One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• reported a novel multicomponent reaction for the synthesis of S-trifluoromethyl dithiocarbamates from secondary amines, CS2 and Togni's reagent in moderate to good yields. Under similar conditions, a primary amine afforded the corresponding isothiocyanate in excellent yield. The presence of dithiocarbamate

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

• -emitting diodes (OLEDs) [2][3][4][5]. As a consequence efficient and efficacious syntheses of fluorescent molecules can be most advantageously addressed by diversity-oriented syntheses [6][7][8], namely by multicomponent [9][10][11][12][13][14][15][16][17][18][19][20][21] and domino reactions [22][23][24

• ] 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

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• conjugation. The electronic interaction between the covalently connected chromophore unit leads to important changes in the absorption spectra and so these dimers are expected to serve as attractive building blocks for the construction of multicomponent photoinduced electron transfer supramolecular systems

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

• -donating and -withdrawing substitutions on benzaldehydes or in benzoic acids have worked well under the mechano-chemical conditions [116]. In a multicomponent Strecker reaction the syntheses of α-aminonitriles are generally done by condensation of aldehydes, ammonia and hydrogen cyanide [117][118]. The

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• study on the multicomponent reaction of thiazolium carbenes, benzils and water to yield 1,4-thiazin-3-ones [22]. Although the initial process producing the salt 12 was similar, the total mode of the two reactions was quite different, that is, stoichiometric vs catalytic reaction with respect to the

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

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• prehalogenation [16]. iii) The multicomponent method: only two strategies have been reported to the best of our knowledge. One is a combination of the Ugi reaction, which uses 2,4-dimethoxybenzylamine, arylglyoxal, carboxylic acid, and isonitrile as components, and a subsequent Robinson–Gabriel reaction [17]. The

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

Kinetic analysis of mechanoradical formation during the mechanolysis of dextran and glycogen

• Naoki Doi,
• Yasushi Sasai,
• Yukinori Yamauchi,
• Tetsuo Adachi,
• Masayuki Kuzuya and
• Shin-ichi Kondo

Beilstein J. Org. Chem. 2017, 13, 1174–1183, doi:10.3762/bjoc.13.116

• samples mechanically fractured at room temperature were multicomponent. The radical concentration of Dx and Gly mechanoradicals gradually decreased during vibratory milling after reaching the maximum value. Although the molecular weight of Dx or the particle diameter of Gly steeply diminished until

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• amine component in Ugi and Groebke–Blackburn–Bienaymé multicomponent reactions. The first example of an application of aminoazoles in an Ugi four-component reaction was discovered and novel features of a Groebke–Blackburn–Bienaymé cyclocondensation are established and discussed. The heterocycles

• chemical space with the aim of finding new biologically active structures. Modern chemistry offers several approaches, for instance, diversity oriented synthesis (DOS) for the generation of diverse compound libraries [6][7][8]. From this point of view, multicomponent reactions (MCRs), including isocyanide

• -pyrazole-4-carboxamide and 3-amino-5-methylisoxazole as an amine component in isocyanide-based multicomponent reactions was studied. Particularly, 5-amino-N-aryl-1H-pyrazole-4-carboxamide reacted as 1,3-binucleophile with aromatic aldehydes and alkylisocyanides with the formation of 3-(alkylamino)-N,2

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• conditions and a broad substrate scope, allowing for the rapid construction of structurally complex and diverse heterocycles in moderate to good yields. Keywords: Groebke–Blackburn–Bienaymé reaction; imidazo[1,2-a]pyridines; isoquinolines; multicomponent reaction; Ugi reaction; Introduction Imidazo[1,2-a

• clinical trials [14]. Multicomponent reactions (MCRs) [15][16][17][18][19], comprising three or more components, provide straightforward approaches to a wide range of heterocycles through the formation of various bonds in a one-pot process. These reactions not only greatly accelerate chemical syntheses [20

• discovery [22][23][24][25][26][27]. The Ugi reaction [28], an elegant pioneer of a multicomponent reaction, represents a powerful synthetic tool to assemble versatile peptide-like compounds. It has found many applications in the facile synthesis of natural products and biologically interesting molecules [29

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• -tetrafluorocyclohexane aldehydes 4 were used successfully in Ugi multicomponent reactions [11][12]. In this paper we report the preparation of amines of this series starting from a Birch reduction on benzonitrile, and with a similar methyl iodide quench, to generate amines 5, which are stable to hydrogen fluoride

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• for the synthesis of many alkaloids (Figure 1) [16]. To synthesize pyrazinoisoquinoline and its derivatives, various approaches such as the Ugi multicomponent reaction [17] amidoalkylation [18][19], N-acyliminium ion cyclization [20] and a radical cyclization [21] have been reported. To this end

• . Results and Discussion Piperazine-2,6-diones are usually synthesized through an Ugi [30] multicomponent approach. The condensation of primary amines with benzyliminodiacetic acid at high temperatures or CDI/THF at reflux leads also to the formation of piperazine-2,6-diones (Scheme 1). Using CDI/THF under

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• , (iii) reaction conditions can be examined very easily by real-time monitoring and (iv) integration of small amounts of products and intermediates would be possible [45]. Harbou et al. [46] performed a kinetic study on the multicomponent reaction of acetaldehyde and water to produce poly

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• cyanoacetates (α-cyanoesters). These compounds are particularly versatile reagents in organic synthesis including multicomponent reactions [109][110][111][112][113]. However, like decarboxylation for related malonic ester or acetoacetates, an easy access to the removal of the cyano group should encourage future

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• multicomponent reaction between an α-ketoacid, a diamine such as 8d, an aldehyde, and an isonitrile Nixey et al. [32] observed an amide intermediate prior to the formation of the heterocyclic quinoxalinone. An intermediate amide was also observed by Sherman et al. [33] in the reaction between an α-ketoacid

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• the Passerini reaction for the first time in a sequential multicomponent tandem reaction approach. After evaluation of all possible linker components and a suitable solvent system, highly functionalized dihydropyrimidone–α-acyloxycarboxamide compounds were obtained in good to excellent yields. In a

• first reaction step, different 3,4-dihydropyrimidin-2(1H)-one acids were synthesized, isolated and fully characterized. These products were subsequently used in a Passerini reaction utilizing a dichloromethane/dimethyl sulfoxide solvent mixture. By variation of the components in both multicomponent

• ; multicomponent reactions; Passerini reaction; tandem reactions; Introduction Multicomponent reactions (MCRs) are fascinating straightforward reactions for the preparation of diversely substituted products starting from three or more precursor molecules, forming products containing atoms/moieties of all

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• -pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

• . Conclusion In conclusion, the present work explores the use of 1,3-dipolar cycloaddition reactions for the regio- and stereospecific synthesis of functionalized spiropyrrolidines through a one-pot multicomponent reaction. This new route involving a vinyl framework gives rise to a wide array of novel

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

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

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• reaction for the construction of acyclic acylhydrazino-peptomers. The consecutive multicomponent reactions produced a variety of acylhydrazino-peptomers in moderate to excellent yields (47–90%). These compounds are multifunctional intermediates that can be further functionalized to obtain new

• multicomponent reactions (Scheme 1): the hydrazino-Ugi four-component reaction (HU-4CR) and the classical Ugi reaction (U-4CR). The strategy was based on the formation of an acylhydrazino-peptomer via an initial hydrazino-Ugi reaction followed by a hydrazinolysis reaction (or ester hydrolysis) and a subsequent

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• , pyrazole, and the Biginelli adduct as target ring systems with a view to discover new and greener strategies for their construction using multicomponent reactions. The application of the method is also extended to various heterocycles found in many natural products and pharmaceuticals. Keywords: atom

• greenness” as a core principle based on reaction design was applied to a database of named organic reactions [10] and multicomponent reactions (MCRs) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49

• rings. This will lead directly to the total number of possible multicomponent coupling assemblages or fragmentations of a given ring skeleton. The second is the enumeration of those partitions in a systematic manner so that a list of unique combinations for each type of ring partition can be obtained

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• cycloaddition one of the most valuable means of combinatorial chemistry. Such multicomponent reactions are characterized by productivity, operational simplicity, and efficiency [9][10][11][12][13]. A highly interesting class of heterocycles which is accessible through 1,3-dipolar cycloaddition reactions are

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• ; tetrahydroquinazoline; Introduction The synthesis of new molecules with potential biological activity through pot, atom and step-economic (PASE) reactions is an attractive green organic technique [1][2][3][4][5]. By the combination of multicomponent reactions (MCR) [6][7][8][9][10][11] with stepwise one-pot reactions