Mechanism of the Suzuki Coupling Reaction

Shown in a simplified form in Figure 10.5, the mechanism of the Suzuki-Miyaura reaction involves initial reaction of the aromatic halide with the palladium catalyst to form an organopalladium intermediate, followed by reaction of that intermediate with the aromatic boronic acid. The resultant diorganopalladium complex then decomposes to the coupled biaryl product plus regenerated catalyst. 

The mechanism " of the Suzuki reaction is closely related to that of the Stille coupling reaction, and is also best described by a catalytic cycle ... 

The Suzuki Coupling (Section 24.5B) The Suzuki coupling reaction is a palladium-catalyzed reaction of an organoboron compound with an organic halide or triflate.The mechanism involves transmetallation, in which the substituent on the borane replaces a ligand on palladium, followed by reductive elimination to form the new C—C bond. 

Preparations of all these organic materials involve the constmction of new carbon-carbon bonds and have prompted the development of many catalytic cross-coupling reactions. One of the most reliable synthetic methods to form carbon-carbon bonds is transition metal-catalyzed cross-coupling between organo-metallic nucleophiles and electrophilic organic halides or pseudohalides, respectively (Scheme 2a). The mechanisms of common cross-coupling reactions such as the Suzuki, Negishi, or Stille catalysis can be described by a catalytic cycle, differ in detail, but all include three main steps in the order oxidative addition, transmetallation, and reductive elimination (Scheme 1). 

The catalytic alkane borylation whose mechanistic scheme is detailed in section 2.6 also works according to the same mechanism with benzene in the sense that it can be borylated by pinB-Bpin to form the phenylboronate ester in 82% yield using only 0.25 mol% of the same catalyst, [Cp Rh(T]" -C6Me6)]. This efficient reaction is extremely useful in view of the Suzuki coupling leading to aryl functionalization using such boron derivatives (see Chap. 19.3.8) ... 

The mechanism of the Suzuki reaction is believed to be similar to that of other well-established Pd-catalyzed cross-coupling reactions. " The active L Pd(0) catalyst is often generated in situ by coordination of added phosphine ligands to a stable source of Pd(0), such as Pd2(dba)3. In cases where Pd(II) complexes such as Pd(OAc)2 are used as precatalysts, these species are converted to the active LnPd(O) species under the reaction conditions. The catalytic cycle then commences with oxidative addition of the aryl halide (or related electrophile) to Pd(0), which generates Pd(II) intermediate 1 Reaction of the organoboron reagent with base leads to... 

SCHEME 3.12 Mechanism of the Suzuki cross coupling reaction. 

Scheme 9. Proposed mechanism for the Suzuki cross-coupling reaction of arene diazonium salts with potassium organotrifluoroborates based on ESl-MS investigation, m/z vaiues are given for cationic intermediates observed by ESl(+)-MS.

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. 

Palladium nanoparticles and other heterogeneous catalysts are often invoked as catalysts in cross-coupling processes [194, 195). Direct evidence in support of an oxidative-addition-promoted leaching mechanism has been recently obtained in the Suzuki-Miyaura reactions with nanoparticle catalysts, suggesting that true surface catalysis remains largely unknown with these heterogeneous catalysts [196]. 

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