Review

. 2009 Dec 1;14(12):4936-72.

doi: 10.3390/molecules14124936.

Microwave multicomponent synthesis

Helmut M Hügel¹

Affiliations

PMID: 20032870
PMCID: PMC6254856
DOI: 10.3390/molecules14124936

Review

Microwave multicomponent synthesis

Helmut M Hügel. Molecules. 2009.

. 2009 Dec 1;14(12):4936-72.

doi: 10.3390/molecules14124936.

Author

Helmut M Hügel¹

Affiliation

¹ School of Applied Sciences, RMIT University, GPO Box 2476V Melbourne, Victoria 3001, Australia. helmut.hugel@rmit.edu.au

PMID: 20032870
PMCID: PMC6254856
DOI: 10.3390/molecules14124936

Abstract

In the manner that very important research is often performed by multidisciplinary research teams, the applications of multicomponent reactions involving the combination of multiple starting materials with different functional groups leading to the higher efficiency and environmentally friendly construction of multifunctional/complex target molecules is growing in importance. This review will explore the advances and advantages in microwave multicomponent synthesis (MMS) that have been achieved over the last five years.

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Figures

**Scheme 1**
Optimized Biginelli reaction conditions for dihydropyrimidine synthesis.

**Scheme 2**
Optimized Biginelli reaction conditions for bromophenyl-substituted DHPM synthesis.

**Scheme 3**
Bronsted acid catalyzed Biginelli DHPM synthesis.

**Scheme 4**
Biginelli reaction for synthesis of 2-amino-4-arylpyrimidines.

**Scheme 5**
Biginelli reaction to 2-thioxopyrimidines and derivatives.

**Scheme 6**
The Biginelli reaction route to 2-amino-DHPMs.

**Scheme 7**
Generation of 5-aroyl-3,4-dihydropyrimidin-2-one library from Biginelli and Liebeskind-Srogl coupling reactions.

**Scheme 8**
The utilization of IL-PEG technology for the Biginelli, Hantzsch reactions.

**Scheme 9**
MW-tuning chemo- and regio-selectivity of three-component condensation products.

**Scheme 10**
Formation of pyrazoloquinazolinone 5 and pyrazoquinolizinone 6 by three-component-base condensation reactions.

**Scheme 11**
Optimized Biginelli-MMS of Monastrol.

**Scheme 12**
The asymmetric Biginelli-MMS.

**Scheme 13**
The Ugi reaction: The effects of MW, solvents, bifunctional substrates.

**Scheme 14**
Ugi MMS to racemic 1,4-benzodiazepin-3-ones A or B.

**Scheme 15**
Sequential Ugi plus Suzuki coupling to form 2,3,6-trisubstituted imidazo(1,2-a)pyridines.

**Scheme 16**
Ugi-MMS with intramolecular O-alkylation furnishing substituted benzoxazines.

**Scheme 17**
Ugi-MMS with tandem deprotection/intramolecular N-cyclizations to triazadibenzoazulenones.

**Scheme 18**
The UDC-MMS strategy leading to diketopiperazines and 1,4-benzodiazepine-2,5-diones.

**Scheme 19**
MMS-MACOS provided a small library of 2-amino furans.

**Scheme 20**
Production of pyrazoloquinolinones by Hantzsch-MMS using MACOS in DMSO.

**Scheme 21**
Hantzsch-MMS of polyhydroquinolines catalyzed by Ni-nanoparticles.

**Scheme 22**
MMS of indolyl-pyridine derivatives.

**Scheme 23**
MMS of polycyclic-fused isoxazolpyridines in water.

**Scheme 24**
MMS of fuoro- and indeno-pyridopyrimidines in water.

**Scheme 25**
Hantzsch-MMS of 4-(C-galactosylmethyl)-2-(alaninyl)pyridine and 2-(C-galactosylmethyl)-4-(alaninyl)pyridine derivatives.

**Scheme 26**
MMS of functionalized hexa-substituted 1,4-dihydropyridines.

**Scheme 27**
Conventional heating of four-component reaction providing mixtures of hexa-substituted 1,4-dihydropyridines.

**Scheme 28**
MMS of naphtha[2,3-f]quinoline derivatives.

**Scheme 29**
MMS of polysubstituted imidazo[1,2-a]-quinazolines, pyrimido[1,2-a]-quinolines, quinolino[1,2-a]-quinazolines.

**Scheme 30**
The three-component—MW synthesis of Glyantrypine, Fumiquinazoline F and Fiscalin B.

**Scheme 31**
Three-component—MW synthesis of Circumdatin E analogues.

**Scheme 32**
Three-component - MW synthesis of Isaindigotone.

**Scheme 33**
Summary of MMS of the Quinazolin-4-one scaffold.

**Scheme 34**
Utilization of MMS in the synthesis of Steganacin aza-analogues.

**Scheme 35**
MMS of multiring heterocycles.

**Scheme 36**
Alkaloid synthesis *via* MMS/RCM/Heck reactions.

**Scheme 37**
The parallel MMS of imidazothiazol-3-one and imidazothiazin-4-one products.

**Scheme 38**
The chemoselective MMS of N-substituted 2-aminopyridines and substituted 2,6-dicyanoanilines.

**Scheme 39**
MMS of spiroimidazolinones by one-pot sequential and domino reactions.

**Scheme 40**
The synthesis of Irbesartan by a one-pot two-step reaction sequence.

**Scheme 41**
Optimized MMS of imidazoles.

**Scheme 42**
MMS of piperazinedione-fused tricyclic compounds.

**Scheme 43**
MMS products from aldehydes, phenylpyruvic acid and aminoazoles.

**Scheme 44**
MMS of the 4-oxotetrahydro-β-carboline scaffold.

**Scheme 45**
MMS of a substituted 2-aminochromene.

**Scheme 46**
MMS of 2-aminochromenes using Mg/Al catalysis.

**Scheme 47**
Zinc chloride catalyzed MMS of 2-amino-3,5-dicarbonitrile-6-thio-pyridines.

**Scheme 48**
MMS of coumarin substituted pyridine derivatives.

**Scheme 49**
MMS protocols to spirooxindoles.

**Scheme 50**
MMS influence by solvent and substituent effects.

**Scheme 51**
Solvent-selective MMS of 6-hydroxy-3-pyrimidin-5-yl propanoic acid, 6-hydroxy-3-pyrimidin-5-yl propanamide and spiro [5,5]undecane-1,5,9-triones.

**Scheme 52**
MMS of tricyclic thiochromeno[2,3-b]pyridine derivatives.

**Scheme 53**
The synthesis of pyrano-1,4-benzoquinone adducts.

**Scheme 54**
The MMS of heteropolycyclic compounds.

**Scheme 56**
MMS approach to furanose-pyranose 1,3-C-C-linked-disaccharides.

**Scheme 57**
MMS of N-1, C-6-disubstituted 3,5-dichloro-2(1H)-pyrazinones.

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References

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Microwave multicomponent synthesis

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Microwave multicomponent synthesis

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