,y-C-C bond cleavage followed by P-H elimination. The stereochemistry of the norbornane unit invariably was exo [19]. 

In Eq. 9 an intermediate palladacycle has been considered as responsible for the palladium migration from the alkyl to the aryl site. Further norbornene insertion resulted in the cleavage of a p,Y-C-C bond [19b]. 

Other Alkyl and Aryl Ethers.- Procedures for the selective removal of allyl ether in the presence of allyloxycarbonyl ester protecting groups, or vice versa, using palladium and iridium catalysts have been published in full (cf. Vol.19, p.l5). A reference to ester migration during 0 -allylatlon is covered in Chapter 7. 

Carbopalladation with double bond migration has been utilized to couple fragments. An example from the synthesis of potential anticancer agents is shown in Scheme Aryl iodide 60 couples with exo-alkene 59 to give 61 after Heck coupling and oxidation/arom-atization in modest yield. The reaction is unusual in that the carbopalladation intermediate contains a relatively unstable tertiary alkyl-palladium bond. 

A detailed reaction proving the nucleophilic attack was shown for platinum complexes [25]. The aUcoxide coordinated to platinum attacks phosphorus while the carbon atom coordinated to platinum migrates to phosphorus. Thermodynamically the result seems more favorable, but mechanistically this shuffle remains mysterious (see Figure 8). Coordination to platinum makes the phosphorus atom more susceptible to nucleophilic attack, and the harder atoms (P and O) and softer ones (C and Pt) recombine as one might expect. The same mechanism was proposed by Matsuda [22] for the decomposition of triphenylphoshine by palladium(II) acetate. In this study the aryl phosphines are used as a source for aryl groups that are converted into stilbenes via a Heck reaction. Even alkyl phosphines underwent P-C bond cleavage via palladium acetate. 

Addition of the nucleophile can take place by two sterically different pathways. In the first (path (a)), direct attack on the rj -allyl group occurs trans to palladium. This is by far the commoner route and is followed by stabilized carbanions such as CH(C02R)2, CH(C0R)2, PhCHCN and CgHg , and normally also with amines. Aryl and alkyl carbanions (e.g. R CuLi) or hydride however add initially to the metal centre and then migrate to the allyl group (path (b)). The stereochemistry of the product depends on which mechanism is followed (v.i.). 

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