Suzuki arylating agent

Interestingly, when searching for new endogenous bioamine-interfering CNS agents, Bourguignon and co-workers found that the two orZ/zo-brominated aminopyridazines 4-bromo-6-phenylpyridazin-3-amine and A -benzyl-4-bromo-6-phenylpyridazin-3-amine (82) can be used as substrates in Suzuki arylation reactions without the need of any amino group protection [52]. 

Instead of aryl halides, arenediazonium salts are also excellent arylating agents in the Suzuki coupling, although more hindered arylboronic acids did not react The reaction is catalysed by several sources of ligand-free palladium such as Pd(OAc)2, Pd2(dba)3 and Pd/C at room temperature in dioxane without any added base [98]. Use of potassium aryl trifluoroborate salts also allowed the introduction of more sterically hindered aryl groups [99]. 

The Hiyama Coupling is the palladium-catalyzed C-C bond formation between aryl, alkenyl, or alkyl halides or pseudohalides and organosilanes. This reaction is comparable to the Suzuki Coupling and also requires an activating agent such as fluoride ion or a base. 

N-Arylation of phenylpyrrolylmethanone 199 to afford A -aryl derivative 200 was performed in Suzuki reaction conditions using phenylboronic acid, Cu(ii) acetate, and pyridine (Scheme 43) <2005JME5140>. The best yields were obtained in the presence of A -methylpyrrolidone (NMP) by microwave-assisted heating (60 W, 120 °C, 3 x 50 s). Reduction of methanone 200 with LiAlH4 gave methanols 201, which were then treated with GDI to afford imidazoles 202, potent anti-Candida agents. 

SAR studies were performed on compoimds containing the 9H-isothia-zolo[5,4-fc]quinoline-3,4-dione (ITQ) nucleus and it was found that some of them are potent antibacterial agents (see Scheme 101) [114,115]. They were prepared from compound 353, which was treated with cyclopropyl isothiocyanate in DMF and then with Mel. Compound 354 (94%) was obtained and treated with in NaH in DMF to give the isothiazolo[ 5,4-fo] quinoline compound 355 (93%). Its treatment with anhydrous NaSH gave the corresponding mercaptan (84%), which was directly cychsed without purification to 356 (85%) in the presence of hydroxylamine-O-sulfonic acid. Microwave-assisted Suzuki-Miyaura cross-coupling of the ITQ nucleus 356 with the desired aryl-boronic esters or acids afforded derivatives 357, typically, in 30-50% yield after HPLC purification (Scheme 87). 

Application of immobilized palladium catalyst under the action of MW, with phase-transfer agents, has also been reported to promote the Suzuki reactions of a range of aryl halides and triflates in solvents such as water and ethanol under MW conditions [120, 121]. Similar results were obtained when aryl halides were attached to a PEG matrix as para-substituted benzoates [122]. It was found that conventional thermal conditions induced up to 45% cleavage of the benzoates whereas this side reaction was suppressed when MW conditions were employed. 

In 2002, Rothenberg et al. reported on Suzuki reactions catalyzed by surfactant-stabilized colloids of Cu, Pd, Pt, or Ru or bimetallic combinations of these metals [29]. The colloids were prepared of metal salt solutions in DMF with tetraoctyl-ammonium formate, which served as a reducing agent as well as a stabilizer. Interestingly, mthenium and even copper coUoids were found to convert aryl iodides completely to the corresponding biphenyls, albeit more slowly than palladium colloids. 

Like Larock, Flynn and co-workers utilized various electrophilic cyclization reactions to produce desirable halo-benzothiophenes for use in cross-coupling reactions. The following benzothiophene synthesis involved a Suzuki cross-coupling reaction to form new aryl-aryl bonds at the C3 position. The product has been investigated in the search for potent tubulinbinding agents. ... 

Romagnoli et al. have reported a convergent synthesis of a class of microtubule targeting agents where they aj lied the Suzuki-Miyaura reaction to highly substituted 5-bromothiazoles. With various aryl boronic acid, highly substituted thiazole derivatives were prepared and evaluated for their anti-proliferative activity against a panel of human tumor cell lines. 

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