Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• . Importantly, this represents the first example where an isocyanide-based multicomponent reaction has been applied to an isatin-derived ketimine, thus highlighting the promising reactivity of this derivative as a precursor of chiral 3,3-disubstituted 3-aminooxindoles. Biologically active agents containing a 3

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• and macrocyclic peptidomimetics. Keywords: heterocycles; isocyanides; macrocycles; multicomponent reaction; medicinal chemistry; organic synthesis; peptidomimetics; Introduction Peptides and proteins fulfill a key role in many biological and physiological functions of living organisms. Therefore

• substitutions, and macrolactonizations. Even more interestingly, it is possible to perform the cyclization step via a second multicomponent reaction [22] or the MiB (multiple multicomponent macrocyclizations including bifunctional building blocks) protocol developed by Wessjohann et al. (vide infra) [26

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• critical importance, and the transformation of intermediate 4 into the final products 5 was found to work only in DMF, among many investigated solvents. Since the reaction between 4 and 1 is proposed to be catalyzed by acid, we carried out the multicomponent reaction in a selection of solvents (dioxane

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• mechanism, emphasizing the crucial role of manganese is proposed. Keywords: carbonyl compounds; cobalt; manganese; multicomponent reaction; organic bromides; sulfonamides; Introduction (Diarylmethyl)amines constitute an important class of pharmacologically active compounds, displaying e.g. antihistaminic

• thioformamides [28], multistep reactions involving carbonyl compounds [29][30], intramolecular electrophilic arylation of lithiated ureas [31], and Petasis-type multicomponent reaction [32][33][34] have been reported for their preparation. Although these methods propose complementary approaches to the synthesis

• room temperature. To the best of our knowledge, this constitutes the first manganese-mediated multicomponent reaction involving aryl halides as the source for nucleophilic species. Results and Discussion We previously reported that primary amines are not active in a Mannich-like multicomponent reaction

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• nitriles is retained during this reaction [40]. In the present report we describe our efforts to further broaden the substrate scope of this multicomponent reaction and the subsequent cyclizations by employing aromatic dicarboxylic acids. This extension should allow a rapid access to fairly complex

• -methoxy-β-ketoenamides). With these products of a multicomponent reaction we performed cyclizations to rapidly construct symmetrically and unsymmetrically substituted pyridine and pyrimidine derivatives. Hence a very short approach to fairly complex functionalized oligoaromatic systems was established. In

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• a Claisen–Ireland rearrangement to afford an advanced intermediate 27 for the completion of the total synthesis (Scheme 20). 1-Aza-4-borono-1,3-dienes A few years before the description of the tandem process concerning the 3-boronoacrolein, Hall and co-workers realized a multicomponent reaction

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• in methanol. Shifting to trifluoroethanol this side reaction was mostly, but not totally, suppressed. Conclusion In conclusion, we have reported a further example of a synthesis of seven-membered heterocycles by coupling the Ugi multicomponent reaction with an intramolecular Mitsunobu reaction. This

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• has been performed using the sequence of the Ugi multicomponent reaction and Cu(I)-catalyzed click chemistry. The effect of obtained γ-carboline–peptide conjugates on the rat liver mitochondria was evaluated. It was found that all compounds in the concentration of 30 µM did onot induce depolarization

• autooxidation and the t-BHP-induced lipid peroxidation. Keywords: mitochondrial membrane potential; mitochondrial permeability transition; multicomponent; peptides; tetrahydro-γ-carbolines; Ugi multicomponent reaction; Introduction The design and synthesis of new efficient pharmaceutical drugs for the

• catalytic amounts of CsF (Scheme 1). The corresponding protected azidopeptides 5 [14][15] are accessible by the Ugi multicomponent reaction [16][17][18][19] of chiral isocyanoazides 4 [20] with carbonyl compounds, amines and Boc-protected amino acids (Scheme 2). As we showed before, the racemization of the

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• imines with isocyanides is mainly focused on to the well-known Ugi multicomponent reaction (MCR) [1]. This fundamental process features the participation of a carboxylic acid group which attacks the intermediate nitrilium ion thus leading, after the Mumm rearrangement, to α-amidoamides. However, the

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• : benzothiazole; domino reaction; electron-deficient alkyne; multicomponent reaction; pyrrolidinone; Introduction Over fifty years ago, Huisgen firstly described the addition reactions of nitrogen-containing heterocycles to electron-deficient alkynes to form 1,4-dipolar intermediates, which can reacted

• day [28]. Thus we chose to employ a one-pot multicomponent reaction procedure to investigate our reaction. A mixture of dimethyl acetylenedicarboxylate, benzaldehyde, 2-aminobenzothiazole and excess piperidine in ethanol was stirred at room temperature for about twenty minutes and then was heated at

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• chiral spirocyclic SPINOL-phosphoric acids. Keywords: Biginelli-type reaction; chiral phosphoric acid; dihydropyrimidinone; iodine; multicomponent reaction; Introduction The dihydropyrimidinones (DHPMs) have exhibited interesting and multifaceted biological activities, such as antiviral, antitumor

• Biginelli [3][4]. Among them, the Biginelli multicomponent reaction, involving a multicomponent condensation of aldehyde, β-ketoester, and urea, provides an easy access to the preparation of DHPMs, because multicomponent reactions (MCRs) are considered with high facileness, efficiency and economy in organic

• of this multicomponent reaction. Conclusion In conclusion, we have demonstrated the first efficient, molecular iodine-catalyzed three-component synthesis of dihydropyrimidinones starting from simple readily available mono-substituted ureas, alkylaldehydes, and arylaldehydes. A significant progress

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• sequence is atom economic and the application of a multicomponent reaction assures diversity. Keywords: alkynes; gold; indoles; multicomponent; spiroindolines; Ugi; Introduction The importance of nitrogen containing heterocyclic molecules in chemical biology is undisputed. The synthesis of such

• diastereoselective synthesis of spiroindolines. The mild reaction conditions and short synthetic sequence are the merits of this method. The flexibility given by the multicomponent reaction assures the generation of diversity. Experimental General procedure for the synthesis of spiroindolines 6a–q To a screw capped

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• ][62], is a well-studied multicomponent reaction, that provides structures with well-catalogued clinical properties for the treatment of cardiovascular disease, thrombosis and atherogenesis [63][64][65][66]. The 4-component process has been carried out under high temperature conditions in an autoclave

• used for the one-step preparation of pyridines and dihydropyridines using the Bohlmann–Rahtz reaction or Hantzsch multicomponent reaction, respectively. Bohlmann–Rahtz pyridine synthesis under continuous flow processing in the presence of a Brønsted acid catalyst allows Michael addition and

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• Mohammad Piltan Loghman Moradi Golaleh Abasi Seyed Amir Zarei Department of Chemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran Department of Chemistry, University of Kurdistan, Sanandaj, Iran 10.3762/bjoc.9.55 Abstract The catalyst-free multicomponent reaction of 1,2

From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies

• Kevin S. Martin,
• Cristian Soldi,
• Kellan N. Candee,
• Hiromi I. Wettersten,
• Robert H. Weiss and
• Jared T. Shaw

Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31

• step involves the use of a β-amino acid-forming three-component reaction (3CR), the scope of which defines its role in the synthetic strategy. Keywords: β-amino acid; benzimidazole; multicomponent reaction; Introduction Library syntheses and high-throughput screening can often be combined to enable

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• scope of this novel reaction is briefly discussed. Keywords: arylamine; cyclopentanedione; isatin; multicomponent reaction; spiro compound; Introduction The spirooxindole is among the most important class of naturally occurring substances, characterized by highly pronounced biological properties, and

• [3][4][5][6]. Isatin and its derivatives may be the most useful starting materials or precursors in the synthesis of a wide number of spirocyclic oxindoles [7][8]. Due to its simple process, easy operation, efficiency and high atomic economy, the multicomponent reaction based on isatin and its

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• multicomponent reaction affording new tricyclic compounds with a dipyrazolo[1,5-a:4',3'-c]pyridine core. Detailed NMR spectroscopic investigations (1H, 13C and 15N) were undertaken with all obtained compounds. Keywords: cyclization; nitrogen heterocycles; NMR spectroscopy; multicomponent reaction; pyrazole

• to the latter was achieved by a multicomponent reaction (MCR) starting from 5-alkynylpyrazole-4-carbaldehydes. Such MCRs, although being present since the early days of organic chemistry, nowadays attract an increasing interest because of their unmatched synthetic efficiency, which permits the

• conditions, firstly each step of the multicomponent reaction was carried out separately. According to the strategy, pyrazole-4-carbaldehyde 1a was primarily condensed with p-toluenesulfonyl hydrazide affording hydrazide 2a in 97% yield (Scheme 1). Secondly, two steps of the applied strategy were performed at

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• ; heterocycle; microwave-assisted synthesis; multicomponent reaction; ultrasound-assisted synthesis; Introduction Multicomponent reactions (MCRs) [1][2][3][4] involving polyfunctional aminazoles as a key reagent are challenging objectives in the modern chemistry of heterocyclic compounds dealing with the

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• 50918, Jeddah 21533, Kingdom of Saudi Arabia Chemistry Department, Faculty of Science, Kuwait University, PO Box 5969, Safat, 13060 Kuwait 10.3762/bjoc.8.3 Abstract The multicomponent reaction of 5-aminopyrazole derivatives with cyclic 1,3-dicarbonyl compounds and dimethylformamide dimethylacetal

• ., either kinetic or thermodynamic [11][12][13]. It has been reported that the use of microwave or ultrasound irradiation provides an additional parameter for synthetic selectivity [14][15][16][17]. Results and Discussion The multicomponent reaction of 5-aminopyrazoles, dimedone and aromatic aldehydes was

• one proton, which was assigned to the pyrazoloquinazolone C3 proton, and which indicates the lack of involvement of such a proton in the condensation leading to the tricyclic system. Although, it was previously reported [20] that, due to reduced steric hindrance, the multicomponent reaction of 5-amino

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• analogues possess a protease-resistant peptoid scaffold and this might lead to an enhanced activity [19][20]. In this endeavor, all Ugi reactions were initiated by pre-imine formation of 5 and reaction with formaldehyde as the oxo-component, after which the multicomponent reaction was completed by the

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• advantage of this multicomponent reaction is to suppress the isolation of the pure form of the arylalkyne derivatives, which often represents a problem due to their ability to dimerize. This one-pot four-step reaction proceeded well with a series of electron-rich and electron-poor aryl iodide derivatives

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• achieved by conducting a multicomponent reaction for improved atom economy, under microwave heating for fast reaction, and with fluorous solid-phase extractions (F-SPE) for ease of purification. Keywords: Biginelli reaction; dihydropyrimidine; diversity-oriented synthesis; fluorous; Suzuki coupling

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• activity of the new compounds towards single-stranded RNA and double-stranded circular DNA. Keywords: DNA; isocyanide; multicomponent reaction; organocatalysis; peptidomimetic; RNA; Introduction RNA cleavage can serve as a molecular tool for biological research [1], as well as for development of

Multicomponent reactions

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 960–961, doi:10.3762/bjoc.7.107

• and depsi-peptidic to heterocyclic structures; from reactivity-based to property-based concepts. The sympathetic reader, expert or newcomer, will find a tremendous degree of dynamic and exciting new results in this compilation of multicomponent reaction chemistry. As the guest editor of this Thematic