Microwave irradiation, aryl

Keywords aryl iodide, terminal alkyne, Sonogashira coupling, KF-alumina, microwave irradiation, aryl alkyne... 

Keywords dimethoxybenzene, diethyl azodicarboxylate, InCl3-Si02, microwave irradiation, aryl hydrazine... 

Keywords aromatic aldehyde, primary amine, malonic acid monoethyl ester, Rodionov reaction, microwave irradiation, / -aryl-/ -amino acid ester, ethyl cinna-mate... 

Microwave irradiation Aryl iodides, bromides, and triflates Dramatic rate enhancement [89, 217-220]... 

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... 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Scheme 78) [89]. Aryl chlorides with activating as well as deactivating substituents could also be coupled under the same conditions in high yields, ranging from 60% to 95%, within 30-60 min of microwave irradiation. The process does not require an inert atmosphere. The increased conversion observed with the addition of the ionic liquid reveals that it might have an additional function besides simply acting as a molecular irradiator . It cannot be excluded for instance that carbene palladium complexes are formed in situ and implicated in the catalytic cycle. 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

N-Arylpiperazin-2-ones, N-arylpiperazin-2,5-diones and N-aryl-3,4-dihydro-quinolin-2(lff)-ones have been synthesized via a microwave-enhanced Goldberg reaction [105]. N-arylation reactions with 4-benzylpiperazin-2-one and 4-benzylpiperazin-2,5-dione performed in the microwave (reflux conditions) were tremendously accelerated in comparison with the same transformations performed under classical heating at reflux (Schemes 103 and 104). The phenylation of 3,4-dihydroquinolin-2(lH)-one under microwave irradiation was also faster but less pronounced. 

The last method for the preparation of 2-quinolones described in this chapter relies on a intramolecular Heck cyclization starting from heteroaryl-amides (Table 2) [57]. These are synthesized either from commercially available pyrrole- and thiophene-2-carboxylic acids (a, Table 2) or thiophene-and furan-3-carboxylic acids (b, Table 2) in three steps. The Heck cyclization is conventionally performed with W,Ar-dimethylacetamide (DMA) as solvent, KOAc as base and Pd(PPh3)4 as catalyst for 24 h at 120 °C resulting in the coupled products in 56-89% yields. As discussed in Sect. 3.4, transition metal-catalyzed reactions often benefit from microwave irradiation [58-61], and so is the case also for this intramolecular reaction. In fact, derivatives with an aryl iodide were successfully coupled by conventional methods, whereas the heteroarylbromides 18 and 19, shown in Table 2, could only be coupled in satisfying yields by using MAOS (Table 2). 

Using a conventional dorm-room quality microwave oven, we have successfully performed Suzuki-Miyaura cross-coupling reactions catalyzed by Pd/C. Shorter reaction times are obtained (13 min of irradiation) using microwave irradiation compared to conventional methods of heating (> 1 h). Yields with relatively non-volatile aryl bromides range from 65 to 83%. Lower yields (15 - 27%) are obtained with relatively volatile aryl bromides substrates which may be evaporating during the course of the reaction. Ease of reaction set-up, rate enhancement from the microwave irradiation and facile work-up provided by the use of Pd/C makes this a very efficient procedure to mn. 

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