Cydoaddition solvent-free

In 2001, Linder and Podlech studied the microwave-assisted decomposition of diazoketones derived from a-amino acids [340]. In the presence of imines, the initially formed ketene intermediates reacted spontaneously by [2+2] cydoaddition to form /3-lactams with a trans substitution pattern at positions C-3 and C-4 (Scheme 6.179) [340], In order to avoid the use of the high-boiling solvent 1,2-dichlorobenzene, most transformations were carried out in 1,2-dimethoxyethane under sealed-vessel conditions. Solvent-free protocols, in which the substrates were adsorbed onto an inorganic alumina support, led only to the corresponding homologated /3-amino acids. Evidently, traces of water present on the support trapped the intermediate ketene. 

The 1,3-dipolar cycloaddition of azides to alkynes is a versatile route to 1,2,3-tri-azoles. Different combinations of substituents on the azide and on the alkyne allow the preparation of diverse N-substitutcd 1,2,3-triazoles. Katritzky and Singh have described the synthesis of C-carbamoyl-1,2,3-triazoles by microwave-induced cydoaddition of benzyl azides to acetylenic amides (Scheme 6.220) [393]. Employing equimolar mixtures of the azide and alkyne under solvent-free conditions, the authors were able to achieve good to excellent isolated product yields by microwave heating at 55-85 °C for 30 min. In general, the triazole products were obtained as mixtures of regioisomers. Control experiments carried out under thermal (oil bath)... 

In contrast with the results of Langa et al. on the cydoaddition reaction to C70, MW irradiation had no effect on the regioselectivity of the reactions in polar solvents, but a substantial effect was observed both in the nonpolar solvent, xylene and under solvent-free conditions. In polar solvents (pentanol and DMF) the ratio of products 64, 65, and 66 was 95 5 0 under both MW and conventional heating. In xylene and in the absence of solvent the ratio of isomers changed from 32 28 40 (xylene) and 36 27 27 (no solvent) under conventional heating to 100 0 0, i. e. totally regioselec-tive, under MW activation. 

Loupy et al. [73] described the reaction of 1-ethoxycarbonylcydohexadiene (I) and 3-ethoxycarbonyl-a-pyrone (II) under solvent-free conditions - an irreversible Diels-Alder cydoadditions with an acetylenic compound. Because a spedfic micro-wave effect was apparent for compound II only (Fig. 4.9), it was concluded that higher yields are related to variation of the dipole moment from the ground state GS to the transition state TS. These condusions are supported by results from ab initio calculations (Table 4.8). 

Some excellent results for cycloadditions involving nitrones were observed by Merino et al. [99] using a solvent-free [3+2] cydoaddition of N-berrzyl-C-glycosyl nitrones to methyl acrylate. Microwave irradiation for 0.1 h was sufficient to afford a 100% yield of the isolated isoxazolidine whereas thermal heating under reflux conditions (80 °C) required 0.5 h and produced the same yield and the same stereoisomeric ratio. 

Microwave-induced 1,3-dipolar cydoaddition reactions involving azomethine ylides have been widely reported in the literature. In 2002 many examples were described in a book chapter by de la Hoz [3j], which provides extensive coverage of the subject. The objective of this section is to highlight some of the most recent applications and trends in microwave synthesis, and to discuss the impact of this technology. Highly stereoselective intramolecular cycloadditions of azomethine ylides have been performed under solvent-free microwave conditions. 

Bashiardes et al. reported a study involving cydoaddition of O-allylic or O-propargylic salicylaldehydes 152 or 153 to a-amino esters 154 treated under different conditions toluene at reflux (A) conventional heating without solvent (B) or microwave irradiation under solvent-free conditions (C) (Scheme 11.38) [lOOj. The cydoaddition reaction involves polar 1,3-dipolar azomethine ylide intermediates 155 and 156. The best results were obtained in a one-pot procedure under micro-wave conditions providing pyrrolidines 157 or pyrroles 158 in excellent yields ranging from 70 to 98% at 130 °C for 5-30 min. 

Systematic examination of the [2+2] cydoaddition reactions of jS-formyl enamides with alkynes with use of microwave technology has been performed only recently. Novel utility of j8-formyl enamides 231 in cydoaddition with acetylenic dienophiles 232, solvent-free on basic alumina, under the action of microwave irradiation was reported by Boruah et al. (Scheme 11.59) [117]. Indeed, the desired steroidal oxe-tenes 233 were obtained in 70-80% yields under the optimized conditions (1 equiv. 231, 1.5 equiv. 232, and 2 equiv. triphenylphosphine for 5 min). Conventional heating in a protic solvent for 72 h led to very poor yields (15-23%) of oxetenes 233. 

H. Kang, H.J. Lee, J.C. Park, H. Song, K.H. Park, Solvent-free microwave promoted [3 + 2] cydoaddition of alkyne-azide in uniform CuO hollow nanospheres. Top. Catal. 53 (2010) 523-528. 

A gallium(III) triflate-catalyzed [4 + 3] cydoaddition of 1,3-diarylpropanones and OPD has been developed for the synthesis of 2,4-disubstituted-3H-benzo[b][l,4]diazepines using ethanol as a green solvent at room temperature. The product was collected by filtration and the catalyst was directly used for the next cycle. The process was repeated 10 times and the catalyst was found to maintain consistent activity [104,105]. Several approaches to benzodiazepinone and benzothiazepine ring systems xmder solvent-free conditions and using other greener techniques such as MW, US or solid acid catalysis, organocatalysis, and so on are also known [106,107]. 

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