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Microwave-Assisted Synthesis of Heterocycles pp 31–58Cite as

Microwave-Assisted Multicomponent Reactionsfor the Synthesis of Heterocycles

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Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 1))

Abstract

Multicomponent reactions offer convenient procedures for the introduction of many points of structural diversity into heterocyclic compounds prepared in a straightforward manner in a single synthetic step. Combining these features with the extremely fast reaction kinetics of microwave-assisted organic synthesis provides new methods for the rapid and efficient synthesis of heterocyclic libraries suitable for biological evaluation and SAR studies. This review describes recent discoveries in microwave-assisted multicomponent reactions, primarily carried out using modern microwave synthesizers, for the preparation of both simple and fused heterocyclic targets. Advances in our understanding and the application of traditional multicomponent processes, including the Biginelli, Hantzsch and Ugi condensation reactions, for the synthesis of heterocycles are described, as well as a number of newly discovered multicomponent reactions for the preparation of nitrogen-, oxygen- and sulfur-containing, five- and six-membered, partially unsaturated or fully aromatic, heterocyclic rings. Methods for the construction of more complex fused heterocyclic motifs, and the benzo-derivatives of simple heterocycles, are described, with particular emphasis on new combinatorial methodology and the introduction of structural diversity. In many cases, microwave irradiation offers considerable improvements in chemical yield and constitutes a very simple and extremely rapid method to access a diverse range of heterocyclic motifs.

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Abbreviations

DCE:

1,2-dichloroethane

DIPEA:

Diisopropylethylamine

DHP:

Dihydropyridine

DHPM:

Dihydropyrimidine

F-SPE:

Fluorous solid phase extraction

MAOS:

Microwave-assisted organic synthesis

MCR:

Multicomponent reaction

Nap:

2-naphthyl

PEG:

Polyethylene glycol

PS-DMAP:

Polystyrene-bound dimethylaminopyridine

Rf8 :

Perfluorooctyl, C8F17

RT:

Room temperature

SAR:

Structure-activity relationship

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Authors and Affiliations

  1. School of Chemistry, Main Building, Cardiff University, Park Place, CF10 3AT, Cardiff, UK

    Mark C. Bagley & M. Caterina Lubinu

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  1. Mark C. Bagley
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  2. M. Caterina Lubinu
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Correspondence to Mark C. Bagley .

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Erik Van der Eycken C. Oliver Kappe

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Bagley, M.C., Lubinu, M.C. Microwave-Assisted Multicomponent Reactionsfor the Synthesis of Heterocycles. In: Van der Eycken, E., Kappe, C.O. (eds) Microwave-Assisted Synthesis of Heterocycles. Topics in Heterocyclic Chemistry, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_004

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