Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• considered as the analogues of both 3,3’-spirooxindole and 2-aminoimidazole marine sponge alkaloids. Keywords: 2-amino-4-arylimidazole; (2-amino-4-arylimidazolyl)propanoic acid; isatin; Meldrum’s acid; multicomponent reactions; pyrrolo[1,2-c]imidazole; 3,3’-spirooxindoles; Introduction Heterocyclic

• that mimic the core structure of marine alkaloids due to the presence of several reaction centres, which allow their further chemical modification. In the present work we disclose our results on the multicomponent reactions between 2-amino-4-arylimidazoles, aromatic aldehydes or isatins and cyclic or

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• Angelica de Fatima S. Barreto Carlos Kleber Z. Andrade Universidade de Brasília, Instituto de Química, Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), 70910-970 Brasília-DF, Brazil 10.3762/bjoc.15.88 Abstract Isocyanide-based multicomponent reactions are a versatile tool in the

• synthesis of heterocycles. This review describes recently developed approaches based on the combination of consecutive or repetitive isocyanide-based multicomponent reactions for the synthesis of structurally diverse heterocycles. These strategies have also allowed the synthesis of a plethora of

• macroheterocycles in a reduced number of steps. Keywords: consecutive/repetitive multicomponent reactions; isocyanide; isocyanide-based multicomponent reactions; (macro)heterocycles; Passerini reaction; Ugi reaction; Introduction Isocyanide (isonitrile) chemistry was first described by Lieke in 1859 [1] and forms

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• new fused heterocyclic backbones has always been a major challenge in the field of organic synthesis [1][2][3]. Multicomponent reactions (MCRs) and domino reactions are known as efficient synthetic approaches for the synthesis of complex molecules [4][5][6]. Domino reactions have been defined by

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• molecules using multicomponent reactions (MCRs). MCRs transform three or more starting materials into a single product in an atom- and step-economical way in diversity- and target-oriented syntheses in modern organic synthesis. In addition, MCRs are characterized by high yields, time efficiency, low waste

• aliphatic amines and ordinary isocyanides with excellent yields [24]. In 2003, Mironov et al. reported the Ugi reaction of levulinic acid, isocyanides and primary amines in aqueous media with high yields [25]. In addition, Banfi et al. have shown that by using levulinic acid in multicomponent reactions and

• post-multicomponent reactions, diversities of bicyclic drug-like heterocyclic compounds can be obtained [26]. Results and Discussion In continuation of our interest on the synthesis of novel pseudo-peptides [27][28][29] via multicomponent reactions, herein we investigate the Ugi-4C-3CR of levulinic

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• -inflammatory [5], and antidiabetic agents [6]. The numerous known methods for the preparation of these compounds are generally based on multicomponent reactions of an aromatic aldehyde, a β-keto ester, a hydrazine and malononitrile [7]. In a similar reaction using a pyridinium ylide instead of malononitrile

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• reactions are possible. Keywords: allenes; condensations; multicomponent reactions; oxazoles; pyrimidines; quinoxalines; Introduction Multicomponent reactions are known to create unique product skeletons in an atom economic, efficient and time saving fashion. In many cases, compounds bearing functional

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• /HPF6 and studied by NMR and by DFT and GIAO-DFT. Keywords: model heteroarylmethylium salts; multicomponent; one-pot catalyst-free assembly; pharmacophoric triads; three-component synthesis; tris(heteroaryl)methanes; Yonemitsu-type reaction; Introduction During the last few decades multicomponent

• reactions (MCRs) have gained importance as a suitable strategy for the synthesis of diverse synthetic and naturally occurring compounds of biological and practical interest. This approach offers several advantages including simplicity, high reaction rates, and high bond-forming efficiency [1][2][3][4][5

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• of Bologna, Via Belmeloro, 6, 40126, Bologna, Italy 10.3762/bjoc.15.46 Abstract Multiple multicomponent reactions reach an unparalleled level of connectivity, leading to highly complex adducts. Usually, only one type of transformation involving the same set of reactants takes place. However, in some

• reactions; reaction discovery; selectivity; Introduction Organic synthesis has become fundamental in science and technology, affecting many aspects of our lives. Therefore, there is a big need for the optimized preparation of a variety of compounds [1][2][3]. In this context, multicomponent reactions (MCRs

• multicomponent reactions (MMCRs) display impressive power regarding connectivity and bond-forming efficiency and can be considered as ideal synthetic processes in many aspects [5]. These features may be maximized if the controlled incorporation of distinct reactant units, belonging to the same class, along the

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• ][12]. For this reason a great effort is ongoing to utilize multicomponent reactions for the synthesis of macrocycles [8][13][14][15][16][17][18][19][20][21][22][23][24][25]. The p53 protein is a well-studied protein which has a leading role in protecting our organism from cancer. It was found that

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• role as precursors in the synthesis of bioactive compounds [13][26][27], substrates for multicomponent reactions [28], and lately, have successfully been applied in polymer photodecoration [29][30]. They can easily be reduced into chiral hydroxy derivatives [31] and properly oxidised at sulfur to

• generate the corresponding chiral sulfoxides or sulfone derivatives [32]. Multicomponent reactions (MCRs), in which three or more reagents react giving rise to generally complex molecules in one-pot, have arisen as a powerful tool to connect fragments in a simple manner, avoiding cost and time-consuming

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• given to domino reactions with an oxidation step, revealing possibilities for shifting the equilibrium by making products more stable or in situ generating reactive intermediates [2][3][4][5][6][7][8][9][10][11][12][13]. In its turn, multicomponent reactions (MCRs), usually occurring as domino processes

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• received less attention. For instance, the multicomponent reactions of aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitriles and 5-aminopyrazol or naphthylamine afforded indole substituted fused pyridine derivatives [56]. 2-Indole substituted pyridine derivatives have also been prepared through AlCl3-induced C

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• ]), transition metal salts-catalyzed [4 + 2] [13][14][15][16][17][18], [2 + 2 + 2] [19][20][21][22][23][24][25][26], and [3 + 3] cyclization reactions [27], multicomponent reactions [28][29][30][31][32][33], and direct C–H functionalizations on the pyridine rings [34][35][36]. Particularly, the fascinating

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• liquids 18 or 19 were again applied for next runs. Shirini et al. have reported a series of procedures for the synthesis of sulfonated materials and their applications for one-pot multicomponent reactions. This research group has reported a new route for the preparation of bi-SO3H ionic liquids based on

• multicomponent reactions and some of them were mentioned below. Moosavi-Zare et al. immobilized 1,4-diazabicyclo[2.2.2] octanesulfonic acid chloride on SiO2 as a nanostructured heterogeneous catalyst. The silica-bonded 1,4-diazabicyclo[2.2.2]octanesulfonic acid chloride catalyst 71 was prepared in some steps as

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• nitroacetate and organic azides, in which the synthesis of both triazolocoumarin regioisomers was accomplished [33]. Interestingly, the expected regioisomer was not observed in the case of the in situ formed 3-nitrocoumarins. Hence, in our continued exploration towards novel multicomponent reactions for the

• yielding 13 in 51% yield. Since aldehydes are interesting and versatile functional moieties for further derivatization, e.g., used in the synthesis of heterocyclic scaffolds [33][34][50], several multicomponent reactions [40][51][52][53], etc., we wished to convert dimethyl acetal 5j into aldehyde appended

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• ) reaction [11][12], and rearrangement of spiro-ketones, nucleophilic substitutions of alkenes, and photochemical addition reactions. Multicomponent reactions (MCRs) are also used for the synthesis of hetero-propellanes [13][14]. Recently, heterocyclic propellanes have been reviewed [15][16]. Our group also

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• accessed by designing sequential organic transformations incorporating multicomponent reactions [1][2] combined with secondary transformations [3][4][5][6][7][8][9][10][11]. Over the past decade, several groups of chemists interested in synthetic chemistry have efficiently utilized the strategy of linking

• multicomponent reactions with intramolecular azide–alkyne cycloaddition (IAAC) for the generation of triazole-fused heterocycles [12][13][14][15][16][17][18][19][20][21][22][23]. In this report we disclose our results on the development of a sequential synthetic approach involving Ugi 4-component reaction (4-CR

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazoles 16, cyclic β-diketones 58 and heteroaryl aldehydes 47 (Scheme 17). The reaction under conventional heating in DMF provided best results with high yields of the corresponding pyrazolo[3,4-b]pyridines 74. The multicomponent reactions of 5-(4-substituted-benzylamino)pyrazoles 75, cyclic-β-diketones

• time for the completion of reaction. El-borai et al. [71] accomplished the synthesis of pyrazolo[3,4-b]pyridine derivatives 88 in which the multicomponent reactions of β-ketonitriles 15, 5-aminopyrazole 16 and anisaldehyde (47) were carried out in acetic acid under conventional heating and microwave

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• Angelica de Fatima S. Barreto Veronica Alves dos Santos Carlos Kleber Z. Andrade Laboratório de Química Metodológica e Orgânica Sintética, Instituto de Química, Universidade de Brasília, 70910-970, Brasília-DF, Brazil 10.3762/bjoc.13.256 Abstract Isocyanide-based multicomponent reactions (IMCRs

• . The products synthesized herein contain functional groups within their structures that can be easily modified to obtain new acylhydrazino 1,5-disubstituted tetrazoles. Keywords: acylhydrazines; consecutive Ugi reactions; 1,5-disubstituted tetrazoles; isocyanide-based multicomponent reactions (IMCRs

• tetrazoles are intermolecular cycloaddition reactions and isocyanide-based multicomponent reactions (IMCRs). Indeed, the Ugi-multicomponent reaction using TMSN3 (trimethylsilyl azide) as acid component, originally reported by Ugi in 1961 [10], is one of the best and most general methods for the synthesis of

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• ] where fundamental organic reactions are combined in one-pot sequences [25][26][27][28][29]. Multicomponent reactions (MCR) take advantage of creating and transforming reactive functionalities in the same reaction vessel without intermediary work-up [30]. Syntheses of functional chromophores by MCR [31

• , sensing and display applications [41]. 4-Phenylnaphtho[2,3-c]furan-1,3-diones can well serve as reactive intermediates in multicomponent reactions, e.g., for synthesizing the corresponding imides. A particularly intriguing access to 4-phenylnaphtho[2,3-c]furan-1,3-diones is the intramolecular [4 + 2

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• achieved by a different approach involving the homodimerization of 1-allyl- or 1-homoallylpyrroles by application of cross-metathesis chemistry. Keywords: diversity-oriented synthesis; mechanochemistry; multicomponent reactions; pyrroles; solvent-free synthesis; Introduction Symmetrical molecules formed

• operations leading to the buildup of the heterocyclic frameworks could be performed using multicomponent reactions. However, the simultaneous construction of two heterocycles in a single operation by means of such reactions has very little precedent in the literature and has never been achieved under

• exploration of heterocyclic chemical space. Such compounds were readily accessible in a single operation via the construction of their pyrrole fragments by means of mechanochemical multicomponent reactions that were performed starting from very simple starting materials and catalysts. Related compounds having

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted. Keywords: ball-milling; green chemistry; mechanochemistry; solid-phase synthesis; solvent-free synthesis

• bond formation reactions, multicomponent reactions, heterocyclic ring synthesis, synthesis of organometallic complexes and their catalytic applications, and so on. Review Mechanochemical organic synthesis Famous philosopher Aristotle’s statement “No Coopora nisi Fluida” means ‘no reaction is possible

• also observed that an oven-dried catalyst worked effectively to give 99% of product with 99% ee up to few cycles. Heterocycle synthesis Multicomponent reactions [135], cyclo-condensations and cascaded transformations are common strategies to make heterocyclic ring [113] systems like pyrroles, pyrans

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• , 1,4-dihydropyridines as calcium channel blockers, such as nifedipine and nicardipine, are found as effective chemotherapeutic medicines and antihypertensive agents [17]. Hence to attend their biological usefulness diverse synthetic processes are reported to access these molecules [18]. Multicomponent

• reactions are one of the key synthetic strategies that are applied to generate various nitrogen heterocycles and subsequent aromatization of these heterocycles afforded the corresponding heteroaromatic derivatives [19]. The aromatization of nitrogen heterocycles is facilitated mainly by dehydrogenation of

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• , when 2-vinylbenzoic acid derivatives were employed as reagents, isobenzofuranones were obtained together with unprecedented benzo[e][1,3]oxazepin-1(5H)-ones, with the latter derived from incorporation of the solvent (acetonitrile). Keywords: flow chemistry; heterocycles; multicomponent reactions

• ; photocatalysis; photo-Meerwein arylation–addition; Introduction Photoinduced multicomponent reactions are currently receiving remarkable attention [1]. Indeed, the possibility to obtain multiple-bond forming reactions under clean and mild conditions is nowadays one of the main targets of green chemistry

• , deriving from the corresponding radical, undergoes a nucleophilic attack by the nitrile, generating nitrilium ion B first, and subsequently evolves to the amide 1, according to a Ritter-type reaction. Based on our experience on multicomponent reactions, we postulated that intermediate A could be

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• HPA and an imine component which has been postulated but never obtained in similar reactions. Keywords: Castagnoli–Cushman reaction; diastereoselectivity; homophthalic anhydride; indolenines; lactam synthesis; multicomponent reactions; Introduction The reaction of imines (prepared in a separate step