Suzuki-Miyaura reaction mechanism

In an ESI-MS monitoring study of the Suzuki-Miyaura reaction using a dichloro-bis(aminophosphine) palladium precatalyst, binuclear Pd complexes were detected after the reaction went to completion, indicating a catalyst sink or a resting state. Addition of starting reagents resumes the reaction, suggesting the active role of the binuclear complex as a reservoir of mononuclear active catalyst. Other interpretations propose the involvement of Pd nanoparticles in which binuclear Pd complexes act as a precursor or perhaps even the active catalyst, but the last possibility seems unlikely. A mechanism for this transformation was proposed based on the intercepted species (Scheme 10) [62]. 

Figure 2.11 Proposed mechanism for the Suzuki-Miyaura reaction.

Suryanarayana C. Mechanical alloying and miUing. Prog Mater Sci 2001 46 1-184. Schneider F, Szuppa T, Stolle A, Ondruschka B, Hopf H. Energetic assessment of the Suzuki-Miyaura reaction a curtate life cycle assessment as an easily understandable and applicable tool for reaction optimization. Green Chem 2009 11 1894-9. 

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]. 

THE SUZUKI-MIYAURA REACTION 19.6.1 General Considerations and Mechanism... 

The mechanism of the Suzuki-Miyaura reaction is presented in Scheme 19.43 [57a]. The hydroxides OH" plays three roles (i) formation of the reactive trans-ArPd(OH)L2 in the rds transmetallation with Ar B(OH)2, (ii) catalysis of the reductive elimiuation fi-om trows-ArPdAr Lj, and (ill) formation of unreactive Ar B(OH)3", leading to two kineticaUy antagonistic role in the rate of the transmetallation controlled by the concentration ratio [OH"]/[Ar B(OH)2], which must be smaller than 1 (Fig. 19.1a). 

SCHEME 19.43 Mechanism of the Suzuki-Miyaura reaction with wBu NOH as the base and the inhihiting role of countercations m. ... 

Therefore, water favors the Suzuki-Miyaura reaction involving carbonates by formation of OH". The mechanism is thus similar to that reported in Scheme 19.43. However, a small amount of OH" is generated, controlled by the amount of water. Consequently, compared to pure OH" at the same concentration as 003 ", the transmetallation is slower because of the low concentration of ArPd(OH)Lj. For the same reason, the reductive elimination is also slower, this is why an induction period is observed for the formation of the Pd" (Fig. 19.1b) [56b]. 

Chaiand Lautens [158] reported in 2009 an elegant tandem Pd-catalyzed Suzuki-Miyaura/direct arylation reaction (Scheme 1.48). A wide range of aryl, alkenyl, and alkyl boronic acids were screened. The reactions were performed using e/w-dibromovinyl substrates, which were catalyzed by SPhos, and gave JV-fused heterocydes. Water was found to accelerate the reaction. The mechanism is quite involved, and we will not go into it here, but first indications are that the Suzuki-Miyaura reaction occurring before the direct arylation. 

Coupling of (R)-IO and (R)-ll to (R)-12 is completed by the well-known Suzuki-Miyaura reaction where Pd(0) complex catalyzes the formation of the C-C bond (Sect. 6.3, Example 6.4). In the next step, the protecting group is eliminated and the C=C bond reduced by achiral Ir(I) complex to trans-(lR,4S)-14. It is important to note the wrong R configuration at the C(l) atom in this and the previous intermediate. Inversion of the configuration in (15,45)-15 is achieved by the Mitunobu reaction with diphenylphosphorylazide (dppa) as the source of nucleophilic azide ions in the presence of DBU. This reaction is the method of choice for the transformation of alcohols in many other functionalities, azides, esters, alkyl-aryl ethers, imides, sulfonamides, etc., and its mechanism is explained in considerable detail [21, 22]. 

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. 

With the role of the base established, another issue in the Suzuki-Miyaura reaction was to elucidate whether the mechanism for the transmetalation step involved either one or two phosphine ligands in the Pd catalytic species. On this issue, Maseras et al. reported a thorough computational study at DFT-B3LYP level of the full catalytic cycle for the coupling of vinyl bromide and vinylboronic acid H2C=CHB(0H)2 catalyzed by both [Pd(PH3)2] and [PdfPHj)] [71]. Moreover, alternative mechanisms for the transmetalation step depending on the cis or trans... 

As stated in the beginning of the section, the Stille reaction along with the Suzuki-Miyaura reaction are the most broadly studied C-C cross-coupling reactions [82]. For the transmetalation process involved in the Stille reaction two main mechanisms dubbed as cyclic mechanism and open mechanism have been proposed in order to account for the reported experimental evidences (Fig. 3.12). In particular, the cyclic mechanism was proposed to account for the evidences of Stille processes in which the products exhibit retention of configuration at the transmeta-lated carbon [83], whereas the open mechanism was proposed for processes in which inversion of configuration was observed [84]. 

In a detailed investigation of the mechanism and scope of palladium catalyzed amination of five-membered heterocycles, the 1-methyl-3-bromoindole 145 was aminated with secondary amines to the 3-aminoindoles 146. Similar results were obtained for l-methyl-2-bromoindole <03JOC2861>. Rhodium-catalyzed cyclopropanation reactions involving 1-methyl-3-diazooxindole and exocyclic alkenes provided novel dispirocyclic cyclopropanes <03SL1599>. New applications of palladium-mediated cross-coupling reactions have been utilized to prepare a variety of functionalized indoles. Suzuki-Miyaura coupling reactions of indole-3-boronates <03H(59)473> and indole-5-boronates <03H(60)865> were utilized to prepare inhibitors of lipid peroxidation and melatonin analogues, respectively. 

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