One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• ; multicomponent reaction; one-pot reaction; spiro[indoline-3,4'-pyridine]; Introduction The spirooxindole system is the core structure of many natural products and pharmaceutically important structures with notable structural complexity and biological activities of great interest [1][2][3][4]. Accordingly, many

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -imidazo[1,2-b]pyrazole; isocyanide; multicomponent reaction; N-heterocycles; Introduction For the relatively rapid design and construction of a diverse, large pharmacophore library, the basic concepts of diversity-oriented synthesis and isocyanide-based multicomponent reactions, such as the Ugi four

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• multicomponent reaction is slightly modified, compared to the described method [33], in order to optimize the yields. The yield of 4-oxazole derivative 1 was 50% whereas the best result found for the 5-oxazole derivative 2 was 22%. The required oxazole-4/5-carbaldehydes (3, 4) [34][35][36] were prepared from

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• economy, wide substrate scope and high yields. Keywords: α-amino amidines; iodine; isocyanide; multicomponent reaction; Ugi reaction; Introduction Amidines are a class of organic compounds exhibiting a variety of biological activity that makes them potential candidates for drug development and discovery

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• assistance [17]. In view of the fact, that the two-step conversion 2→4a,b→5a,b was characterized by only moderate overall yields (59%, resp. 43%) it was considered to merge these two steps into a one-pot multicomponent reaction. The latter type of reaction attracts increasing attention in organic chemistry

• multicomponent reaction following the path 2→9→7. Azine N-oxides of type 7 are estimated to be of particular interest due to the possibility of further functionalization adjacent to the nitrogen atom (position 4), for instance by palladium-catalyzed direct arylation reactions [31]. NMR spectroscopic

• ). In the case of the former (5) the described multicomponent reaction approach is superior compared to the sequential one, whereas the step-by-step synthesis of N-oxides 7 is still characterized by higher overall yields. In addition, in-depth NMR studies with all synthesized compounds were performed

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• . Biochemical properties of the novel nucleoside analogs are also presented (if provided by the authors). Keywords: multicomponent reaction; nucleoside analog; nucleoside antibiotics; nucleoside construction; nucleoside modification; Introduction Chemical modifications of natural ribose or 2'-deoxyribose

• employment of MCRs in the synthesis of nucleoside analogs. The references were selected in accordance with the definition of a MCR given by Ugi et al.: “a multicomponent reaction comprises reactions with more than two starting materials participating in the reaction and, at the same time, the atoms of these

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• (Scheme 1, path C) as a multicomponent reaction (MCR). The utility and importance of MCRs have been recognized by chemists [20][21][22][23]. Several MCRs are now well-established reactions, such as Ugi [24], Passerini [25], Van Leusen [26], Strecker [27], Hantzsch [28], and Biginelli [29][30][31]. However

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