Heterocycles multi-component reactions

Multi-component Reactions (lmidazo[l,2-a]annulated N-heterocycles -Ugi reaction)... 

Chebanov VA, Sakhno YI, Saraev VE, Muravyova EA, Andrushchenko AY, Desenko SM (2009) Multicomponent heterocyclizations control of chemo- and regioselectivity. Fourth international conference multi-component reactions and related chemistry , Ekaterinburg, Russia, 1-3... 

Keywords 1,3-Dicarbonyls, Biginelh reaction, Hantzsch reaction, Heterocyclic chemistry, Knoevenagel condensation, Mannich reaction, Michael addition, Multi-component reactions... 

Ugi, I., Domling, A. and Werner, B., Since 1995 the new chemistry of multi-component reactions and their libraries, including their heterocyclic chemistry, J. Heterocyd. Chem., 2000,37, 647. 

While the early examples of this cyclocondensation process typically involved a / -ketoester, aromatic aldehyde and urea, the scope of this heterocycle synthesis has now been extended considerably by variation of all three building blocks, allowing access to a large number of multifunctionalized pyrimidine derivatives. For this particular heterocyclic scaffold the acronym DHPM has been adopted in the literature and is also used throughout this chapter. Owing to the importance of multi-component reactions in combinatorial chemistry there has been renewed interest in the Biginelli reaction, and the number of publications and patents describing... 

The first chiral NHCs of this type were developed by Herrmann and En-ders in 1996. Herrmann s group [6] synthesized a symmetric imidazolium salt 1 (as carbene precursor), starting from an enantiopure chiral amine which was readily converted to the heterocycle using a multi-component reaction previously developed by Arduengo [7]. After coordination to a rhodium(I) complex precursor (Scheme 1), this ligand was tested in the hydrosilylation of acetophenone. 

Pyrrole syntheses have been organized systematically into intramolecular and intermolecular approaches as well as by the location of the new bonds that describe the pyrrole ring forming step (two examples are illustrated below). Multi-component reactions appear at the end of the section on intermolecular approaches. The final section includes pyrrole syntheses that arise from transformations of other heterocycles. 

In an exploration of multi-component reactions for the synthesis of a diverse array of heterocyclic scaffolds Martin et al. demonstrated a cascade reaction involving the imine, formed from the condensation of 2-azidobenzaldehyde 97 with propargylamine, acetyl chloride and ketene acetal 98 to furnish the triazolo-fused benzodiazepine 99 via an intramolecular [3+2] cycloaddition <07OL4223>. 

Zhu SL, Ji SJ, Zhao K et al (2008) Multi-component reactions for the synthesis of new 30-indolyl substituted heterocycles under microwave irradiation. Tetrahedron Lett 49 2578-2582... 

Shi F, Yan S, Zhou D et al (2009) A facile and efficient synthesis of novel pyrimido[5, 4-b] [4, 7]-phenanthroline-9, 11(7H, 8H, lOH, 12Ff)-dione derivatives via microwave-assisted multi-component reactions. J Heterocycl Chem 46 563-566... 

Bremner WS, Organ MG (2007) Multi-component reactions to form heterocycles by micro-wave-assisted continuous flow organic synthesis. J Comb Chem 9 14—16... 

Wang X-H, Hao W-J, Tu S-J et al (2009) Microwave-assisted multi-component reaction for the synthesis of new and significative bisfunctional compounds containing two furo[3, 4-b] quinoline and acridinedione skeletons. J Heterocycl Chem 46 742-747... 

Zhuang Q, Zhou D, Tu S et al (2008) A highly efficient microwave-assisted synthesis of chromeno[3, 4-b][4, 7]phenanthroline derivatives through multi-component reactions in water. J Heterocycl Chem 45 831-835... 

In addition to isocyanide-based MCRs, a wealth of highly functionalized heterocycles can be obtained from 1,3-dicarbonyl, cyanomalonate and malononitrile based MCRs [19]. These easily accessible starting materials participate in a variety of multi-component reactions and have found numerous applications in drug discovery. 

Solution-phase multicomponent methodology for the synthesis of heterocyclic compounds, (non-catalytic syntheses, catalysis with acids and metals, multi-component reactions including cycloaddition are reviewed) 03S1471. 

Since 1995 the new chemistry of multi-component reactions and their libraries including their heterocyclic chemistry 00JHC647. 

A straightforward synthesis of fused dihydrotriazolo[l,5-Q ]pyrazinones and triazolobenzodiazepines by sequential Ugi/alkyne-azide cycloaddition reactions was recently demonstrated by Djuric et al. [55]. The couphng of the Ugi multi-component reaction with the intramolecular alkyne-azide cycloaddition provides access to highly functionaUzed heterocyclic ring systems in just two steps. 

Synthesis of furo-, pyrrolo-, and thieno-fused heterocycles by multi-component reactions 13COS425. 

B. Groenendaal, E. Ruijter, R. V. A. Orru, Chem. Commun. 2008, 5474-5489. 1-Azadienes in cycloaddition and multi-component reactions towards A -heterocycles. 

Keywords Alkyl halides, alkynes, sodium azide, CU2O, methanol, room temperature, multi-component reaction, click synthesis, heterocycles, substituted 5-alkynyl 1,2,3-triazoles... 

In addition to simple enantioselective two-component tandem multi-organocatalysed reactions, several groups have recently reported multi-component reactions based on the enantioselective sequential multiorganocatalysis concept. For example, Cordova et al. disclosed in 2011 a highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine catalysis and iV-heterocyclic carbene catalysis, which allowed the synthesis of a range of chiral N-tert-butox-ycarbonyl and N-carbobenzyloxy-protected (3-amino acid esters to be... 

The saturated imidazolinium salts of type 11 (Scheme 1.7) can be obtained by alkylation of dihydroimidazole or by the cyclization reactions between A,A -dialkyl-a,p-ethyldiamines with orthoesters (Scheme 1.7a). A multi-component reaction leading to unsymmetrical derivatives of type 11, which is particularly interesting for the synthesis of imidazolinium salts with substituents at the C4 and C5 positions of the heterocycle, was reported by Orru... 

D.Q. SW, S.N. Ni, F. Yang, S.J. Ji, An efficient and green synthesis of 3,3 -benzylidenebis (4-hydroxy-6-methylpyridin-2(lH)-one) derivatives through multi-component reaction in ionic liquid, J. Heterocycl. Chem. 45 (2008) 1275-1280. 

Thus, it is clear that in the case of 3-amino-1,2,4-triazole and 5-aminotetra-zole, reactions with arylidenepyruvic acids and their synthetic precursors lead to identical reaction products [199, 201], while applying sequential or multi-component procedures for interaction with 3-substituted 5-aminopyrazoles allows for the isolation of heterocycles of different structures [202]. However, it is interesting to note that, according to publication [202], reactions of 5-amino-7V-arylpyrazolo-4-carboxamides 213 with arylidenepyruvic acids 236 or with pyruvic acid 239 and aldehydes 240 also yielded identical reaction products—pyrimidine heterocycles 255 (Scheme 3.70). 

Heterocyclic chemistry has been a major beneficiary of MW-expedited solvent-lfee chemistry utilizing mineral supported reagents. It has been exploited for parallel synthesis, a strategy that is adaptable for multicomponent reactions, such as Ugi " and Biginelli reactions " , for rapid assembly of a library of compoimds. A representative multi-component condensation reaction to create a small-molecule library of imidazo[l,2-a]pyridines, imidazo[l,2-a] pyrazines, and imidazo[l,2-a]pyrimidines is depicted in Scheme 3. 

Transition-metal catalyzed multi-component carbocyclization and related reactions with participation of heterocycles 99YGK912. 

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