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

• dihydropyridine synthesis; heterocycles; microwave synthesis; multicomponent reactions; pyridine synthesis; Introduction Microwave-assisted synthesis has revolutionized many processes in recent years as a valuable alternative to the use of conductive heating for accelerating transformations in synthetic organic

Creating Complexity

• Donald Craig

Beilstein J. Org. Chem. 2013, 9, 1881–1882, doi:10.3762/bjoc.9.220

• omission of protecting groups or the harnessing of intrinsic reactivity, or the shortening of synthesis sequences by carrying out cascade and multicomponent reactions and chemistry in flow. This Thematic Series brings together a select group of contributors, recognised for their contributions in the areas

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• useful methods because they can provide a shortcut to desired products. Various methods used widely, such as organometallic reactions, cycloaddition reactions and multicomponent reactions, are utilized for multifunctionalization [1][2][3][4][5]. If direct functionalization reactions of inactivated bonds

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

• derivatives have become an efficient method for the synthesis of various spirooxindoles in recent years [9][10]. It is known that the multicomponent reactions of isatins with in situ formed azomethine ylides have become the efficient synthetic procedure for constructing versatile spirooxindole systems [11][12

• ][13][14]. Considering the above reports, and as part of our program aimed at developing new multicomponent reactions for the construction of complex heterocyclic compounds, we wish in this work to report the efficient synthesis of unprecedented cyclopentyl-fused spiro[dihydropyridine-oxindoles] by the

• enol group in each cyclopentane-1,3-dione moiety. Although at present the exact mechanism of this three-component reaction is not very clear, a plausible reaction mechanism for the formation of spiro[dihydropyridine-oxindoles] is presented based on the similar multicomponent reactions of isatins [22

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• complex cascade, tandem and multicomponent reactions. However, the stereochemical outcome of many reactions involving chiral organocatalysts is dependent on the reaction conditions and mainly on the nature of the solvents. Thus, it is highly desirable to develop some new organocatalysts whose catalytic

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

• Fachbereich Chemie, Universität Konstanz, Fach M-720, Universitätsstrasse 10, 78457 Konstanz, Germany Chemistry Faculty, Karazin Kharkiv National University, Svobody sq., 4, 61077 Kharkiv, Ukraine 10.3762/bjoc.8.236 Abstract Multicomponent reactions involving polyfunctional 4-amino-5-carboxamido-1,2,3

• ; 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

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• Organocatalytic reactions are complex multicomponent reactions, and a detailed description of the kinetics of the complete catalytic cycles is not yet possible. We have demonstrated, however, that important information can be obtained by specifically synthesizing relevant intermediates and studying the kinetics

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• -lactam to γ-lactam ring expansions [29][30], aziridine ring openings followed by cyclization with enolates [31], palladium-catalyzed cyclizations [32], cycloadditions [33], multicomponent reactions [34], and even NHC catalysis [35][36]. Nevertheless, the methodology developed by Rovis indisputably

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

• a wide range of biological activities [3][4]. Multicomponent reactions (MCR) occupy an interesting position in organic synthesis because of their atom economy, simple procedures and convergent character [5][6][7]. An unresolved issue in multicomponent reactions is whether their selectivity is chemo

• tricyclic reaction products, no general basis on which to determine the preferred tautomeric form of the final product has been established. In continuation of our studies in which we performed multicomponent reactions using controlled microwave heating [22][23][24], we report herein the results of our

• investigation concerning the regioselectivity in multicomponent reactions of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal (DMFDMA) under controlled microwave heating. We began this study by treating 5-amino-3-methylpyrazole (1a) and dimedone (2a) with DMFDMA (3) in DMF under

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

• by acylation with (S)-2-methylbutanoic acid (c) [15] (Figure 1). Based on this flexible route, we also envisioned the synthesis of derivatives utilizing post-cyclization transformations by multicomponent reactions. This diversity-driven approach benefits from the fact that the heterocyclic moiety may

Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• title compounds. This novel pseudo five-component synthesis starting from iodo(hetero)arenes is particularly suitable as a direct access to well-defined thiophene oligomers, which are of peculiar interest in materials science. Keywords: C–C coupling; copper; multicomponent reactions; palladium

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

• -component synthesis has emerged as an important synthetic methodology to gain access to nitrogen-containing structures. The latest developments in this area are discussed in this review. Keywords: amines; multicomponent reactions; palladium; Introduction Nitrogen-containing structures are present in

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• . Keywords: heterocycles; metal free synthesis; multicomponent coupling; piperidine; recyclable catalyst; Introduction Multicomponent reactions [1][2][3][4][5], involving the one-pot reaction of three or more components to produce valuable compounds, have been recognized as one of the important tools to

• achieve highly efficient, atom economic and energy-saving organic syntheses. These multicomponent reactions (MCRs) offer many advantages over conventional multistep syntheses, such as lower costs, shorter reaction times, high atom economy, avoidance of expensive purification processes [6][7], and the fact

• that it is more environmentally friendly [4][5][8][9]. Among the various known multicomponent reactions, the MCRs that involve 1,3-dicarbonyl compounds, aldehydes, and nucleophilic compounds have received particular interest in recent years owing to their potential to provide different condensation

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• ; isocyanide; pyrazolidinone; Introduction In the last twenty years, the Ugi reaction coupled with its various post-condensations towards heterocyclic libraries has established the success of isocyanide-based multicomponent reactions [1][2][3][4][5][6][7]. Chemists in both academia and industry have taken

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• : amino acids; chelated enolates; epoxides; Passerini reactions; Ugi reactions; Introduction Multicomponent reactions (MCR) are a very popular and powerful tool in modern organic synthesis [1][2][3][4]. Besides a wide range of heterocycle syntheses [5] and catalytic cross coupling reactions [6], the

• reactions together have made the IMCR highly popular in combinatorial chemistry [7][8]. Our group has been involved in amino acid and peptide synthesis for nearly two decades [12][13], and multicomponent reactions are known to play a dominant role [14][15]. In particular, the Ugi reaction has so far been

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

• synthesis of heterocyclic scaffolds. The intermediates obtained from the Biginelli reaction were used for post-condensation modifications to afford biaryl-substituted dihydropyrimidinone, dihydropyrimidine, and thiazolopyrimidine compounds. A set of reaction and separation techniques such as multicomponent

• reactions, microwave heating, and F-SPE was employed to increase the synthetic efficiency. The fluorous sulfonyl group not only served as a phase tag for F-SPE separation, but also as a cleavable linker for the Suzuki coupling reactions. Experimental Typical Biginelli reaction procedure: Synthesis of 5

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• ; multicomponent reactions; ynones; Introduction Diversity-oriented synthesis has become an important field in organic chemistry, initiated by the increasing demand for new scaffolds for pharmaceuticals and biologically active compounds over the past decades [1][2][3]. Herein, multicomponent reactions adopt a

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

• especially important because multicomponent reactions (MCR) could be adapted to a high throughput synthesis of libraries of compounds. It is known that isocyanide-based MCR are very efficient for synthesis of peptides and peptide molecules [19][20][21][22][23][24]. We proposed that the desired compounds 5

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• building blocks have been used in the Ugi four-component reaction to construct a fluorinated compound library [22][23][24][25]. Our group has always been interested in developing efficient methods for the preparation of difluoromethyl-containing compounds through multicomponent reactions [26][27][28][29

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

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

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• steps are conducted concomitantly to render the procedure as practical and straightforward as possible. Therefore, the whole experimental protocol takes less than two hours. Keywords: acyliminium; amides; carbamates; multicomponent reactions; organozinc reagents; Introduction Diarylmethylamines

• group has been involved in various projects pertaining to the development of multicomponent reactions (MCRs) involving organometallic reagents, in particular organozinc reagents, due to their ability to react in very mild conditions and generally preserve most common functional groups. Moreover, used in

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• reactions and practical protocols. Keywords: manganese dioxide; multicomponent reactions; oxidation; Povarov; quinolines; tetrahydroquinolines; Introduction Heterocycles are ubiquitous scaffolds in pharmaceuticals, natural products and biologically active compounds. Quinoline systems in particular

• ]. Multistep sequences are widespread in the literature, but even in these cases the preparation of some substitution patterns and functional group combinations is particularly difficult. The recent introduction of multicomponent reactions (MCRs) into this field has brought interesting features typical of the

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• membered cyclic imines. It allows the diversity-oriented synthesis of various tetrahydro[f][1,4]benzoxazepines. Keywords: benzoxazepines; cyclic imines; long range stereoinduction; multicomponent reactions; Ugi reaction; Introduction The Ugi reaction is probably the most renowned and widely used

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• : allenes; enantiopure pyridines; ketoenamides; multicomponent reactions; nonaflates; Introduction The pyridine core is ubiquitous in pharmacologically active agents, agrochemicals and natural products [1][2][3][4][5]. The HMG-CoA reductase inhibitors Glenvastatin and Cerivastatin are exemplarily mentioned

• enantiopurity [40]. Chiral carboxylic acids are readily available and their use would allow for a rapid access to pyridines with side chains bearing stereogenic centers. In recent years we studied intensively the multicomponent reactions of lithiated alkoxyallenes with nitriles and carboxylic acids and could

Multicomponent reactions

• Thomas J. J. Müller

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

• highly diverse. Additionally, the criterion of selectivity has to be matched with increasing significance economical and ecological aspects. In particular multicomponent reactions (MCR) [3] are masterpieces of synthetic efficiency and reaction design. These one-pot processes consist of concatenations of

• elementary organic reactions under similar conditions. Most interestingly, multicomponent reactions have accompanied the field of organic chemistry since the early days, particularly in heterocyclic chemistry, but have not been recognized as a fundamental principle until Ugi's groundbreaking extension of the

• lead structures of active agents, catalysts and even novel molecule-based materials. This Thematic Series on multicomponent reactions represents a snapshot of a highly dynamic field and spans a broad range, from recent advances in isonitrile-based MCR to transition metal catalysis in MCR; from peptidic

Surfactant catalyzed convenient and greener synthesis of tetrahydrobenzo[a]xanthene-11-ones at ambient temperature

• Pravin V. Shinde,
• Amol H. Kategaonkar,
• Bapurao B. Shingate and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2011, 7, 53–58, doi:10.3762/bjoc.7.9

• forming surfactants as catalysts in water is widespread and has been studied for a number of different synthetic transformations/ multicomponent reactions in water [4]. Multicomponent reactions (MCRs) have emerged as an extremely powerful tool in combinatorial chemistry and drug discovery, since they