Suzuki-Miyaura reaction application

The Leznoff acetal linker 69 was used to anchor an aldehyde to the solid support and following a series of reactions, the aldehyde was released by acidic cleavage [78]. An application of this resin was demonstrated for a biaryl aldehyde library synthesis which incorporated a Suzuki-Miyaura reaction (Scheme 37) [79]. Cleavage was effected by a solution of 3 M HC1... 

The pincer-type palladacycle (120) (R = 1Pr), which is actually a derivative of a dialkylphos-phinous acid (themselves excellent ligands see Section 9.6.3.4.6) was shown to allow the crosscoupling of aryl chlorides with terminal acetylenes ((120), ZnCl2, Cs2C03, dioxane, 160 °C). However the high reaction temperature may be prohibitive for the actual application of this catalytic system, as acetylenes are known to be thermally sensitive.433 The same palladacycle (R = Ph) is effective in the Suzuki-Miyaura reaction with aryl bromides and activated aryl chlorides (K2C03, toluene, 130 °C). 

Application of the complexes 63 in the Mizoroki-Heck reaction did not reveal higher activity than the previously examined palladium(II) complexes. However, in the Suzuki-Miyaura reaction, a drastically increased activity was observed with complex 63. Catalysis starts without a measurable induction period at mild temperatures accompanied by an extraordinarily high turnover frequency (TOF) of 552 [mol product x mol Pd x h ] at the start of the reaction for the coupling of p-chlorotoluene and phenyl boronic acid [Eq. (48)]. ... 

In conclusion, the application of the Suzuki—Miyaura reaction of 6-chloropurine derivatives with substituted phenylboronic acids is a facile and effective approach for the synthesis of a series of specifically substituted 6-phenylpurine bases and nucleosides. In comparison with the previously known methods25-30 using other types of organometallic reagents or photochemistry, this method is more effective and selective, and therefore, further applications in the synthesis of 6 C-substituted purine derivatives may be expected. 

The development of catalytic systems using neat water as solvent is of high importance to industrial and environmentally friendly applications. In this respect, water is perhaps the ultimate solvent because of its lack of toxicity and ready availability. Leadbeater has published several papers where the Suzuki-Miyaura reaction has been optimized for aqueous conditions [9,120]. Aryl bromides and iodides were coupled and the corresponding products isolated in good yields with an attractive ligandless protocol. Some reactions gave increased yields with the addition of tetrabutylammonium bromide (TBAB) [121], Recently, an application for a scaled-up Suzuki-Miyaura synthesis in water using an automated batch stop-flow apparatus was also published (Scheme 46) [89]. 

Several publications have appeared dealing with Suzuki-Miyaura reactions producing heterocyclic products. These are interesting not only technically, because not all heterocyclic compounds are readily compatible with transition metal catalysis, but also because of the many applications of heterocyclic molecules in drug discovery. Indeed, several pharmaceutical companies have published high-speed or combinatorial synthesis-related reports describing the production of a variety of heterocyclic compounds [48],... 

Unprotected 4-heteroaryl phenylalanines have been prepared by microwave-assisted Suzuki-Miyaura reactions. Amino adds containing the biaryl motif have several interesting applications in medicinal chemistry and this method enabled their synthesis without protection of the amino acid. Optically pure boronic acids could be used without racemization (Scheme 15.16) [49]. 

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... 

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. 

Application of the Suzuki—Miyaura reaction in the synthesis of flavo-noids 13MOL4739. 

An interesting protocol by Bohn addresses these issues (Scheme 8.2) (8) by taking advantage of the use of boronic adds as the source of nucleophiles. Due to their widespread application in the Suzuki-Miyaura reaction, vast amounts of boronic adds are available commercially. TransmetaUation takes place from boron to zinc to form the active arylation reagent ArZnEt, which then selectively undergoes addition to the aldehyde using hgand 5. 

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. 

The most commonly employed aryl sources are arylboronic acids. Due to their widespread application in the Suzuki-Miyaura reaction, organoboronic acids have found wide acceptance, and currently more than 450 different arylboronic acids are available commercially [47]. These compounds unite several beneficial properties such as high air and moisture stability and great functional group... 

Dendritic catalysis have been used in various chemical reactions, including the Suzuki-Miyaura reaction, Mizoroki-Heck reaction, hydrogenation reaction, carbonylation and hydroformylation reactions, oxidation reaction, polymerization and oligomerization reactions, arylation reaction, alkylation reaction, and asymmetric synthesis [6]. Recently, dendritic catalysts have been reviewed by Astmc et al. [6], In another review article. Reek et al. reviewed the applications of dendrimers as support for recoverable catalysts and reagents [58]. The authors believed that catalytic performance in these systems depends on used dendritic architecture. 

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... 

Figure 13.1 Examples of the wide variety of applications of the Suzuki-Miyaura reaction.

As ean be seen from the above reports the Suzuki-Miyaura reaction has had and continues to have broad applicability across a wide manner of scien-tifle diseiplines, with a diverse series of applieations spanning pharma and materials ehemistry. There have been some fascinating developments of... 

In 2001, Fu s group [128] reported the application of Pd-triarylphosphane-ferrocene catalysts for the Suzuki-Miyaura reaction on aryl chloride substrates (Figure 1.40a). Activated aryl chlorides could be coupled at room temperature, while unactivated aryl chlorides, including sterically hindered and electron-rich substrates, at 70 °C. The triarylphosphane - which is air stable - was mixed with either Pd2(dba)j or Pd(OAc)2 with KjPO -HjO as base in toluene at room temperature, and very good yields were obtained. 

After a preliminary report [129], in 2006, Adjabeng etal. [130] reported the synthesis and application of novel phospa-adamantane ligands for the Pd-catalyzed Suzuki-Miyaura reaction. These compounds were originally reported by Epstein and Buckler in 1961 [132]. In this procedure, the phenyl derivative - l,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha-adamantane (Figure 1.40b) - was used in the arylation of aryl iodides, bromides, and activated chlorides with a variety of boronic acids at room temperature in a few hours with high yields. The ligand is comparable to P(fBu)j [126] with... 

Traditionally, arylboronic acids have been used in the Suzuki-Miyaura reaction, but considering the fact that arylboronic acids do not participate in the transmetallation process, different types of borate complexes have been devised. In 2006, Cammidge s group [139a] reported the application... 

Let us now consider some key synthetic applications of the Suzuki-Miyaura reaction in recent years. In the case of the synthesis of pharmaceuticals, this reaction has played a very prominent role. The excellent review by Magano and Dunetz [12k] describes many interesting examples of the application of this reaction in this industry. In our case, the following examples are particularly interesting and relevant. 

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