Transmetallation and Reductive Elimination

Formation of ketones. Ketones can be prepared by the carbonylation of halides and pseudo-halides in the presence of various organometallic compounds of Zn, B, Al, Sn, Si, and Hg, and other carbon nucleophiles, which attack acylpalladium intermediates (transmetallation and reductive elimination). 

The carbonylation of aryl iodides in the presence of alkyl iodides and Zn Cu couple affords aryl alkyl ketones via the formation of alkylzinc species from alkyl iodides followed by transmetallation and reductive elimination[380]. The Pd-catalyzed carbonylation of the diaryliodonium salts 516 under mild conditions in the presence of Zn affords ketones 517 via phenylzinc. The a-diketone 518 is formed as a byproduct[381],... 

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. 

Oxidative addition of Pd(0) to a c/s-dihaloethylene gives an intermediate that can undergo 3-halide elimination. The C-Br or C-I bond is more prone to undergo (3-elimination than the much stronger C-Cl bond. The transmetallation and reductive elimination steps of the Sonogashira coupling have more time to occur when a C-Cl bond is (3 to Pd than when a C-Br or C-I bond is (3 to Pd. 

An acyl-palladium complex might undergo a series of follow up reactions. Subsequent transmetalation and reductive elimination lead to the formation of a carbonyl compound. This process is also coined carbonylative coupling, referring to the cross-coupling reaction, which would take place in the absence of carbon monoxide under similar conditions (for more details see Chapter 2.4.). 

The coupling of the same boronic acid was also achieved with 4-chlorobenzoyl chloride (6.5.), Running the reaction under anhydrous conditions the desired 2-(4 chlorobenzoyl)thiophene was obtained in good yield.7 The opening step in this process is the selective oxidative addition of the palladium into the carbonyl-chlorine bond giving an acylpalladium complex, which on subsequent transmetalation and reductive elimination gives the observed product. 

The palladium-catalyzed reaction of aryl- and vinyl-tin reagents with stereochemically defined allyl chlorides proceeds with overall retention of configuration, indicating that the second step, entailing interaction of the iT-allylpalladium complex and the organotin, proceeds by transmetallation and reductive elimination (attack at Pd, retention) (equations 166 and 167).142145 Comparable results were obtained with cyclic vinyl epoxides and aryltins.143... 

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... 

Under certain conditions, aroyl chlorides are converted to arylsilanes by the reaction with disilanes. The oxidative addition of aroyl chloride and decarbonylation are followed by transmetallation and reductive elimination to give aryl silanes. Neat trimellitic anhydride acid chloride (377) reacts with dichlorotetramethyldisilane (376) at 145 °C to generate 378, which affords 4-chlorodimethylsilylphthalic anhydride (379) by reductive elimination. Finally it was converted to 380 and used for polyimide formation [185], Biphenyltetracarboxylic anhydride 381 is obtained at a higher... 

Alkylpalladium complexes generated by oxidative addition of Pd(0) to alkyl halides with a /3 hydrogen can undergo /3-elimination to yield an alkene and a Pd-hydrido complex (as in the Heck reaction Scheme8.7). Nevertheless, this process is relatively slow compared with transmetalations and reductive eliminations, and simple alkyl halides or tosylates with /3 hydrogen can be cross-coupled with carbon nucleophiles under optimized conditions if the nucleophile is sufficiently reactive [9, 73-75] (Scheme8.6). 

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]. 

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. 

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. 

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 cross-coupling reaction of the sp carbon with the sp carbon entails oxidative addition, Cu(I) catalyzed transmetalation, and reductive elimination. 

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). 

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