Application of the Suzuki-Miyaura Reaction

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. 

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

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

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. 

Kotha S, Lahiri S, Kashinath D (2002) Recent applications of the Suzuki-Miyaura cross-coupling reaction in organic synthesis. Tetrahedron 58 9633-9695... 

Synthesis and Cytostatic Activity of Substituted 6-Phenylpurine Bases and Nucleosides Application of the Suzuki—Miyaura Cross-Coupling Reactions of 6-Chloropurine Derivatives with Phenylboronic Acids... 

S. Kotha, K. Lahiri, D. Kashinath, Recent Applications of the Suzuki-Miyaura Cross-Coupling Reaction in Organic Synthesis, Tetrahedron 2002, 58, 9633-9695. 

Development of catalytic systems with water as solvent is very important for industrial and environmentally friendly applications. Water is, in this respect, perhaps the ultimate solvent, because of its nontoxicity and ready availability. Lead-beater has published several papers reporting optimization of the Suzuki-Miyaura reaction for aqueous conditions [25, 26], Aryl bromides and iodides were coupled and isolated in good yields with an attractive ligandless procedure (Scheme 15.6). 

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. 

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. 

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... 

Kotha, S., Lahiti, K. and Kashinath, D. Recent applications of the Suzuki-Miyaura cross-coupling reaction in organic synthesis. Tetrahedron 58, 9633-9695 (2002). Miyaura, N., Yamada, K. and Suzuki, A. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Lett 2ti, 3437-3440 (1979). 

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)]. ... 

Polyurea-encapsulated palladium catalysts promote the phosphine-free Mizoroki-Heck reaction, which results in a high yield of cinnamates 46 (Scheme 86). The catalyst, which is easily recovered by filtration, is also applicable to the Suzuki-Miyaura and Stifle coupling reactions. 

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. 

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. 

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... 

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