Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• as the main product, with the best yield being obtained in butanol (43%, Table 1, entry 11), however, with the formation of 6b occurring only in 10% yield. Switching to microwave irradiation formed exclusively 7b in 60% yield after 3 h (Table 1, entry 13). Note, that to check the effect of a shorter

• achieve the conformation of the proposed intermediate. We next examined the preparation of a set of indolones under the microwave conditions determined in Table 1, entry 13. These conditions were applied to several amines, producing exclusively the corresponding substituted indolones 7d and 7g–k in 48–56

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products. Keywords: microwave irradiation; N2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine

• green methodologies in synthetic heterocyclic chemistry. The utilization of microwave heating as an energy source has several advantages including operational simplicity, high reaction yields, enhanced rates, and increased energy efficiency [34][35][36][37][38][39][40]. In continuation of our efforts in

• 5-aminotetrazole (3) in pyridine under controlled microwave heating (Scheme 2). Results and Discussion With the initial aim of optimizing the reaction conditions, we began our study by reacting equimolar amounts of cyanamide 1, aromatic aldehydes 2, and 5-aminotetrazole (3) in pyridine and the

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• endotermic process is the rate-limiting step and long reaction times are generally associated to this. However, the reaction can be accelerated in conditions that facilitate the dissociation of CO ligands such as heating, microwave irradiation [37][38], visible light, or ultrasonication [39]. Alternatively

• cyclohexene, maleic anhydride, ethylene carbonate, and 1-octene, the desired products were not formed under the reaction conditions. In the same year, Helaja and co-workers examined the electronic effects of the alkyne substituent on the regioselectivity of the microwave-assisted PKR with norbornene [80]. The

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• be performed either at room temperature, in refluxing CH2Cl2 [19][28][29], at higher temperatures [1][30][31], and also under microwave conditions [32][33][34]. At lower temperatures or shorter reaction times an incomplete transesterification was reported [35]. The use of the low-boiling CH2Cl2 at

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• be produced by salt templating or ultrasonic spray pyrolysis as well as by microwave irradiation. The resulting activated carbon materials are characterized by a variety of techniques such as SEM, FTIR, nitrogen adsorption, Boehm titrations, adsorption of phenol, methylene blue and iodine, TPD, CHNS

• ]. Comparison of conventional and microwave heating Conventional heating for physical or chemical activation of the precursor materials has several drawbacks such as the non-uniform heating of the samples or a high energy demand due to long carbonization and activation times at high temperatures [103][104

• ]. Microwave irradiation is a promising alternative with some advantages. In contrast to conventional heating, which is based on the convection mechanism involving conduction and radiation, the sample can be heated uniformly and contactless by the heat generated from electromagnetic energy, resulting in

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• product 2-[18F]FPhe 46 in 43% yield, whereas under microwave irradiation a 34% yield was obtained. Under the optimized conditions, the enantiomeric purity was reported to be ≥94% ee [46] (Scheme 10). 1.3. Photooxidative cyanation of fluorinated benzylamine A convenient, protecting group-free, and

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• microwave irradiations. Taking advantage of the propargyl alcohol moiety present on commercially available steroids, this classical strategy was applied to mestranol and lynestrenol, giving a collection of new complex 17-spirosteroids. Keywords: diversity-oriented strategy; 17-ethynyl-17-hydroxysteroids

• Stewart–Grubbs catalyst combined with microwave heating at 120 °C (allyl ethers) or 170 °C (4-pentenyl ethers), demonstrating improved yields [77]. These temperatures were needed for the reaction to quickly go to completion. With 17-O-allylmestranol (5a), a rapid screening of the Stewart–Grubbs (SG

• study (Scheme 2). Thus, in the presence of G-II in toluene and under microwave heating, the reaction provided 17-spirosteroid dienes 8–10 in good yields (67–82%). Spirocyclic vinylcyclopentene substrates 8a,b and 9a,b were engaged in Diels–Alder reactions with a variety of dienophiles (11–15). The

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• using conventional or microwave methods had no effect on the conversion of intermediate 6 to compound 8. To explain the stable structure of the intermediate 6 (Figure 2a), energy minimization by MM2 was performed using the ChemBio3D Ultra 14.0 (CambridgeSoft Corporation, 2014) software force field [22

• yields (<19%) of the desired compound 8 were obtained after a longer reaction time (Table 2, entries 1–4). A further investigation of the reaction using microwave irradiation to heat at reflux temperature also failed to produce the target product (Table 2, entry 2). The intermediate 6 exhibited very low

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• solvents, such as dichloromethane, chloroform, tetrahydrofuran and toluene, allowing a full characterization by NMR analyses. Finally, the palladium-catalyzed cyclopentannulation of compound 5 with 1,2-diphenylethyne under microwave conditions using the catalyst system of [Pd2(dba)3] and P(o-tol)3 afforded

• -diphenylethyne, Pd2(dba)3, P(o-tol)3, KOAc, LiCl, DMF, 130 °C, microwave, 6 h, 5%. Supporting Information Supporting Information File 276: Experimental details, synthetic procedures, single crystal X-ray data for 1, detailed theoretical calculations, and analytical data for the compounds. Acknowledgements We

Synthesis of C₇₀-fragment buckybowls bearing alkoxy substituents

• Yumi Yakiyama,
• Shota Hishikawa and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2020, 16, 681–690, doi:10.3762/bjoc.16.66

• using 20 mol % of Pd(PPh3)2Cl2 and 150 mol % DBU in DMF at 150 °C under microwave irradiation conditions to afford the desired dimethoxy derivative 5a in 75% yield. In contrast, when the reaction of 4b was performed, not only the desired product 5b but also the unexpected regioisomer 5c was obtained

• . The temperature dependency of the product ratio between 5b and 5c was investigated and the results are shown in Table 1. The cyclization did not proceed under 140 °C, and at 140 °C the total yield is low (41% after 40 min microwave irradiation) but the ratio of 5b was the highest (5b/5c = 10:1). The

• microwave experiment was carried out with a Biotage Initiator Eight EXP. UV–vis absorption spectra were recorded on a JASCO V-670 spectrometer and a SHIMADZU UV-1800 spectrometer. Fluorescence spectra were recorded on a JASCO FP-6500 spectrometer. Melting points were determined on a Stanford Research

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• University of Arts and Sciences, Chongqing 402160, China Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 10.3762/bjoc.16.63 Abstract A facile microwave-assisted method for the synthesis of tetramic acid derivatives has been

• developed through an Ugi/Dieckmann cyclization strategy with DBU. This two-step one-pot procedure afforded the targeted tetramic acid analogues in good yields. With commercially available Ugi starting materials, microwave irradiation, a simple operation, excellent yields, and a broad scope, this reaction

• investigated the effect of different inorganic and organic bases (Table 1). It was interesting to note that all of the bases tested in the study afforded the desired enol tetramic acid derivative 7a after the reaction was heated under the microwave irradiation conditions. The ketone compound 6a could be the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• condensation of phenylacetylene and 1‐azido‐4‐nitrobenzene on a 4 mmol scale in EtOH/H2O (1:1) using 5 mol % of 87 was performed. After completion of the reaction, the heterogeneous catalyst was centrifuged and washed with ethyl acetate/water. This nanocatalyst could be reused in up to ten cycles. A microwave

• , trimethylsilylacetylene (TMSA) was selected for coupling with aryl iodides in the presence of a catalytic amount of Pd–Cu/C and PPh3 using Et2NH as a base in methanol at 120 °C under microwave irradiation for 20 min. In the next step, the azide derivative was added to the reaction mixture. Finally, the reaction mixture

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• , 58.39; H, 6.16; N, 6.08. 1-{2,6-(Diisopropyl)phenyl}-3-methyl-4-(4-tert-butylphenyl)-1,2,3-triazol-5-ylidene-(N,N’-bis{2,6-(diisopropyl)phenyl}imidazol-2-ylidene)copper(I) tetrafluoroborate, [Cu(IPr)(Triaz)]BF4 (5). In a glovebox, a microwave vial was charged with [Cu(Cl)(IPr)] (200.0 mg, 0.41 mmol

• ), NaOH (66.0 mg, 4 equiv, 1.64 mmol), Triaz.HBF4 (190.0 mg, 1 equiv, 0.41 mmol) and acetonitrile (2 mL). The reaction mixture was stirred during 2 h at 80 °C in a microwave. The solution was concentrated and diethyl ether (10 mL) was added. The precipitate was collected by filtration and washed with

• ). In a glovebox, a vial was charged with [Cu(Cl)(Triaz)] (150.0 mg, 0.32 mmol), NaOH (50 mg, 4 equiv, 1.28 mmol), Triaz.HBF4 (148 mg, 1 equiv, 0.32 mmol) and acetonitrile (2 mL). The reaction mixture was stirred during 2 h at 80 °C in a microwave. The solution was concentrated (0.5 mL) and diethyl

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• bipyridyl- (6), quinolinyl- (7), phenanthrolinyl- (8) and terpyridinyl- (9) phosphine ligands (Figure 1) [60]. Trofimov et al. [61][62] reported on an alternative reaction pathway using microwave heating for the synthesis of tris(2-pyridyl)phosphine in which white and red phosphorus were used. On treating

• treated with triflic anhydride to afford the corresponding triflate 55. Microwave-assisted reduction of compound 55 with pyridinium chloride afforded the α-chloropyridine derivative 56, which was further catalytically dehalogenated with palladium on carbon and formic acid to generate the pyridine scaffold

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• such interactions can be tuned, for example, by application of a condition-based divergence strategy [25], which is based on the variation of solvents, catalysts, and activation methods [16][26][27][28][29]. Thus, using nonclassical activation methods such as ultrasonication and microwave irradiation

• applying different temperatures in the range of 0–110 °C (both with the help of conventional heating and microwave irradiation) and by using different solvents and catalysts, such as HOAc, DMSO, primary alcohols with and without the presence of HCl, Yb(OTf)3, or Et3N. In all these cases, mixtures of

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• following the reported method [48] employing copper catalysis, and tested on our starting material upon variation of copper salts, solvents and temperature, resulting in the neat reaction under CuI catalysis being optimal when carried out for 2 h at 100 °C under microwave irradiation (see Supporting

• -accessible chemical space. Experimental General procedure (A) for the KA2 coupling reaction. CuI (0.2 equiv) was added in a dry sealed vial for microwave synthesis under a nitrogen flow. Then, ketone (1 equiv), alkyne (1.2 equiv) and amine (1.2 equiv) were successively added under a nitrogen flow, and the

• mixture was heated under microwave irradiation to 100 °C for 2 h. Then, EtOAc was added and the organic phase was washed with 5% NH4OH (3 × 20 mL) and brine. The organic phase was dried with Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography using the

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• -560, Brazil Universidade Federal de Campina Grande, Centro de Educação e Saúde: Cuité, Paraíba, Brazil 10.3762/bjoc.16.19 Abstract The propargylation of aldehydes promoted by microwave irradiation using allenylboron compounds in a chemo- and regioselective way is described. The corresponding products

• were obtained in short reaction time, high yield and purity without the need of any solvent when allenylboronic acid pinacol ester was used, or using a minimal amount of acetone when potassium allenyltrifluoroborate was used. Keywords: boron compounds; microwave; propargylation; regioselectivity

• pharmaceutical synthesis [29]. Moreover, the removal of tributyltin residues from reaction mixtures is also a major issue. The use of microwave irradiation for the formation of new C–C bonds is nowadays widely used and offers several advantages such as the increment in the product yield, reduction of reaction

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• -substituted tetrahydro-1,3-thiazepines by MW-assisted cyclization of 4-thioamidobutanols is presented. The acyclic precursors were prepared in high overall yields by an expeditious three-step diacylation/thionation/deprotection sequence from 4-aminobutanol. Microwave-assisted ring closure of 4-thioamido

• seven- and even eight-membered 1,3-diheterocycles had already been achieved by our group using the PPA ester/MW system [48][50][52][53]. Considering the lack of efficient methods for 4,5,6,7-tetrahydro-1,3-thiazepines, we decided to explore their synthesis by microwave-assisted ring closure of N-(4

• literature. The method involves as the key step the microwave-assisted ring closure of thioamido alcohols promoted by PPSE, presumably via an intramolecular SN2-type displacement of the PPSE-activated OH group. The precursors were easily prepared in a three-step sequence from 4-aminobutanol in high overall

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• ]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor. Keywords: α

• -phosphonoacrylates; α-phosphonopropionates; imidazo[1,2-a]pyridine; microwave-assisted reaction; Mizoroki–Heck reaction; Introduction In the last few decades, the Mizoroki–Heck reaction has become one of the main tools in organic synthesis. Its use for the functionalization of a wide range of compounds cannot be

• -bromoimidazo[1,2-a]pyridin-3-yl)-2-(diethoxyphosphoryl)acrylates 1, no desired product 3 was formed under standard heating conditions (Table 1, entry 1). Recently, multiple variants for the application of microwave heating for conducting Mizoroki–Heck reactions have been reported, including the use of

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• have reported one-pot multienzyme synthetic protocols for 2,7-anhydro-Neu5Ac [17][18][19]. Our group has developed one-pot syntheses of several anhydro sugars via microwave (MW)-assisted intramolecular anomeric protection (iMAP) of silylated sugars as well as ring-opening protocols for their 1,6

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• also be realized by DDQ-mediated dehydrogenation of chromanones under heating in dioxane (Scheme 1b) [3][59][60]. In 2005, Yang and co-workers reported that chromones could be formed by microwave irradiation of the corresponding chromanone reactants and N-bromosuccinimide (NBS) in the presence of a

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• bromide (6a) in the presence of Mo(CO)6 in acetonitrile at 90 °C under microwave irradiation (MWI) conditions to give the co-trimerized spiro derivative 8a (Scheme 2). The free NH moiety of thiazolidinedione 3 was alkylated using alkyl or aryl halides in the presence of Et3N using DCM as solvent. To our

• 125 MHz spectrometers using tetramethylsilane (TMS) as an internal standard and chloroform-d as a solvent. High resolution mass spectrometry (HRMS) was performed using a Bruker (Maxis Impact) or a Micromass Q-ToF spectrometer. The melting points recorded are uncorrected. The microwave used here was a

• Discover® SP by CEM Corporation and all the microwave reactions were performed under the standard method, where time and temperature can be monitored manually. Cell culture: Cells (Jurkat, K562, U937) were purchased from the Russian Cell Culture Collection (Institute of Cytology of the Russian Academy of

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• microwave reactor for 30–60 min, with product formation assessed by high field NMR analysis. Under these reaction conditions, m,p'-quaterphenyl is the equilibrium product. This isomer is unchanged by the reaction conditions and all other quaterphenyl isomers rearrange to m,p' as the dominant or sole product

• . This supports thermodynamic control based on carbocation energies. Keywords: arenium ion; carbocation; density functional theory; microwave reaction; rearrangement; superacid; Introduction Carbocations are enigmatic reactive intermediates of enduring importance in chemistry. No other reactive species

• conducted in the capped tube of a microwave reactor. With this approach, we can safely and reproducibly heat reactions to ca. 170 °C, so far without incident. Other more complex rearrangements are easily observed. In the binaphthyl series 7–9, three sequential rearrangements occur at ambient temperature