Multicomponent Reactions Under Microwave Irradiation Conditions

Multicomponent Reactions Under Microwave Irradiation Conditions 

Tijmen de Boer, Alessia Amore, and Romano V.A. Orru 

Since the synthesis of urea in 1828 by Friedrich Wohler, synthetic sophistication has been increasing, with many impressive achievements over the past century [1]. Ongoing development of novel synthetic concepts and methods has continued to provide routes to the construction of many complex and challenging synthetic targets. 

Inspired by the mode of action of Nature, numerous groups have reported the multi-step, single operation construction of complex molecules, in which several bonds are formed in one sequence without isolating the intermediates [3-9]. Such processes, which are commonly referred to as tandem reactions, enable ecologically and economically favorable production of a wide range of organic compounds and will be the subject of discussion of the next section. 

Microwaves in Organic Synthesis, Second edition. Edited by A. Loupy Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31452-0 

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Multicomponent Reactions Under Microwave Irradiation Conditions... 

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

Gelens E, De Kanter FJJ, Schmitz RF et al (2006) Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation. Mol Divers 10(1) 17-22 Acke DRJ, Orru RVA, Stevens CV (2006) Continuous synthesis of tri- and tetrasubstituted imidazoles via a multicomponent reaction under microreactor conditions. QSAR Comb Sci 25(5-6) 474-483... 

Partially hydrogenated quinoline cores are also present in some important bioactive compounds. For example, the 4-aza-analogs of Podophyllotoxin, a plant lignan that inhibits microtubule assembly, revealed to be more potent and less toxic anticancer agents. In 2006, Ji s group reported a green multicomponent approach to a new series of these derivatives, consisting of the reaction of either tetronic acid or 1,3-indanedione with various aldehydes and substituted anilines in water under microwave irradiation conditions (Scheme 26) [107]. For this efficient and eco-friendly transformation, the authors proposed a mechanism quite similar to the one that was postulated for the synthesis of tetrahydroquinolines in the precedent section. 

Tu and coworkers [56] synthesized new substituted 2,4-diaminopyridine-3,5-dicarbonitriles 92 under microwave irradiation and solvent-free conditions (Scheme 12.35). The multicomponent domino reaction of 2 mol of malononitrile... 

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