Cross coupling mechanisms steps

Cross-coupling to form carbon heteroatom bonds occurs by oxidative addition of an organic halide, generation of an aryl- or vinylpalladium amido, alkoxo, tholato, phosphido, silyl, stannyl, germyl, or boryl complex, and reductive elimination (Scheme 2). The relative rates and thermodynamics of the individual steps and the precise structure of the intermediates depend on the substrate and catalyst. A full discussion of the mechanism for each type of substrate and each catalyst is beyond the scope of this review. However, a series of reviews and primary literature has begun to provide information on the overall catalytic process.18,19,22,23,77,186... 

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]. 

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 reductive elimination to form C-C and C-H bonds [45] is a crucial step in the cross-coupling processes, as well as many other transition metal-catalyzed reactions. Reductive elimination reactions comprise an early chapter in any organometallic text. Many examples of these reactions have been studied, and a great deal is known about the mechanisms of these processes. Similarly, the cleavage of C-H bonds by oxidative addition, including the C-H bond in methane, is now known [46]. Again, questions remain about how these reactions occur, but a variety of mechanistic studies have revealed key features of these reactions. Even some remarkably mild C-C cleavage reactions have now been observed with soluble transition metal complexes [47,48]. 

The Mechanism of the cross coupling reaction can be accommodated by an oxidative addition of 1-bromopropene to iron(l) followed by exchange with ethylmagnesium bromide and reductive elimination. Scheme 3 is intended to form a basis for discussion and further study of the catalytic mechanism. In order to maintain the stereospecificity, the oxidative addition of bromo-propene in step a should occur with retention. Similar stereochemistry has been observed in oxidative additions of platinum(O) and nickel(O) complexes.(32)(33) The metathesis of the iron(lll) intermediate in step b is ixp icted to be rapid in analogy with other alkylations.(34) The formation of a new carbon-carbon bond by the redilcTive elimination of a pair of carbon-centered ligands in step c has been demonstrated to occur... 

The palladium-catalyzed cross-coupling reaction of a vinyl or aryl stannane with an arylhalogenide or -triflate is known as a Stille reaction. The mechanism of this Stille reaction is outlined below The palladium precatalyst loses two ligands and forms the catalytic species 36. The catalytic cycle starts with the oxidative addition of the catalytic species 36 into the carbon-triflate bond of 23 forming complex 41, which, however, does not undergo the required transmetallation step with stannane 22. Therefore, the triflate ion is... 

In several papers [2,7,8,10,14,15] published by 1976 the following generic three-step mechanism for the Pd- or Ni-catalyzed cross-coupling was suggested, although few supporting mechanistic and structural data were provided (Scheme 1-6). 

The mechanism of the copper-mediated cross-coupling of iodoarenes and perfluoroalkyl iodides is supposed to be similar to that of related reactions involving the interaction of halogenoarenes with cuprous salts of organic nucleophilic anions (for example CuCN) [55] (Scheme 2.122). First a solvated perfluoroalkyl copper(I) complex is formed. This then coordinates to the iodoarene followed by exchange of ligands [56]. Several electron-transfer steps are probably involved in this process. 

The dotted arrows on the transmetallation step 243 show only what joins to what and are not intended as a serious mechanism. Indeed a better mechanism might involve addition of RO to the boron atom before transmetallation. This process can be used to couple aryl to aryl, vinyl to vinyl, and aryl to vinyl (either way round ). As boron compounds are much less toxic than tin compounds, the Suzuki coupling is often preferred industrially. Because each partner in the coupling reaction is marked in a different way - one with a boron atom and one with a halide - we can be sure that we shall get cross coupling reactions only. 

The mechanism of palladium/aryl halide amination is very closely related to that of cross coupling, with displacement of the halide on palladium (or copper or nickel) by an amine or A-anion instead of the trans-metallation step. In the case of Cu and Ni catalysis, it may proceed through M(0)-M(11) or M(l)-M(lll) cycles. 

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