Oxidative addition transmetallation

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

These are called cross-coupling reactions and usually involve three basic steps oxidative addition, transmetallation, and reductive elimination. In the transmetallation step an organic group is transferred from the organometallic reagent to palladium. 

The general catalytic cycle of the Stille reaction involves oxidative addition, transmetallation, and reductive elimination. 

A new C-C bond is formed between a nucleophilic C-Sn and an electrophilic C-Br. This Stille coupling proceeds through the standard oxidative addition, transmetallation, reductive elimination process characteristic of Pd-catalyzed cross-couplings. The mechanism was discussed in the text (Section 6.3.4). 

Such a catalytic cycle closely resembles that promoted by № 12( )2, quoted in Section III (equation 4158), where the same oxidative addition/transmetallation sequence is in action. 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

In the case of ortho-substituted aryl halides, which are less reactive towards Ni°(bpy)n the formation of the arylzinc intermediate likely involves the occurrence of a Ni°-bpy-Zn(II) complex, which by reduction leads directly to the oxidative addition-transmetallation process. According to this, the nickel catalyst is NiBr2bpy, without extra bipyridine. It is thus possible to prepare arylzinc halides from not easily reduced 2-chlorotoluene or 2-chloroanisole, but also, more importantly, from aryl bromides or chlorides bearing reactive functional groups (COR, C02R, CN). These compounds can then be added... 

Electrophilic haloarene function and nucleophilic areneboronic acid function undergo carbon-carbon coupling only in the presence of Pd(0) catalytic species. The general catalytic cycle for this aryl-aryl coupling, involving an oxidative addition-transmetallation-reductive elimination sequence, follows the mechanistic scheme shown in Figure 8.4 for aryl-alkyl coupling. 

The mechanisms and choice of catalyst, usually a palladium(O) phosphine complex, are the same as those of coupling reactions involving oxidative addition, transmetallation, and reductive elimination. Phosphines do not require additional base for the coupling with aromatic triflates and the reaction has no difficulty in distinguishing the two phosphines present. 

The transition metal-catalyzed coupling reaction that forms and cleaves the bonds of two organic molecules occurs by a sequence of oxidative addition-transmetalation (alkylation)-reductive elimination (Fig. 1) [1,7d, 32d-f,41]. 

Mechanism was first discussed of the reaction with benzylic and aryl haUdes in 1979 [8,9]. As shown in other protocols, the three-step catalytic cycle is widely accepted, that is, oxidative addition, transmetallation, and reductive elimination (Scheme 5). 

Mechanism The Pd- or Ni-catalyzed alkenyl-alkenyl and alkenyl-aryl coupling reactions may proceed according to Scheme 5.25, involving the oxidative addition, transmetallation and reductive elimination. 

A general catalytic cycle for the cross-coupling reaction of organometallics involves an oxidative addition-transmetallation-reductive elimination sequence, as depicted in Scheme... 

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. 

In his review of 1986, Stille proposed a mechanism based primarily on data obtained from the coupling of benzoyl chloride with tri-n-butyl(phenyl)tin. This proposal already clearly stated four main steps of the catalytic cycle oxidative addition, transmetalation, isomerization, and reductive elimination. 

The mechanisms and catalysts used in this Buchwald-Hartwig chemistry mirror those of coupling reactions involving oxidative addition, transmetallation, and reductive elirruna-tion. The first step, as usual, is oxidative insertion of Pd(0) into the aryl-halogen bond. The Pd(ll) complex now adds the amine so that both coupling partners find themselves bonded to the same palladium atom. The base eliminates H—1 from the complex and reductive elimination forms the Ar—N bond. 

The reaction of 17 (or 25) to give 19 (or 31) can not be explained by the oxidative addition-transmetallation-reductive elimination mechanism. In the reaction of 25, carbopalladation to form 26 and 27 is the first step. Desilylpalladation of 26 affords the expected ipso product 28. On the other hand, the intermediate 27 undergoes syn dehydropalladation to give 29, to which syn addition of H-PdX occurs to generate 30. Then anti desilylpalladation provides the cine product 31. This reaction is not completely fluoride-free, because the Bp4 anion is present. 

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