Microwave -catalyzed

The Diels-Alder reaction of 2H-pyran-2-ones part IV - Microwave catalyzed Diels-Alder reaction of 4,6-disubstituted-2H-pyran-2-ones with 1,4-naphthoquinone and N-phenylmaleimide [41a]... 

Owens, J. R., Hayn, R. A., Boyer, S. A. and McDonald, R. S. 2008. Synthesis of hydrophobic and oleophobic nylon-cotton fabric through microwave catalyzed silane attachment. http //www.dtic.mil/cgi-bin/GetTRDoc AD=ADA494410 Location=U2 doc=GetTRDoc.pdf [accessed 25 October 2011]. 

Implants are coated with hydroxyapatite to obtain biomimetically grown hydroxyapatite coating. The number of nucleation sites in HA composition is important not with the focus of speeding up the process, but to increase the coating adhesion and/or to change the textrrre and morphology of the coating. The microwave catalyzes the HA nucleation and results in the faster HA crystal formation. ... 

Other PK variations include microwave conditions, solid-phase synthesis, and the fixation of atmospheric nitrogen as the nitrogen source (27—>28). Hexamethyldisilazane (HMDS) is also an excellent ammonia equivalent in the PK synthesis. For example, 2,5-hexanedione and HMDS on alumina gives 2,5-dimethylpyrrole in 81% yield at room temperature. Ammonium formate can be used as a nitrogen source in the PK synthesis of pyrroles from l,4-diaryl-2-butene-l,4-diones under Pd-catalyzed transfer hydrogenation conditions. 

Microwave chemistry has been found to be a useful method for accelerating reactions or catalyzing reactions that are difficult to carry out by other methods. A modification of the Hantzsch method to directly obtain pyridines has been communicated. A dry medium using ammonium nitrate bentonitic clay system with microwave irradiation affords pyridines 96 in a single pot within 5 minutes. When the pyridine is not the major product (> 75% yield), the dealkylated pyridine 97 becomes an... 

Metallocenes Mg(II)-catalyzed Microwave irradiation MO calculation Montmorillonite Moraceous plants Morphinadienes Mulberry tree Multifunctional catalysis Multi-step... 

Microwave-Assisted Transition Metal Catalyzed Coupling Reactions... 

Halogen-substituted 2-pyridones are key intermediates for further metal-catalyzed coupling reactions and the halogenation of these scaffolds has already been described in previous sections. In the following section, a variety of C - C and C - N cross-coupling reactions under microwave-assisted conditions are described with some illustrative examples. 

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... 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

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. 

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). 

A microwave-assisted three-component reaction has been used to prepare a series of 1,4-disubstituted-1,2,3-triazoles with complete control of regiose-lectivity by click chemistry , a fast and efficient approach to novel functionalized compounds using near perfect reactions [76]. In this user-friendly procedure for the copper(l) catalyzed 1,3-dipolar cycloaddition of azides and alkynes, irradiation of an alkyl halide, sodium azide, an alkyne and the Cu(l) catalyst, produced by the comproportionation of Cu(0) and Cu(ll), at 125 °C for 10-15 min, or at 75 °C for certain substrates, generated the organic azide in situ and gave the 1,4-disubstituted regioisomer 43 in 81-93% yield, with no contamination by the 1,5-regioisomer (Scheme 18). 

Scheme 25). The introduction of greater diversity at C-2 and C-4 can be achieved by intercepting the tetrahydropyridinone intermediate in a multi-step sequence involving C-2 ammonolysis, microwave-assisted N-acylation, acid-catalyzed cyclization (to introduce diversity at C-2), treatment with POCI3, and either microwave-assisted nucleophiUc substitution or Suzuki couphng (to introduce diversity at C-4) [89]. 

A solvent-free strategy for the synthesis of thiazoles involved mixing of thioamides with a-tosyloxy ketones in a clay-catalyzed reaction (Scheme 7). The typical procedure entailed mixing of thioamides and in situ produced a-tosyloxy ketones with montmorillonite K-10 clay in an open glass container. The reaction mixture was irradiated in a microwave oven for 2-5 min with intermittent irradiation and the product was extracted into ethyl acetate to afford 2-substituted thiazoles in 88-96% yields [8]. 

Kurth et al. applied an analogous strategy for the preparation of hydan-toins via base-catalyzed microwave-mediated carbanibde cychzation however, in their study the reactions were run without temperature/pressure control and will therefore not be discussed in further detail [59]. 

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

Early 2005, Leadbeater s team reported that the previously claimed tran-sition-metal-free Suzuki-type protocol was definitely palladium-catalyzed [ 53 ]. Palladium contaminants down to the level of 50 ppb found in commercially available sodium carbonate were responsible for the generation of the biaryl. For good product yields in a short reaction time under microwave irradiation, a loading of 1 ppm Pd was required. 

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 microwave-assisted Cu-catalyzed Sonogashira-type protocol on aryl iodide substrates without the involvement of a palladium catalyst has also been published (Scheme 54) [71]. Reactions were executed using Cut and CS2CO3 in NMP at 195 °C. The application seems to be fairly limited since there are indications that only (hetero)arylacetylenes are suitable coupHng partners for this protocol. In addition, aryl bromides react more sluggishly than aryl iodides. Moreover, even on aryl iodides the reaction times required are on the order of hours. 

A heterogeneous variant of the rapid microwave assisted homogeneous Pd-catalyzed cyanation process of Alterman and Hallberg was developed by Srivastava and Collibee (Schemes 67 and 68) [80]. The heterogeneous cat-... 

Independently, Antane reported that arylisonipecotic acids were obtained from aryl bromides in a two-step process involving microwave-assisted palladium-catalyzed amination with ethyl isonipecotate followed by ester hydrolysis with KOH (Scheme 91) [96]. Interestingly, toluene, which is the standard solvent for Buchwald-Hartwig aminations under conventional heating, was used as the sole reaction medium, although it is a very weak... 

Oxazol-4-ones 132 have been prepared by Trost and co-workers via a microwave-assisted cyclocondensation of bromo imides in the presence of NaF [86]. These products where then employed for a Mo-catalyzed asymmetric synthesis of Q -hydroxycarboxylic acid derivatives 134 (Scheme 47). 

Benzoxazine, an heterocycle present as structural subunit in many naturally occurring and synthetic bioactive compounds, was prepared under microwave irradiation from a mixture of 2-aminophenol 218 and an a-bromoester 219 (Scheme 80). The reaction proceeded through an initial base-catalyzed alkylation of the phenoUc OH followed by spontaneous amidation. Yields from 44 to 78% were reported for 17 different benzoxazines 220 [ 141]. 

Abstract An overview on the microwave-enhanced synthesis and decoration of the 2(lH)-pyrazinone system is presented. Scaffold decoration using microwave-enhanced transition-metal-catalyzed reactions for generating structural diversity, as well as the conversion of the 2(lH)-pyrazinone skeleton applying Diels-Alder reactions to generate novel heterocyclic moieties are discussed. The transfer of the solution phase to polymer-supported chemistry (SPOS) is also described in detail. 

The dechlorination of the C-3 and C-5 position of the pyrazinone system was described to be fast under microwave irradiation [29]. Contrary to the reported de-chlorination [26] via palladium-catalyzed reaction with sodium formate 100 °C for 2-4 h and at the C-5 position in 2-3 days, a dramatic rate enhancement was observed under microwave irradiation (Scheme 12). The mono-reduction at C-3 was performed at 190 °C in DMF in merely 5 min, and the reduction of C-5, starting from the mono-reduction product, was performed in n-butanol in 55 min to afford the fois-reduction product in good overall yield. 

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