Palladium complexes nucleophile transmetallation

Transition-metal-catalysed reactions of glycals with carbon nucleophiles provide an important route to C-glycosides.24 These reactions may proceed by two different pathways depending on the oxidation state of the transition metal used and the nature of the carbon nucleophile (Scheme 3.5c). For example,25 transmetallation of Pd(OAc)2 with pyrimi-dinyl mercuric acetate results in the formation of a pyrimidinyl palladium complex, which adds to the double bond of glycal derivatives. The resulting intermediate can undergo different transformations depending on the reaction conditions. 

Oxidative addition of certain stannanes to Pd(0) complejKS is also possible. Thus, aUcynylstannanes have been shown to react with Pd(0) complexes [207, 208). In addition, the Pd(0)-catalyzed reaction of allylstannanes with alkynes has been found to afford aUylstannylation products 31 (Scheme 1.23) [209]. A likely mechanism involves oxidative addition of the allylstannanes to Pd(0) to give (ri -allyl) palladium complexes 32 (L = alkyne) (Scheme 1.23). In this transformation, the usually nucleophilic allylstannanes behave as electrophiles. Complexes of type 32 are probably formed by transmetallation of (T) -aUyl)palladium complexes with hexamethylditin [210]. An oxidative addition to form complexes 32 has been proposed in the Pd(0)-catalyzed carboxylation of allylstannanes with COj [211]. Although compleres 32 have not been isolated as stable species, work on the intramolecular reachon of allylstannanes with alkynes and theorehcal calculations give support to the formation of these complexes by the oxidahve addition of allylstarmanes to Pd(0) [212]. 

Allylic complexes of palladium can be used as a source of the allyl moiety to synthesize other metal -allylic complexes. Redox transmetallation to a Pt(0) complex leads to a platinum 77 -allyl derivative (Equation (44)). The reaction is easier when a cationic palladium allyl is used, and can be viewed as a nucleophilic attack of the Pt(0) complex to the allylic fragment. The transmetallation takes place with inversion of configuration of the allyl group. The same reaction occurs with Pd(0) complexes, a redox exchange with inversion of configuration of the allylic fragment. However, when a neutral palladium(ll) 77 -allyl complex is employed, the reaction leads to dimeric palladium(l) derivatives, as discussed before (Equation (41)). 

Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl boronic ester provide substituted cyclopentenes in high yields and diastereose-lectivities (Scheme 6.24). These reactions are hypothesized to commence by the conjugate addition of a nucleophilic propargyl-palladium complex. Transmetalation of allenylboronic acid pinacol ester with a Pd(II) catalyst proceeds via an SE2 mechanism to provide the propargyl-palladium complex, which on conjugate attack on the electrophile furnishes an allene intermediate. Finally, endo carbopalladation of the pendant allene and protodepalladation generates the cyclopentene [28]. 

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

The mechanism involves oxidative addition of the halide or triflate to the initial palladiumfO phosphine complex to form a palladium(II) species. The key slow step is a transmetallation, so calk because the nucleophile (R1) is transferred from the metal in the organometallic reagent to the palla dium and the counterion (X = halide or triflate) moves in the opposite direction. The new palladi um(II) complex with two organic ligands undergoes reductive elimination to give the couple product and the palladium(O) catalyst ready for another cycle. 

The mechanism is very similar to that of the Stille coupling. Oxidative addition of the vinylic or aromatic halide to the palladium(O) complex generates a palladium(II) intermediate. This then undergoes a transmetallation with the alkenyl boronate, from which the product is expelled by reductive elimination, regenerating the palladium(O) catalyst. The important difference is the transmetallation step, which explains the need for an additional base, usually sodium or potassium ethoxide or hydroxide, in the Suzuki coupling. The base accelerates the transmetallation step leading to the borate directly presumably via a more nucleophilic ate complex,... 

Many nncleophiles add to one of the double bonds of chelating palladium(diene) complexes to give a chelating Pd alkyl(alkene) derivative, as exemphfied by the reaction of PdCl2(l,5-cod) with methoxide (equation 41). In most cases, the direction of attack is exo. If the nucleophile is in a form that can undergo transmetalation with the Pd l bond, such as Ph2Hg, the nucleophihc group can be delivered endo. In this case, prior formation of a Pd nucleophile bond accounts for the direction of attack (equation 42). 

The chemistry of palladium is dominated by two stable oxidation states the zero-valent state [Pd(0), d ] and the +2 state [(Pd(II), d ]. Each oxidation state has its own characteristic reaction pattern. Thus, Pd(0) complexes are electron-rich nucleophilic species, and are prone to oxidation, ligand dissociation, insertion, and oxidative-coupling reactions. Pd(II) complexes are electrophilic and undergo ligand association and reductive-coupling reactions. A large amount of literature deals with these reactions. However, a few fundamental principles, such as oxidative addition, transmetalation, and reductive elimination, provide a basis for applying the chemistry of palladium in research. 

The catalytic cycle for the Suzuki cross-coupling reaction involves an oxidative addition (to form RPd(II)X)-transmetalation-reductive elimination sequence. The transmeta-lation between the RPd(lI)X intermediate and the organoboron reagent does not occur readily until a base, such as sodium or potassium carbonate, hydroxide or alkoxide, is present in the reaction mixture. The role of the base can be rationalized by its coordination with the boron to form the corresponding ate-complex A, thereby enhancing the nucleophilicity of the organic group, which facilitates its transfer to palladium. Also, the base R O may activate the palladium by formation of R-Pd-OR from R-Pd-X. 

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