Domino Reactions under Microwave Heating

Intramolecular Domino Reactions under Microwave Heating 

The development of new Diels-Alder (DA) reactions has been actively pursued in the past several decades because they can readily provide an atom-economic access to a wide spectrum of biologically relevant compounds [19]. Moreover, the integration of DA reactions in a domino process and under microwave irradiation is a very fruitful procedure. 

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Intramolecular Domino Reactions under Microwave Heating... 

In another report, 1,5-benzodiazepines have been obtained from reaction of alk-3-yn-l-ones with 1,2-phenylenediamines in ethanol under microwave heating without the need for any catalyst (14GC1120). A palladium-catalyzed domino reaction between 1,2-phenylenediamines and 10,11-dihydro-5H-dibenzo[fc,e][l,4]diazepines starting from 2-bromobenzyl bromides has also been developed (14EJ04773). 

Subsequently, Mane and coworkers [31] reported a domino synthesis of pyrazolo[3,4-i)]quinolines 37 by carrying out the condensation of 2-chloro-3-formyl quinolines 35 with hydrazine hydrate/phenyl hydrazine 36 under microwave heating in water (Scheme 12.13). The reaction was accomplished in 2.5 h with yields of93-97%. The same reaction took 7 h at 100 °C under conventional heating. 

These reactions employ microwave heating and water as the reaction medium at 100 °C for 7-9 min. The mechanism for diastereoselectivity was confirmed by density functional theory (DFT) (B3LYP) calculations. Subsequently, new multicomponent domino reactions of Meldrum s acid 159, aromatic aldehydes 69, and electron-rich heteroaryl-amines 80 have been established for the synthesis of spiro pyrazolo[l,3]dioxanes-pyridine -4,6-diones and spirojisoxazolo [l,3]dioxanes-pyridine -4,6-diones 160 in aqueous solution under microwave irradiation (Scheme 12.64) [88]. A total of 26 examples were examined to show the broad substrate scope and high overall yields (76-93%). A new mechanism was proposed to explain the reaction process and the resulting chemo-, regio-, and stereoselectivity. 

See, for instances (a) S. Santra, R R. Andreana, Org. Lett. 2007, 9, 5035-5038. A one-pot, microwave-influenced synthesis of diverse small molecules by multicomponent reaction cascades, (b) M. Presset, Y. Coquerel, J. Rodriguez, Org. Lett. 2009, 11, 5706-5709. Microwave-assisted domino and multi-component reactions with cyclic acyUcetenes expeditious syntheses of oxazinones and oxazindiones. (c) W.-J. Hao, B. Jiang, S.-J. Tu, X.-D. Cao, S.-S. Wu, S. Yan, X.-H. Zhang, Z.-G. Han, F. Shi, Org. Biomol. Chem. 2009, 7,1410-1414. A new mild base-catalyzed Mannich reaction of hetero-arylamines in water highly efficient stereoselective synthesis of 3-aminoketones under microwave heating, (d) P. Nun, J. Martinez, F. Lamaty, Synthesis 2010, 2063-2068. Microwave-assisted neat procedure for the Petasis reaction. 

In order to study any chemoselectivity influences of microwave irradiation on the domino Knoevenagel/hetero-Diels-Alder process (the so-called Tietze reaction), Raghunathan and coworkers [31a] investigated the transformation of 4-hydroxy coumarins (10-85) with benzaldehydes 10-86 in EtOH to afford pyrano[2,3-c]cou-marin 10-87 and pyrano[2,3-b]chromone derivatives 10-88. Normal heating of 10-85a and 10-86a at reflux for 4h gave a 68 32 mixture of 10-87a and 10-88 in 57% yield, whereas under microwave irradiation a 97 7 mixture in 82% yield was obtained. Similar results were found using the benzo-annulated substrates 10-85b and 10-86b. 

An intermolecular approach to carbazoles 273 was reported via an inverse electron-demand Diels-Alder reaction between 3-chloroindoles 271 and pyrones 272. This reaction proceeds through a thermally induced Diels-Alder, decarboxylation, elimination-domino process. Heating the two components under microwave irradiation generates carbazoles with methyl esters in the 3-position in a completely regioselective manner (140L1124). 

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