Suzuki microwave promoted

The first example of microwave-promoted solid-phase methodology in heterocyclic chemistry was the arylation of thiophene and indole via Suzuki couplings on TentaGel S RAM resin, as demonstrated by Hallberg and coworkers in 1996, before temperature- and pressure-controlled microwave instruments were even available [189]. Three years later Schotten and coworkers presented analogous but aqueous Suzuki couplings of 5-bromo-thiophene anchored to PEG soluble support via a carboxylic function at its C-2 position [116]. Unfortunately, this work was performed in a do-... 

Other types of HIV-1 protease inhibitors have also been prepared using microwave-promoted Suzuki reaction [37]. The symmetric cyclic sulfamide (3K,4S,5S,6it)-3,6-bis(phenoxymethyl)-2,7-bis[4-(2-thienyl)benzyl]-l,2,7-thi-adiazepane-4,5-diol 1,1-dioxide, for instance, was synthesized via cross-couphng of (3aS,4R,8it,8aS) - 5,7 - bis(4 - bromobenzyl) - 2,2 - dimethyl - 4,8 - bis-(phenoxymethyl) hexahydro [1,3] dioxolo [4,5 - d] [ 1,2,7 ] - thiadiazepine 6,6 - dioxide with 2-thienylboronic acid for 3 min at 45 W (Scheme 19). 

Heteroarylphenylalanines could be smoothly obtained via microwave-promoted Suzuki reaction of heteroaryl halides with 2-amino-3-[4-(dihy-droxyboryl)phenyl]propanoic acid (Scheme 28) [46]. Interestingly, the free amino acid could be used without any protection of the amine and carboxylic acid fimctionahty. When 4-(dihydroxyboryl)-L-phenylalanine was used as organometallic partner no racemization was observed. The carboxylate anion and free amino group seem to shield the a-C - H from deprotonation and thus hmit racemization. 

The first microwave-promoted Suzuki couplings were reported in 1996 (Eq. 11.20) [17]. Phenyl boronic acid was coupled with 4-bromotoluene to give a fair yield of product after a reaction time of less than 3 min under single-mode irradiation. The same reaction had previously been conducted with a reported reaction time of 4 h. 

Equation (11.21) is an example of a single-mode microwave-promoted Suzuki coupling, delivering a cyclic H IV-protease inhibitor after a subsequent hydrolysis of the ketal group [35], Half a dozen compounds were synthesized with the help of micro-waves and some of the compounds had K, values in the nanomolar range. 

A series of potent, linear C2-symmetric HIV-1 protease inhibitors with K, values in the nanomolar range was prepared from a diaryl bromide precursor emanating from a carbohydrate scaffold, by application of Heck, Suzuki, Stille, and cyanation reactions. Included in this series was the first reported microwave-promoted Suzuki coupling with an alkyl borane [41]. A very high-yielding Suzuki coupling is presented... 

N.E. Leadbeater and R.J. Smith, Real-time monitoring of microwave-promoted Suzuki coupling reactions usin in situ Raman spectroscopy, Org. Lett, 8, 4589 591 (2006). 

The first microwave-promoted Suzuki couplings were published in 1996 (Scheme 44). Phenyl boronic acid was coupled with 4-methylphenyl bromide... 

Scheme 22 Microwave-promoted Suzuki and Heck couplings for comparison of batch and stop flow techniques...

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... 

A highly regioselective microwave promoted synthesis of 2-aryl-6-chloro-benzothiazoles (xxxviii) by the Suzuki-Miyaura coupling reaction of 2,6-dic-hlorobenzothiazole with arylboronic acids is given by Heo et al. [58]. 

Heo Y, Song YS, Kim BT et al (2006) A highly regioselective synthesis of 2-atyl-6-chlorobenzothiazoles employing microwave-promoted Suzuki-Miyaura coupling reaction. Tetrahedron Lett 47 3091-3094... 

Erdelyi, M., Gogoll, A. Rapid Microwave Promoted Sonogashira Coupling Reactions on Solid Phase. J. Org. Chem. 2003, 68, 6431-6434. Najera, C., Gil-Molto, J., Karlstroem, S., Falvello, L. R. Di-2-pyridylmethylamine-Based Palladium Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and Aqueous Solvents. Org. Lett. 2003, 5,1451-1454. 

Potassium aryltrifluoroborates proved to be useful candidates for microwave-promoted Suzuki reactions in aqueous environments (Scheme 1.67). ... 

Another topic often encountered in the literature on microwave-promoted reactions is the lower consumption of energy associated with the use of MW technology in small-scale chemistry. For the palladium-catalyzed Suzuki reaction there have been attempts to investigate this matter in more detail. Clark et al. have performed a comparative study of the energy efficiency of the different reaction techniques. The Suzuki reaction was analyzed and under the reaction conditions used the MW-assisted reaction was 85 times more energy-efficient than the corresponding oil-bath-heated reaction. As there are a multitude of reaction conditions for the Suzuki coupling, this value should be seen as an example, rather than a definite value [20]. 

Bai, L., Wang, J.-X., and Zhang, Y. Rapid microwave-promoted Suzuki cross coupling reaction in water. Green Chem 5, 615-617 (2003). 

Synthesis, characterization and microwave-promoted catalytic activity of novel benzimidazole salt bearing silicon-containing substituents in Suzuki-Miyaura cross-coupling reactions under aerobic conditions was studied by Hasan et al. (2012). 

Scheme 6.32 Microwave promoted Suzuki coupling in water.

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