Aryl 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-... 

Using a different catalytic system, the Larhed group was able to perform regio-selective microwave-promoted chelation-controlled double-/3-arylations of terminal alkenes (Scheme 6.5) [24]. In this Heck approach, the authors used vinyl ethers as chelating alkenes and aryl bromides as coupling partners, employing Herrmann s... 

Microwave promoted, palladium-catalyzed, DPPP-controlled arylation of butyl vinyl ether with 4-tert-butylphenyl triflate afforded the branched arylation product and the corresponding methyl ketone, indicating the occurrence of selective internal a-arylation. Addition of water to the reaction mixture and microwave-heating for 2.8 min at 55 W smoothly produced the hydrolyzed product, 4-tert-butylacetophe-none, with an isolated yield of 77% (Eq. 11.2) [17]. 

The use of ionic liquids in microwave chemistry has great potential and a number of research groups have introduced the use of ionic liquids in synthetic approaches43,44. l-Butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) was recently evaluated as a solvent for the microwave-promoted Heck reaction45. Terminal arylations of electron-poor olefins were carried out rapidly with good-to-excellent yields, using the old-fashioned catalyst palladium chloride (Scheme 2.15). As an example, the... 

The concept of in situ liberation of carbon monoxide would be even more attractive if a metal-free material could serve as the carbon monoxide source. In the ideal carbonylation method, the organic solvent itself could be exploited for controlled generation of carbon monoxide. In 2002, Wan et al. addressed this issue and developed a microwave-promoted carbamoylation process based on the commonly used solvent dimethylformamide (DMF) as the carbon monoxide precursor75. Firstly, it was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of a nucleophilic catalyst, imidazole (Scheme 2.34). Secondly, tertiary benzamides other than dimethylamides were synthesised by addition of 3 equiv of an external amine (Scheme 2.34). 

Zhang, A. and Neumeyer, J.L., Microwave promoted Pd-catalysed cyanation of aryl triflates a fast and versatile access to 3-cyano-3-desoxy-10-ketomorphinans, Org. Lett., 2003, 5, 201-203. 

Arvela, R.K., Leadbeater, N.E., Torenius, H.M. and Tye, H., Rapid cyanation of aryl iodides in water using microwave promotion, Org. Biomol. Chem., 2003,1, 1119-1121. 

Scheme 1 Microwave-promoted synthesis of N-aryl pyrrolidines in neat water...

This review attempts to provide an overview of microwave-promoted metal-catalyzed transformations of aryl and vinyl halides (or pseudo halides), providing a personal selection of both pioneering and very recently published work. Covered areas include carbonylative transformations, Heck and Sono-gashira reactions, nucleophilic substitutions and cross-couplings. Because of the diversity of the microwave systems used, the reader should consult the original references for detailed descriptions of settings and instrumentation. 

Scheme 1 Microwave-promoted aminocarbonylations of aryl chlorides using Mo(CO)g as a solid carbon monoxide source...

In the last few years numerous reports have been published in the field of microwave-promoted aryl halide cyanation, utilizing nickel [71], palladium [72,73] and copper [74,75] catalysis. Even water [75] and ionic liquids [76] have proven useful as solvents in these processes. Srivastava and Collibee have exemplified a swift and dynamic procedure using polymer-supported triphenyl phosphine to enable easy subsequent removal through filtration [72]. As shown in Scheme 19, both bromides and iodides could be activated using palladium catalysis in DMF. Even without optimization of the individual reaction times, the overall process time involving simple filtration and extraction for compound isolation appears to be short. 

Aryl chlorides are more reluctant to participate in amination than most other aryl halides/pseudohalides. To tackle this problem, Caddick et al. examined the effect of palladium-N-heterocyclic carbenes as catalysts in rapid microwave-promoted reactions [87]. Para-tolyl and -anisyl chloride were reacted with aromatic and aliphatic amines in mostly good yields within 6 minutes of heating at 160 °C. Reactions using anisyl, tolyl or phenyl chlorides and aliphatic amines have also been reported by Maes et al. using a phosphine ligand and a strong base, which creates the desired products after 10 minutes of heating at 110-200 °C [88]. 

In a separate project, methods for microwave-assisted generation of Grig-nard reagents from aryl chlorides and aryl bromides were developed [81]. One of the aryl magnesium bromides generated was used with the unsymmetric 42, 2% Pd2(dba)3 and 4% [ t-Bu3PI I ]BF4 in a microwave-promoted Kumada coupling to provide 46 in 67% isolated yield, a compound unfortunately found to be a relatively poor HIV-1 protease inhibitor (Scheme 21). 

Dihydroisocoumarin is accessible from a microwave promoted palladium-catalyzed reaction of the aryl bromide 1153 with Mo(CO)6 as a source of carbon monoxide (Equation 445) <2004TL4635>. 

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]. 

Lewis JC, Wu JY, Bergman RG, EUman JA (2006) Microwave-promoted rhodium-catalyzed arylation of heterocycles through C-H bond activation. Angew Chem Int Ed 45 1589-1591... 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins organohalides or pseudohalides are frequently used as organopalladium precursors [143]. One of the strengths of the method is that it enables direct mono-functionalization of a vinylic carbon, which is difficult to achieve by other means. The Heck arylation in Scheme 15.74, reported in 1996, was the first example of a microwave-promoted, palladium-catalyzed C-C bond formation [18]. The power... 

The use of microwave technology in synthesis continues to gain popularity. A microwave-enhanced synthesis of 3-aryl-4-hydroxyquinolin-2(l//)-oncs by cyclization of a malonodianilide under solvent free conditions was reported <01TL1367>. Microwave irradiation was also used to prepare quinolones from anthranilic acid and ketones <01SC3647>. A microwave promoted, intramolecular cyclization of an isocyanate in the ortho position of a stilbene derivative to afford a quinolone derivative was also reported <01T6197>. 

The microwave-promoted arylation of heterocyclic compounds by C-H activation was also reported. It was found that the use of 9-cyclohexylbicyclo[4.2.1]-9-phosphanonane as a ligand was critical in obtaining high yields. With this ligand, aryl bromides were efficiently coupled to a variety of heterocyclic compounds as compared with other catalyst systems that are prone to cause hydrodehalogenation. 

Svennebring, A., Nilsson, P. and Larhed, M. (2004) Microwave-promoted and chelation-controlled double arylations of terminal olefinic carbon of vinyl ethers. J. Org. Chem., 69, 3345-9. 

More recently, a microwave-promoted palladium-catalyzed aminocarbonyla-tion of (hetero)aryl halides (X = I, Br, Cl) using Mo(CO)e and allylamine as a nucleophile was also described [190, 191]. Remarkably, no side products resulting from the competing Heck reaction were detected. Importantly, this was the achievement that aminocarbonylation was realized on a larger laboratory scale (25 mmol) starting from 4-iodoanisole (Scheme 2.18). 

Larhed s group developed the microwave-promoted aminocarbonylation of aryl chlorides using Mo(CO)e as a solid carbon monoxide source [226-228]. This procedure offers aryl chlorides that rapidly transformed into a variety of benzamides (Scheme 2.29). Noteworthy features of this microwave method include the use of commercially available [(f-Bu)3P]HBF4 to activate the strong Ar-Cl bond impressive results with sluggish aniline and ferf-butylamine reactants air tolerance short reaction times and the use of Mo(CO)g as a solid carbon monoxide source. 

Under mild conditions (1-4 bar CO, 25-60 °C), high yields of the desired produets were produced. Benzyl, allyl, aryl, and vinyl halides containing primary, secondary, or tertiary aleohol groups were readily converted to a variety of lactones, including phthalides and butenolides (Scheme 2.160a). Sinee then, 2-bromo benzyl aleohol has been tested as a substrate in various systems, such as carbonylation with a flow microreactor,[ C]-labelled compounds, and microwave-promoted with Mo(CO)g as a carbon monoxide source (Scheme 2.160b). Cobalt carbonyl as a cheaper catalyst was also applied in the intramolecular cyclization of aryl halides (Scheme 2.160c). ... 

In 2008, Marsden and coworkers [86] extended the paUadium-cattilyzed intramolecular arylation of o-haloanilides to the synthesis of valuable quaternary 3-aminooxindole molecules. Specifically, these compounds were prepared by the rapid microwave-promoted intramolecular arylation of A7-(2-bromophenyl)-A/ -methyl-2-dialylaminoacylamines, in the presence of NaOtBu as the base and a... 

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