Microwave irradiation dienes

The investigation on the use of K-10 montmorillonite under free solvent conditions was then extended to inner ring dienes such as furan and its 2,5-dimethyl derivative [9] (Table 4.3). The cycloadditions generally proceed slowly, and Zn(II)-doped clay and microwave irradiation were used to accelerate the reactions. The reaction with maleic anhydride preferentially affords the thermodynamically favored exo adduct. 

The reactive compound chlorosulfonyl isocyanate (ClSOaNCO, forms P-lactams even with unactivated alkenes, as well as with imines, allenes, conjugated dienes, and cyclopropenes. With microwave irradiation, alkyl isocyanates also... 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

A pyran ring is formed in the intramolecular Diels-Alder cycloaddition of alkene-tethered enantiopure (lS,2R)-l,2-dihydroxycyclohexa-3,5-diene-l-carboxylic acid derivatives (derived from the biodihydroxylation of benzoic acid). For the three cases illustrated in Scheme 6.246, Mihovilovic and colleagues found that moderate to high yields of the desired cycloadducts could be obtained by exposing a solution of the precursor to microwave irradiation at 135-210 °C for extended periods of time... 

Cycloaddition reactions often require the use of harsh conditions such as high temperatures and long reaction times. These conditions are not compatible with sensitive reagents or products such as natural products. The applicability of Diels-Alder cycloadditions is, moreover, limited by the reversibility of the reaction when a long reaction time is required. The short reaction times associated with microwave activation avoid the decomposition of reagents and products and this prevents polymerization of the diene or dienophile. All these problems have been conveniently solved by the rapid heating induced by microwave irradiation, a situation not accessible in most classical methods. With the aid of microwave irradiation, cydoaddition reactions have been performed with great success [9, 10]. 

Pyrazole derivatives are very reluctant to participate as dienes in Diels-Alder cycloadditions that involve the pyrazole ring, because of the loss of aromatic character during the process [79]. Microwave irradiation under solvent-free conditions, however, induces pyrazolyl 2-azadienes 96 to undergo Diels-Alder cycloadditions with ni-troalkenes 97 and 98 in 5-10 min to give good yields of pyrazolo-[3,4-b]-pyridines (Scheme 9.29) [80], Under the action of classical heating only traces of the corresponding cycloadducts were detected. 

Examples of the use of heterodienophiles under the action of microwave irradiation are not common. Soufiaoui [84] and Garrigues [37] used carbonyl compounds as die-nophiles. The first example employed solvent-free conditions the second is an example of the use of graphite as a susceptor. Cycloaddition of a carbonyl compound provided a 5,6-dihydro-2H-pyran derivative. These types of reaction proceed poorly with aliphatic and aromatic aldehydes and ketones unless highly reactive dienes and/or Lewis acid catalysts are used. Reaction of 2,3-dimethyl-l,3-butadiene (31) with ethyl glyoxylate (112) occurred in 75% yield in 20 min under the action of microwave irradiation. When conventional heating is used it is necessary to heat the mixture at 150 °C for 4 h in a sealed tube to obtain a satisfactory yield (Scheme 9.33). 

This alkylation reaction can be applied to intramolecular alkylation affording cyclic products, as shown in Equations (19)-(21). The reaction of 2-vinylpyridines with 1,5- or 1,6-dienes results in the formation of five- or six-membered carbocycles with good efficiency.20,20a,20b In addition to pyridine functionality, oxozole and imidazole rings can be applied to this intramolecular cyclization. When the reaction is conducted in the presence of a monodentate chiral ferrocenylphosphine and [RhCl(coe)2]2, enantiomerically enriched carbocycles are obtained. A similar type of intramolecular cyclization is applied to TV-heterocycles. The microwave irradiation strongly... 

Andreana and Santra have investigated the influence of the solvent on the generation of molecular diversity arising from a set of MCR substrates under microwave irradiation [36]. They have found that by using water as solvent, both 2,5-DKPs and 2-azaspiro[4.5]deca-6,9-diene-3,8-diones were obtained through aza-Michael reaction and 5-exo Michael cyclization, respectively. Nevertheless,... 

The Pechmann and Knoevenagel reactions have been widely used to synthesise coumarins and developments in both have been reported. Activated phenols react rapidly with ethyl acetoacetate, propenoic acid and propynoic acid under microwave irradiation using cation-exchange resins as catalyst <99SL608>. Similarly, salicylaldehydes are converted into coumarin-3-carboxylic acids when the reaction with malonic acid is catalysed by the montmorillonite KSF <99JOC1033>. In both cases the use of a solid catalyst has environmentally friendly benefits. Methyl 3-(3-coumarinyl)propenoate 44, prepared from dimethyl glutaconate and salicylaldehyde, is a stable electron deficient diene which reacts with enamines to form benzo[c]coumarins. An inverse electron demand Diels-Alder reaction is followed by elimination of a secondary amine and aromatisation (Scheme 26) <99SL477>. 

Diels-Alder cyclizations are thermal reactions, and recent significant developments in the use of microwave irradiation to pyridine synthesis have been reported, including a series of pyrazolo[3,4- ]pyridines from nitroalkenes and pyrazolylimines with reaction times of 5-10min (Equation 115) <2000T1569>. This method appears to be general to this bicyclic class for example, replacement of the substituent on the imine allows for a C-2-unsubstituted pyridine. A range of cyclic and acyclic dienes have also been reported. 

RCM of diallyltosylamide and related dienes in a CH2C12 solution doped with ionic liquid with microwave irradiation low conversion, probably due to catalyst decomposition. 

Andreana and co-workers [188] developed a one-pot method for generating molecular diversity via a multicomponent coupling reaction under microwave irradiation. The initially formed Ugi four-component coupling products gave rise to three structurally distinct scaffolds depending on the solvent effects and sterics the 2,5-diketopiperazines 137, the 2-azaspiro[4.5]deca-6,9-diene-3,8-diones 138, and the thiophene-derived Diels-Alder tricyclic lactams 139 (Scheme 107). 

It was first reported in 1996 that indium trichloride catalyzes the Diels-Alder reaction in water [131]. The reaction of acrolein with cyclopentadiene in the presence of 20 mol% InCl proceeds stereoselectively (endo. exo=91 9) (Scheme 8.101). Without catalyst the reaction only goes to 60% completion (endo exo=74 26). The InCh-catalyzed Diels-Alder reaction works with either cyclic or non-cyclic dienes. InCh can be recovered for reuse after the reaction is completed. Indium triflate is also an effective catalyst for intramolecular Diels-Alder reactions of furans under microwave irradiation (Scheme 8.102) [132]. 

The Diels-Alder reaction between cycloalkanones (155) and cyclic dienes (154) in toluene and catalyzed by AICI3 under the action of microwave irradiation was reported by Reddy [88]. Reactions were performed in a domestic microwave oven and gave adducts in good yields within 2 min (Scheme 5.44). Interestingly, it was also observed that microwave irradiation increased selectivity for the endo product. This result is in contrast with that reported by Gedye [89] in the cydoaddition of cyclopentadiene with methyl acrylate in methanol. In this reaction, significant modification of endo/ exo selectivity, in comparison with previously reported results, was not observed. 

Under solvent-free conditions with microwave irradiation. Moody et al. have improved the hetero Diels-Alder reaction of eneacylamines with l-alkoxy-2-aza-1,3-dienes [67]. A mixture of l-(2-thiazolyl)-l-acetylaminoethylene 54 and the starting 2-aza-l,3-diene 55, irradiated in a GEM Focused Synthesizer at 180 °C for 15 min produced a 64% yield of adduct 56 (Scheme 11.16). Carboxylic acid esters and thiazole rings are tolerated under these reaction conditions (Scheme 11.16). Without microwave irradiation yields were in the range 25 to 42% [67]. 

Another interesting example of the use of o-QDM as diene was reported by Delgado et al. [69]. The first DA cycloaddition of o-QDM 58 to ester-functionalized single-wall carbon nanotubes (SWNT) 61 was performed in accordance with to Scheme 11.18. The authors showed that such DA reactions could be performed very efficiently in o-dichlorobenzene (o-DCB) under the action of microwave irradiation at 150 W for 45 min (Scheme 11.18). Conventional heating in o-DCB under reflux required 72 h and resulted in less conversion. 

In the past few years solvent-free DA reactions have been regularly performed successfully under microwave irradiation conditions, reducing reaction times to a few minutes compared with several hours under conventional reflux conditions [3j]. Scheme 11.3, mentioned above, shows two recent examples of Diels-Alder cycloadditions performed by microwave dielectric heating [42, 43]. In both examples the diene and dienophile were reacted neat under solvent-free conditions. 

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