Suzuki reaction microwave-assisted

Coupling reactions. Microwave assists the Suzuki coupling in aqueous media. A route to biaryl-2-carboxylic acids is via coupling of l-hydroxy-l,2-benziodoxo-3(l//)-one."... 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

A one-pot synthesis of thiohydantoins has been developed using microwave heating [72]. A small subset of p-substituted benzaldehydes, prepared in situ from p-bromobenzaldehyde by microwave-assisted Suzuki or Negishi reactions, was reacted in one pot by reductive amination followed by cyclization with a thioisocyanate catalyzed by polystyrene-bound dimethyl-aminopyridine (PS-DMAP) or triethylamine, all carried out under microwave irradiation, to give the thiohydantoin products in up to 68% isolated yield (Scheme 16). 

The first microwave-assisted Suzuki reactions involving heteroaromatic skeletons were reported in 1996 [35]. Hallberg et al. Hnked the substrates 4-iodo and 4-bromobenzoic acid to a TentaGel-Rink resin (Scheme 16). Suzuki reactions on these soUd-phase-Unked substrates were easily performed in less than 4 min using a constant microwave irradiation power (45 W) (no temperature control Standard acidic cleavage with TEA yielded the corresponding biaryls with an excellent yield. 

Solvent-free microwave-assisted Suzuki reaction on AI2O3 as soHd support using KF as base has also been described in the hterature by Villemin [38] (Scheme 20). Ligand-free Pd(OAc)2 was used as a precatalyst. In a reaction... 

AT-acetyltryptamines could be obtained via microwave-assisted transition-metal-catalyzed reactions on resin bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide. While acceptable reaction conditions for the application of microwave irradiation have been identified for Stille heteroaryla-tion reactions, the related Suzuki protocol on the same substrate gave poor results, since at a constant power of 60 W, no full conversion (50-60%) of resin-bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide could be obtained even when two consecutive cross-coupling reaction cycles (involving complete removal of reagents and by-products by washing off the resin) were used (Scheme 36). Also under conventional heating at 110 °C, and otherwise identical conditions, the Suzuki reactions proved to be difficult since two cross-coupling reaction cycles of 24 h had to be used to achieve full conversion. 

A potentially interesting development is the microwave-assisted transition-metal-free Sonogashira-type coupling reaction (Eq. 4.10). The reactions were performed in water without the use of copper(I) or a transition metal-phosphine complex. A variety of different aryl and hetero-aryl halides were reactive in water.25a The amount of palladium or copper present in the reaction system was determined to be less than 1 ppm by AAS-MS technique. However, in view of the recent reassessment of a similarly claimed transition-metal-free Suzuki-type coupling reaction, the possibility of a sub-ppm level of palladium contaminants found in commercially available sodium carbonate needs to be ruled out by a more sensitive analytical method.25 ... 

A recent publication by the group of Barbarella has disclosed the rapid preparation of poorly soluble unsubstituted and modified a-quinque- and sexithiophenes by the extensive use of bromination/iodination steps and microwave-assisted Suzuki and Sonogashira cross-couplings (Scheme 6.16) [42]. Suzuki reactions were either carried out under solvent-free conditions on a strongly basic potassium fluoride/ alumina support for the synthesis of soluble oligothiophenes, or in solution phase for the preparation of the rather insoluble a-quinque- and sexithiophenes. In both cases, 5 mol% of [l,l -bis(diphenylphosphino)ferrocene]dichloropalladium(II)... 

The synthesis of fully conjugated semiconducting para-phenylene ladder polymers by microwave-assisted palladium-mediated double Suzuki and Stille-type reactions has been demonstrated by Scherf and coworkers (Scheme 6.27) [58], The procedure, which yields polymeric material in ca. 10 min, has no adverse effects on the quality of the polymers and displays a high degree of reproducibility. Compared... 

Further examples of microwave-assisted Suzuki cross-couplings involving supported substrates/catalysts or fluorous-phase reaction conditions are described in Chapter 7. 

For the solution-phase preparation of functionalized tropanylidenes, the authors simply dispensed solutions of the bromo N-H precursor in 1,2-dichloroethane (DCE) into a set of microwave vials, added the aldehydes (3 equivalents) and a solution of sodium triacetoxy borohydride in dimethylformamide (2 equivalents), and subjected the mixtures to microwave irradiation for 6 min at 120 °C. Quenching the reductive amination with water and subsequent concentration allowed a microwave-assisted Suzuki reaction (Section 6.1.2) to be performed directly on the crude products [295]. 

A microwave-assisted Suzuki reaction performed in a microreactor device has been discussed in Section 4.5 [153]. More examples of microwave-assisted transformations involving immobilized catalysts are described in ref. [154]. 

Several microwave-assisted procedures have been described for soluble polymer-supported syntheses. Polyethylene glycol) (PEG)-supported aryl bromides have been shown to undergo rapid palladium(0)-catalyzed Suzuki couplings with aryl boronic acids in water (Scheme 12.16) [63], The reaction proceeded without organic cosolvent... 

Baxendale IR, Griffiths-Jones CM, Ley SV, Tranmer GK (2006b) Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations. Chem Eur J 12 4407-4416 Baxendale IR, Deeley J, Griffiths-Jones CM, Ley SV, Saaby S, Tranmer GK (2006c) A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine a new paradigm for molecular assembly. J Chem Soc Chem Commun 2566-2568... 

He, P. and Heswell, S.J. and Fletcher, P.D.I. (2004). Microwave-assisted Suzuki reactions in a continuous flow capillary reactor. Applied Catalysis A General, 274, 111-114. 

Baxendale IR, Griffiths-Jones CM, Ley S V, Tranmer GK. Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations. ChemEur J 2006 12 4407-4416. 

Lately, a number of papers have dealt with microwave-assisted reactions on palladium-doped A1203. Villemin reported on Stifle, Suzuki, Heck and Trost—Tsuji reactions where potassium fluoride on alumina was used as the base26. The reactions were carried out without solvent or stabilising phosphine ligands in single-mode reactors. The Stifle reactions were noteworthy as the toxic organotin residue remained adsorbed on the solid support, thus allowing a simplified work-up procedure for the otherwise unpleasant, and toxic, stannous by-products. Both the Stifle and the Suzuki reactions could be performed under air. Furthermore, it was noted that with experiments where the... 

Blettner, C.G., Konig, W.A., Stenzel, W. and Schotten, T., Microwave-assisted aqueous Suzuki cross-coupling reactions, /. Org. Chem., 1999,64, 3885. 

We have subsequently revisited this reaction and successfully optimized the Suzuki microwave-assisted coupling conditions using the Smith synthesizer. Several parameters were investigated, including the palladium catalysts, the reaction temperatures, and the reaction times (Table I). Optimization reactions were run in the Smith synthesizer using 50 mg of resin 7 and 6 equivalents of 4-methoxyphenylboronic acid to afford oxa-zolidinone 8. In just a few days, optimized conditions were identified that afforded the desired product in excellent yields and purities with reactions times of only 5-10 min.8... 

E. Van der Eycken et al. explored a microwave-assisted Suzuki-Miyaura reaction to generate structural analogues of the apogalanthamine family... 

It is noteworthy that the microwave-assisted Suzuki-Miyaura reactions were found to be far superior to the reactions under conventional heating, as can be demonstrated by yield improvements from 22% to 84% in the case of cross-coupling of PEA derivatives. Microwave-irradiation also provided smooth conversions in water as the sole solvent. 

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