Suzuki-Miyaura reaction palladium-catalyzed

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

Historically, one of the most important limitations of the Suzuki-Miyaura reaction was the poor reactivity of organic chlorides, attributed to the strength of the C-Cl bond. Aryl chlorides are very attractive halides due to their low cost and wider diversity of available compounds. Prior to 1998, reports of effective palladium-catalyzed Suzuki reactions of aryl chlorides were limited to activated substrates, and generally employing very high temperatures. In that year. 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

Miyaura N, Suzuki A (1995) Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem Rev 95 2457-2483... 

The palladium-catalyzed Suzuki-Miyaura reaction of 3,5-dibromo-2-pyronc 100 with benzo[, ]furan-2-boronic acid 101 was applied to the synthesis of 3-(benzo[ ]furan-2-yl)-5-bromo-pyrone 102 in 50% yield (Equation 92) <2004SL2197>. 

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]. 

The palladium-catalyzed coupling of boronic acids (as well as other boron derivatives) with aryl and vinyl halides and psendohalides is known as the Suzuki or Suzuki-Miyaura reaction. Because boron is nontoxic, this reaction has been used in pharmaceutical syntheses. In addition, hydroboration or borate substitution allows for the synthesis of virtually any desired coupling partner. For these reasons, as well as the high yields and functional group compatibility, the Suzuki reaction is the first reaction to consider for carrying out a cross coupling. Representative substrates and catalysts are shown in Scheme 17. The various bases are used to generate four-coordinate boron ate complexes that are more reactive in transmetalation. 

Oh-e, T., Miyaura, N., and Suzuki, A. (1993). Palladium-catalyzed cross-coupling reaction of organoboron compounds with organic triflates. J Org Chem 58 2201-2208. 

Miyaura, N., Yanagi, T., Suzuki, A. The palladium-catalyzed cross-coupling reaction of phenylboronic acid with haloarenes in the presence of bases. Synth. Common. 1981,11, 513-519. 

A quite obvious solution to this problem is to replace both partners of the crosscoupling reaction with simple arenes by the cleavage of C-H bond during the coupling reaction. To assess this possibility, the catalytic cycle of the Suzuki-Miyaura reaction is depicted in Scheme 2. Palladium-catalyzed Suzuki-Miyaura reaction follows a similar catalytic cycle to those of many other cross-coupling... 

Scheme 15 Ligand-free palladium-catalyzed Suzuki-Miyaura reactions in the PASSflow reactor (first percentage refers to degree of transformation yields in parentheses refer to purified products)...

Miyaura, N. and Suzuki, N. 1995. Palladium-catalyzed cross<oupling reactions of organoboron comjxjimds. Chem. Rev. 95 2457-2483. 

A. Cassez, A. Ponchel, F. Hapiot, E. Monflier, Unexpected multifunctional effect of methylated cyclodextrins in a palladium charcoal-catalyzed Suzuki-Miyaura reaction, Org. Lett., 2006, 8, 4823 826 L. Strimbu, J. Liu, A. E. Kaifer, Cyclodextrin-capped palladium nanoparticles as catalysts for the Suzuki reaction, Langmuir, 2003, 19, 483 85. 

The Suzuki-Miyaura reaction has proven useful for synthetic chemists in the formation of aryl-aiyl bonds. Benefits include generally mild reaction conditions, compatibility with most functional groups, and the use of readily available boronic acids known for their stability. In the reaction shown below, Meldal and co-workers reported a palladium-catalyzed Suzuki cross-coupling reaction of a bromothiophene using a solid-phase synthesis protocol. ... 

Suzuki-Miyaura reactions are perhaps the most widely employed palladium catalyzed cross-couplings in the realm of thiazole medicinal chemistry. They typically take place only when the thiazole is an electrophile in the transformation. The nucleophilic thiazole boronic acid or ester, especially at the 2-position, is relatively unstable and therefore difficult to prepare. The electrophiles namely the 2-, 4-, or 5-substituted halothiazoles are often readily accessible in terms of their synthetic ease or commercial availability. A remarkable application has been described by Jang et al. in the discovery... 

Walker SD, Barder TE, Martinelli JR, Buchwald SL (2004) A Rationally Designed Universal Catalyst for Suzuki-Miyaura Coupling Processes. Angew Chem Int Ed 43 1871 Oh-e T, Miyaura N, Suzuki A (1990) Palladium-catalyzed Cross-coupling Reaction of Aryl or Vinylic Triflates with Organoboron Cmnpounds. Synlett 221... 

Selective palladium-catalyzed Suzuki—Miyaura reactions of polyhalo-genated heteroarenes 12ASC1181. 

Due to their widespread application in the Suzuki-Miyaura reaction, arylboronic acids are attractive aryl transfer precursors. However, in the zinc-promoted reaction, an excess of Et2Zn (up to 7equiv.) must be added in order for efficient transmetallation to occur. The application of a reactive aryl metal species necessitating only a catalytic amount of metal would thus be advantageous. In recent years, several rhodium-catalyzed enantioselective protocols have been described, as well as processes involving palladium and nickel. 

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]. 

For the Suzuki coupling reactions, see (a) Miyaura, N., Yanagi, T, and Suzuki, A., The palladium-catalyzed cross-coupling reaction of phenylboronic acid with haloarenes in the presence of bases, Synth. Comm., //, 513 (1981) (b) Suzuki, A., Organoborates in new synthetic reactions, Acc. Chem. Res., 15, 178-184 (1982) (c) Huber, J., and Scherf, U., A soluble poly(para-phenylene) composed of cyclophane units poly(2,5-(oxydecanoxy)-l,4-phenylene] Macromol. Rapid Commun., 15, 897 (1994). 

The palladium-catalyzed Suzuki-Miyaura reaction is a cross-coupling reaction between aryl halides and horon derivatives (Scheme 19.40) [54]. Snznki received the Nobel Prize in 2010 [54h]. Reactions are performed under mild conditions and many functional gronps are tolerated. Water is not a problem and may be even beneficial (vide infra). The first reported reactions hy Suzuki in 1979 insisted about the presence of a base, even if no proton is exchanged [54a, b]. Various bases have been used EtO, MeO", OH", CO ", and F" associated with countercations such as Na, K% Cs+, LP, nBu N+, Ag+, or TP [54, 55]. The role of the base has led to many mechanistic interpretations involving among them anionic arylborates as reagents [54g, 56]. 

Boronic acids and boronate esters serve a myriad of purposes, and the discovery of the Suzuki-Miyaura reaction facilitated the widespread interest and application of organoboron compounds. This palladium-catalyzed C-C bond forming reaction initiated renewed interest in the preparation of diversely functionalized boronic acids that would lead to valuable products. From this synthetic standpoint, Suzuki coupling reactions have been employed in the production of natural products and the preparation of materials of interest. " The search for interesting starting materials for the Suzuki reaction produced a series of methods to prepare boronic acids so these species could be exploited in further applications. These compounds... 

Palladium removal is a perennial problem when the Pd-catalyzed Suzuki—Miyaura reaction is used in the chemical industry. A group at GlaxoSmithKline have tried to address this issue [146]. In their drug discovery program leading to the key synthetic intermediate, ethyl 3-[4-(l,l-dimethylethyl)phenyl]-l//-indole-2-carboxylate, which involved the synthesis of a biaryl compound... 

The palladium-catalyzed Suzuki-Miyaura reaction is an extremely effective and versatile approach for selective carbon-carbon bond formatiOTi. Thus, the coupling between aiylboronic acids and aryl halides or triflates is frequently utilized for the preparation of biaryls [52,81,87,88,144—152] or fused heterocycUc systems [139-141, 153-157]. Other applications involve the synthesis of indazole-based thienyl... 

Scheme 49 Palladium-catalyzed Suzuki-Miyaura reactions with bromothiophenes [342]... 

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