Cross-coupling reactions reaction mechanisms

Scheme 26 Two different mechanisms for cross-coupling reactions [9]...

The mechanism of a typical cross-coupling reaction catalyzed by Pd° or Ni° complexes can be represented by a standard catalytic cycle (Scheme 1, shown for Pd ancillary ligands not given, for simplicity). 

It proceeds by the standard mechanism for cross-coupling reactions oxidative addition of Pd(0) to the C-I bond, transmetallation to give the C-Pd(II)-C compound, and reductive elimination. 

Fig. 2 Plausible mechanism for the cross-coupling reaction of organobismuth compounds with organic halides and triflates...

Because of their frequent use, some late transition metal catalyzed carbon-carbon bond forming reactions evolved into name reactions. The most prominent examples are cross-coupling reactions, where distinction is usually made on the basis of the transmetalating agent used. The common mechanism of cross-coupling reactions and its name variants are discussed in Chapter 2.1. 

Figure 2.1. Cross-coupling reactions - mechanism and name reactions...

Fig. 14. Proposed mechanism for nickel-catalyzed cross-coupling reaction 66).

The formation of spirolactams 47-49 could be rationalized in terms of a sequence domino cyclization of a-allenols-cross coupling reactions. A palladium (Il)-catalyzed mechanism for the domino sequence leading to spiranic adducts 47-49 is proposed in Scheme 17. It could be presumed that the initially formed allenepalladium complex 50 undergoes an intramolecular attack by the hydroxyl group (oxypalladation), giving rise to the spirocyclic vinylic palladium species 51. 

It is assumed that the mechanism of the palladium-catalyzed cross-coupling reactions of iodonium salts involves the initial oxidative addition step, followed by ligand coupling at the iodine and then at the palladium centers analogously to the mechanism shown in Scheme 31 [63,66]. 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

Scheme8.3. Simplified mechanism of Pd-catalyzed cross-coupling reactions. R, R = aryl, vinyl, a I kynyl, allyl, benzyl, alkyl, acyl ...

It has been demonstrated by 1H, 13C, and 109Ag NMR that a 7r-alkyne-Ag complex and then an alkynyl silver are formed in situ from alkyne and silver salt under conditions related to those used for Ag-catalysed alkynylation or for Ag/Pd-catalysed sp-sp2 cross-coupling reactions.142 These observations have prompted a rationale of the mechanisms of these reactions. 

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]. 

Interestingly, the in situ generated ruthenium acetylide complex C5Me5(PPh3)Ru-C=CPh catalyzed the cross-coupling reaction of terminal and internal alkynes to yield functionalized enynes [87] (Eq. 65). A coordinatively unsaturated enynyl complex is postulated as an intermediate in this mechanism. 

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