Transmetallation palladacycles

Of the two mechanistic pathways, i.e., via palladacyclization or via hydropalladation-cyclic carbopalladation, the latter seems to be more suitable for the development of sequentially catalyzed processes. Considering cycloisomerizations via the hydropalladation-cyclic carbopalladation route the catalytic reaction can terminate by /1-hydride elimination giving rise to the formation of dienes and derivatives thereof (Scheme 79). Alternatively, the alkyl-Pd species formed in the cyclic carbopalladation can be susceptible to subsequent transmetallation with organometallic substrates. Then, a reductive elimination could conclude this second Pd-mediated step releasing the Pd(0) species for a new catalytic cycle. 

Only palladium- and platinum-containing heterocycles were described between 1995 and 2006. Mateo et a/, reported that iodoaryl stannane 70 reacts with Pd(PPh3)4 to afford palladacycle 71, as a result of an intramolecular Pd/Sn transmetallation of the intermediate oxidative addition arylpalladium(ll) complex (Equation 10) <1996CEJ1596>. 

Catellani found that the interaction of palladacycles such as 5 with aryl halides led to the incorporation of the aryl group in a manner analogous to alkyl halides [39], A similar mechanism could be proposed for the oxidative addition of aryl halides to palladacycles such as 5 to generate a palladium(TV) species, although to date there is no direct evidence for this pathway. An alternative mechanism has been put forward by Echavarren which involves transmetallation between two palladium... 

In the cross-coupling reaction, starting from the simple arene (with directing group), palladation by a Pd(II) salt would lead to the formation of the palladacyclic complex (Ar1Pd(II)L) (Scheme 3). After the transmetallation and reductive elimination processes, the biaryl product is obtained together with Pd(0). If the Pd(0) can be further oxidized to Pd(II) catalyst, a catalytic cycle will be formed. By accomplishing this, arenes (C-H) are used to replace the aryl halides (C-X). Similarly, arenes (C-H) can be used to replace the aryl metals (C-M). 

As in the other cases, oxidative addition and transmetallation are two main routes to palladacycles. Some representative examples follow. Oxidative addition of Pd into the C—Cl bond of MeSCH2Cl in the presence of 1 equiv of PPh3 gives a three-membered palladacycle.f In the presence of 2 equiv or more of PPh3 an acyclic species is formed (Scheme 33). The reaction of Cl2Pd(PPh3)2 with Li(CH2>4Li produces (CH2)4Pd(PPh3)2. >... 

Benzylic C—H activation can also occur readily to give five-membered palladacycles containing Pd—CspS bonds (Scheme 36). Five-membered palladacycles containing Pd—Csp3 bonds may also be prepared via transmetallation (Scheme 36). 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

The formation of phenanthridinones 98 from o-bromoamides 97 most Ukely involves a reaction between two metaUacycles (Scheme 11.33) [116, 117]. Accordingly, palladacycles 99 would react by a transmetaUation type-process to form 100 [116a], the elimination of which forms a seven-membered ring paUadacycle 101, followed by a reductive elimination to give phenanthridinones 98. Bimolecular transmetallation-type processes have also been proposed for the formation of other biaryls [69, 118]. 

Although the palladium(IV) species is often presumed to be an intermediate in this reaction, there is no experimental evidence for the oxidative addition of aryl halides to palladium(n) complexes. Echavarren and co-workers have foimd that this process may in fact proceed without the intermediacy of paUadium(IV) complexes. The authors conducted DFT calculations on model complexes to assess whether the reaction proceeds via oxidative addition of aryl halides to palladacycles to give palladium(rV) intermediates (path 1, Scheme 19.19), or by a transmetallation-type reaction of arene ligands between a palladacycle and a palladium(II) complex formed by the oxidative addition of an aryl halide to palladium(O) (path 2, Scheme 19.19). The results of this study suggest that the formation of C(sp )-C(sp ) bonds in this type of palladium-catalyzed reaction likely occurs without the intermediacy of palladium(IV) complexes. 

Mastrorilli et al. described a combined ESI HRMS and F NMR mechanistic study of this reaction with palladacycle complex 10 (Scheme 7.5) as the precatalyst [17], from which the authors postulated the formation of the true catalytic species in a first step. It is suggested that palladacycle 10 reacts with potassium trifiuorophenylborate 8a to give Pd(0) intermediate 117 (Entry 3, Table 7.3), which starts the catalytic cycle. This species undergoes oxidative addition of the aryldiazonium salt to give the cationic aryl-palladium(II) complexes 120, which contain azobenzene 11 as a ligand (Entry 4, Table 7.3). In this study, no intermediate was detected corresponding to transmetalation species. 

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