Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• aromatic, heteroaromatic and aliphatic amines in ethanol, under microwave heating, and without metal catalyst [83]. Very good yields of 35 are obtained in a very simple and cost-effective manner. A rather similar approach was disclosed shortly later by Han and co-workers [84], who used β-ketoacids (34 R3

• improvement on this multicomponent approach, making use of β-cyclodextrine as promoter, water as a solvent, and microwave heating (route C, Scheme 16) [98]. Under these neutral conditions, they prepared up to nineteen compounds (60–95%, R1 = H, Cl, R2 = alkyl, benzyl, aryl), including two derivatives

• comprising three palladium-catalysed reactions: Sonogashira, Heck and Suzuki–Miyaura (Scheme 37) [113][114][115]. In this methodology, N-arylpropiolamides 128 reacted with aryl iodides 129 and aryl- or styrylboronic acids 130 under microwave activation to yield 3-(diarylmethylene)oxindoles 131 or 3-(1,3

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• co-workers describing Zn(OTf)2-catalyzed, microwave-promoted conversion of a mixture of a secondary propargylamide and an amine into a trisubstituted imidazole 1 [1][2] inspired us to explore several variants of this methodology. Last year, we described the synthesis of differently substituted

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

• , Ukraine Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Katholieke Universiteit Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium Peoples' Friendship University of Russia (RUDN University) 6 Miklukho-Maklaya street, Moscow, 117198, Russia Enamine Ltd., 23 Chervonotkats’ka str., Kyiv

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

• amounts of each reagent. Neither room-temperature reactions nor reflux conditions led to satisfactory results. However, microwave heating of 11 at 120 °C for 30 min in trifluoroethanol as solvent allowed the obtention of the desired tetrazole-ketopiperazines 12 in yields ranging from 20–72% (1:1 to 9:1

• isocyanide-based multicomponent reactions in the synthesis of macrocycles containing a tetrazole nucleus [30]. The strategy was based on the use of α-isocyano-ω-carboxylic esters 71 via a microwave-mediated Ugi-azide reaction at the beginning of the synthesis and an intramolecular Ugi reaction of

• backbone could be easily exchanged. Later on, our group introduced the use of microwave heating to this same synthetic strategy for the synthesis of a cyclic peptoid (Scheme 18) [33]. The combination of these two tools (microwave heating and consecutive IMCRs) has proved to be a particularly attractive

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• supramolecular chemistry are dynamic combinatorial chemistry [11], subcomponent self-assembly approach [12][13][14], and systems chemistry [15][16][17][18], etc. There also has been growing interest towards exploration of nontraditional energy sources like visible light [19][20], microwave [21], mechanochemical

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• were unable to access 2 (Scheme 7). Instead, the major product isolated in both cases was novel heterocycle 35. It is likely that cleavage of one of the pivaloxymethyl groups, followed by intramolecular cyclisation, results in the formation of 35. Microwave heating of 33 in the presence of DBU also

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• ) by a reaction of 2-(2-bromoethyl)benzyl bromide with secondary amines under microwave irradiation followed by the decomposition of the products under the action of potassium tert-butoxide [46]. All of the above routes offer some advantages but they all are rather expensive. Thus, the initial stage of

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• -Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the macrolactamization of the

• degassed 1,2-dimethoxyethane (DME)/EtOH/H2O (9:9:2) under microwave irradiation at 120 °C for 30 min (Scheme 2). An aliquot of the resulting resin 5 was cleaved, and HPLC and mass spectrometry analysis of the crude reaction mixture revealed the formation of the biaryl cyclic peptide 6 in 18% purity. Mass

• )-βAla-Glu(Rink-MBHA)-OpNB (7), followed by microwave-assisted intramolecular Suzuki–Miyaura reaction, Boc group removal, and final macrolactamization. Boc-Tyr(3-B(OH)2,Me)-OH was prepared in solution through Miyaura borylation of Boc-Tyr(3-I,Me)-OMe [31], followed by hydrolysis of the pinacolate and

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• through a reaction of furfuryl alcohol with propargyl bromide, as is referred in the study of Cao et al. (Scheme 1) [17]. As a matter of fact, a modification of the purification step was done in order to quantitatively enhance the yield. An alternative solvent-free microwave-assisted organic synthesis

• -dimethylformamide system was tested according to the study of Fang et al. [25] revealing that the methoxy group in the meta-position of an electron-withdrawing substituents can be removed under microwave irradiation. However, when testing the system on 5b, no reaction occurred. Another experiment with lithium

• ) in the presence of different Brønsted acids. While investigating these conditions in combination with microwave irradiation (Scheme 4), the desired compound 4-HO-OPA (6) was successfully obtained in only 30 minutes, with a good yield (75%) when reacting with methanesulfonic acid (MsOH) as catalyst

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• Liangliang Song Guilong Tian Johan Van der Eycken Erik V. Van der Eycken Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001, Leuven, Belgium Laboratory for Organic and Bio-Organic Synthesis, Department of Organic and

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• bond formation was achieved using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl), 1-hydroxybenzotriazole (HOBt) and N,N-diisopropylethylamine (DIPEA) in DMF under microwave irradiation (Scheme 1). Racemic 1 was synthesized using tryptamine and (rac)-3-methyl-2-oxopentanoic acid

• phthalimides 16 and 23 [29]. These intermediary compounds 16 and 23 also allowed an N-methylation of the azaindole moiety with sodium hydride (NaH) and methyl iodide (MeI) to yield 17 and 24. By ethanolic hydrazinolysis and microwave irradiation the phthalimides (16, 17, 23, and 24) were deprotected yielding

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

• optimization, we improved the Ugi-macrocyclization procedure compared to our previous findings utilizing microwave irradiation (see Supporting Information File 1); Firstly, the corresponding amino acid was irradiated with indole-3-carboxaldehyde derivatives 6 using MeOH as solvent (5 mL) at 120 °C for 1 h

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• phosphorus atoms was synthesized by the microwave-assisted and catalyst-free Kabachnik–Fields reaction of (aminomethyl)phosphine oxides with paraformaldehyde and diphenylphosphine oxide. The three-component condensation of N,N-bis(phosphinoylmethyl)amine, paraformaldehyde and a secondary phosphine oxide

• affording N,N,N-tris(phosphinoylmethyl)amine derivatives was also elaborated. This method is a novel approach for the synthesis of the target products. Keywords: (aminomethyl)phosphine oxides; Kabachnik–Fields reaction; ligand; microwave; N,N-bis(phosphinoylmethyl)amines; N,N,N-tris(phosphinoylmethyl

• well as by the reaction of (hydroxymethyl)dibenzylphosphine oxide and aniline [8]. The condensation of butylamine, paraformaldehyde and di(p-tolyl)phosphine oxide to afford (butylaminomethyl)di(p-tolyl)phosphine oxide was also described [9]. A microwave (MW)-assisted, catalyst-free method was

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• Abstract The influence of microwave and ultrasonic irradiation on the performance of ammonium-tagged Ru-based catalysts in olefin metathesis transformations in aqueous media was studied. Differences in the catalytic activity in correlation with the nature of the present counter ion and the size of the N

• -heterocyclic carbene (NHC) ligand were revealed. The presented methodology allows for preparation of a variety of polar and non-polar metathesis products under environmentally friendly conditions. Keywords: catalysis; green chemistry; microwave; N-heterocyclic carbene; olefin metathesis; ruthenium; ultrasound

• interesting transformation. Furthermore, in the continuous search for new sustainable protocols for chemical reactions to induce new reactivates or reduce the energetic cost of the processes, the replacement of mechanical mixing and/or heating of the reacting species with microwave (μW) [46][47][48] and

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• Christiane Schultze Bernd Schmidt Universität Potsdam, Institut fuer Chemie, Karl-Liebknecht-Straße 24–25, D-14476 Potsdam-Golm, Germany 10.3762/bjoc.14.278 Abstract 8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination

• application of sequential one-pot transformations and motivated by the relevance of prenylated and other substituted coumarins in natural products and medicinal chemistry, we [27][28][29] and others [30] have investigated a microwave-promoted tandem reaction for the synthesis of 8-substituted coumarins over

• the past few years. Starting materials are allyl ethers of salicylic aldehydes or ketones 5 and the stable ylide ethyl (triphosphoranylidene)acetate (6), which upon microwave irradiation undergo a tandem Claisen rearrangement/Wittig olefination/cyclization sequence. This sequence was pioneered by the

MoO₃ on zeolites MCM-22, MCM-56 and 2D-MFI as catalysts for 1-octene metathesis

• Hynek Balcar,
• Martin Kubů,
• Naděžda Žilková and
• Mariya Shamzhy

Beilstein J. Org. Chem. 2018, 14, 2931–2939, doi:10.3762/bjoc.14.272

• OES (iCAP 7000, Thermo Scientific) was used. About 50 mg of the catalyst was digested in a mixture of HF, HCl, and HNO3 (1:2:2). The samples were placed in a Berghof microwave in a closed vessel at T = 140 °C for 35 min. Saturated solution of H3BO3 was then added for complexation of the excess of HF

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• undertook this reaction under argon in ethanol at 110 °C using a microwave reactor along with only one equivalent of DBU and these changes provided us with the ethyl ester 42 in a 51% yield. Finally, a far more simple procedure was found by just adding a catalytic amount of hydrogen chloride in 1,4-dioxane

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)4 as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3

• . Here we disclose the synthesis of novel 2- or 4-substituted 13α-estrone derivatives 8–13 via the Hirao reaction (Scheme 1). Diethyl phosphite (7a) or diphenylphosphine oxide (7b) were chosen as >P(O)H reagents and C–P couplings were planned under microwave irradiation using Pd-based catalysis

• , but the important benefits of microwave-irradiation have also been utilized in this field [29]. The optimization of reaction conditions was carried out using 2-bromo- or 2-iodo-13α-estrone 3-methyl ether (1 or 1I) as starting compounds and diethyl phosphite (7a) as the reagent (Table 1, Scheme 1). Two

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

• -methyl-1H-imidazolium chloride (66) ILs were used as excellent catalysts and the reaction medium for microwave synthesis of quinoline derivatives 65 from substituted anilines 15 and glycerol (64, Scheme 11). Some advantages of these catalytic systems include: elimination of oxidizing agents, ease of

• polyhydroquinoline derivatives 118 under microwave irradiation. Several substituted aldehydes 7 with dimedone (20), acetoacetate ester 34a, and ammonium acetate in ethanol under microwave irradiation were reacted to produce corresponding products in high yields. In addition to the catalytic role of strong acid

• -xylose (139) into furfural (140) was performed in water-CPME (1:3, v/v) and heated in a commercial monowave microwave oven in the presence of 10 wt % of 138 for 50 min. A maximum furfural yield of 76% was obtained. A new sulfonated graphene catalyst GR-SO3H (145) was prepared in some steps. A mixture of

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• -activated acylimidazole derivative was then converted to a β-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating

• the reference compound, cisplatin. Keywords: antiproliferative activity; Knorr reaction; microwave; pyrazol-5-ones; steroids; Introduction 17-exo-Heterocyclic androstanes with five or six-membered heterocyclic rings connected directly to C-17 of the sterane core represent a remarkable subclass of

• as the necessity of high temperature or prolonged reaction time and low yields of the desired products [14]. A rate acceleration and yield improvement could be achieved in some cases by performing the reactions under microwave (MW) conditions [15][16][17]. Especially with respect to pyrazol-5-ones

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• Xiaochen Du Jianjun Huang Anton A. Nechaev Ruwei Yao Jing Gong Erik V. Van der Eycken Olga P. Pereshivko Vsevolod A. Peshkov College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Dushu Lake Campus, Suzhou, 215123, China Laboratory for Organic & Microwave-Assisted

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• -aryl-2-iminoazacycloalkanes [84] and 2-oxazolines or their higher homologues [85], using polyphosphoric acid esters PPE (ethyl polyphosphate) [86] and PPSE (trimethylsilyl polyphosphate) [87] under microwave irradiation. PPE and PPSE are aprotic irreversible dehydrating agents of the Lewis acid-type

• esters are their low cost, operational simplicity and minimum environmental impact. Besides, their use together with microwave irradiation brings about shorter reaction times, cleaner crude products and consequently higher yields. On the basis of our previous work on DHQs [41], we explore herein the use

• ’-diacylation products were observed due to the low nucleophilicity of the secondary amino group, bearing a deactivating aromatic ring and all desired compounds were obtained with excellent yields (Table 2). Then, the microwave-assisted cyclization reaction leading to 3,4-dihydroquinazolines 1 was initially

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• , Claisen rearrangement (CR) of 77 under microwave irradiation (MWI) conditions on a silica gel support followed by O-allylation of the resulting CR product furnished diallyl compound 78. Treatment of diallyl compound 78 with G-I catalyst 1 delivered the expected naphthoxepine derivative 79 (96%). Next

• -Doctoral Fellow at the KU Leuven, Belgium under the EMINTE programme. During post-doctoral work his research work was related to organic synthesis under microwave reaction conditions. Presently, he is Research Associate with Prof. S. Kotha. His research interests include various transition-metal-catalyzed

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• synthesis of N-substituted 1,2,3-triazoles via the reactions of organoazides and the in situ prepared N,N-dimethylenaminones by 150 °C microwave irradiation and subsequent heating in toluene at 100 °C, providing an effective protocol of enaminone-based 1,2,3-triazole synthesis. Interestingly, our continuous

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• complete O-alkylation of the parent p-tert-butylcalix[4]arene was performed to give the products 5a,b. To achieve the selective distal alkylation of the macrocycle’s lower rim (compounds 1a,b) a microwave approach developed in our group was applied [32]. Then the di- and tetraalkylated products were