Suzuki elimination reaction

Bulky ligands as above have also proved to be effective in other palladium-catalyzed reactions of aryl halides, e.g., amination [16-19], Suzuki-Miyaura reaction [20-22], Mizoroki-Heck reaction [23, 24], Migita-Kosugi-Stille reaction [25], and aryloxylation and alkoxylation [26-28] as well as the reaction with various carbon nucleophiles as described below. The ligands are considered to enhance both the initial oxidative addition of aryl halides and the reductive elimination of products [29, 30]. The effectiveness of the commercially available simple ligand, P(f-Bu)3, was first described for the amination by Nishiyama et al. [16]. 

However, the true greenness of this reaction remained far from being ideal, as the necessity to prepare initially the arylboronic acids (or their derivatives) as nucleophilic starting material and to recycle (or to eliminate) the associated waste thereafter violate several of the TPGC. Hence this not only contradicts the concept of atom economy [35], but also increased Sheldon s environmental impact factor E (E = kgwaste/kgproduct) [36]. As a consequence, this resulted in a decrease in the value of the reaction mass efficiency (RME) forthe Suzuki-Miyaura reaction. The value RME = 1 characterizes an absolutely green reaction, but all reactions with RME >0.618,... 

The three basic steps in the palladium-catalysed Suzuki-Miyaura reaction involve oxidative addition, transmetalation, and reductive elimination. A systematic study of the transmetalation step has found that the major process involves the reaction of a palladium hydroxo complex with boronic acid, path B in Scheme 3, rather than the reaction of a palladium halide complex with trihydroxyborate, path A. A kinetic study using electrochemical techniques of Suzuki—Miyaura reactions in DMF has also emphasized the important function of hydroxide ions. These ions favour reaction by forming the reactive palladium hydroxo complex and also by promoting reductive elimination. However, their role is a compromise as they disfavour reaction by forming of unreactive anionic trihydroxyborate. A method for coupling arylboronic acids with aryl sulfonates or halides has been developed using a nickel-naphthyl complex as a pre-catalyst. It works at room temperature in toluene solvent in the presence of water and potassium carbonate. ... 

A detailed study of the transmetaUation in the Suzuki-Miyaura reaction by the group of Amatore and Jutand shows that hydroxide [261] and fluoride anions [262] form the key trans-[ArPdX(L)2] complexes that react with the boronic acid in a rate-determining transmetaUation. In addition, the anions promote the reductive elimination. Conversely, the anions disfavor the reaction by formation of nonreactive anionic [Ar B(OH)3 X ] (7t=l-3). Countercations M" " (Na" ", K" ", and Cs+) of anionic bases in the palladium-catalyzed Suzuki-Miyaura reactions decelerate the transmetaUation step in the following decreasing reactivity order nBu4NOH > KOH > CsOH > NaOH this is due to the complexation of the hydroxy ligand in [ArPd(OH)(PPh3)2] by M+[263]. 

An ESI-MS/MS study by CID (collision-induced dissociation) of the Suzuki-Miyaura reaction with palladium-diene catalysts showed that in this system, the reductive elimination step determines the rate of the whole process [361],... 

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. 

Several unusual silametacyclophanes, macrocyclic cage compounds, have been prepared by multiple Pd(0)-catalyzed Suzuki coupling reactions of 9-BBN adducts of allylsilane and bromobenzene. For example, reaction of 9-BBN adduct of methyltriallylsilane and 1,3,5-tribromobenzene leads to 4-methyl-4-sila[3 - ][7] metacyclophane, 4-(2-propenyl)-4-methyl-4-sila[7]metacyclophane, which results from an intramolecular coupling of two legs of the silane and -elimination of the third leg and 4-(3-phenylpropyl)-4-methyl-4-sila[7]metacyclophane (Eq. 

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]. 

Scheme 2.14 General catalytic cycle for the Suzuki coupling reaction, depicting a oxidative addition, b ligand exchange, c transmetallation and d reductive elimination steps...

Isoxazoles have also been obtained through an elimination reaction (Scheme 11.40). Cycloaddition of nitrile oxide to resin-bound vinyl ether gave resin-bound 2-isoxazoUne, which aromatized to isoxazole after the elimination of the polymer support. A regioselective reaction gave isoxazoles in high purity and with 36—83% yield. Enhanced diversity was obtained with the Suzuki coupling reactions to the R group prior to the cycloadditions. 

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]. 

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