Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• microwave irradiation (80 °C, 150 W, 10 min, EtOH) proceeded with complete conversion (Scheme 3). It should be mentioned that the presence of water in this step resulted in a complex reaction mixture, moreover, the role of the reagent addition sequence was found to be crucial. The GBB reaction proceeded

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• (propargylthio)triazine 2, using CuI and diisopropylethylamine (DIPEA) in DMF under microwave irradiation at 110 °C for 15 min. It provided the peracetylated D-galactopyanosyl cluster 9 in 73% yield. The peracetyl D-glucopyranosyl cluster 10 was similarly obtained in 92% yield. The deacetylation of the

• equivalent of tris(propargylthio)triazine 2 in DMF, catalyzed by CuI and DIPEA under microwave irradiation. The incorporation of three carbohydrate residues was established unambiguously by ESIMS, 1H NMR, 13C NMR, and HMBC analysis, in particular based on the symmetry of the molecule, and on the lack of

• synthesizing mixed glycoclusters. Reducing the number of equivalents of glycosyl azide 7 to 2 equiv in the presence of CuI and DIPEA in DMF at 110 °C under microwave irradiation provided a statistical mixture with the bivalent cluster as the major product. The bis-D-galactosyl cluster 16 was thus isolated in

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• a means to overcome the low solubility of arylisoxazoles. The formation of an oxazine occurred only with phenyl diazoacetate 2a under these conditions. To overcome the inactivity of diazo compounds 2b,c the use of higher temperature and microwave irradiation were investigated, but only traces of

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• microwave irradiation (Scheme 1). Although a number of different reaction conditions were tested, we were not able to increase the yields in excess of 30%. Thus, with respect to the overall yields the successive approach 2→4→6→7 (overall yields: 6a: 62%, 6b: 43%) here is still advantageous compared to the

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• nucleoside analog was also prepared by this method. Very recently, Figueiredo et al. synthesized C-nucleosides 83 with the C-4 substituted 3,4-dihydropyrimidin-2(1H)-thione as a nucleobase (Scheme 31) [104]. The products were obtained as the C-4-(R) single diastereoisomers. The use of microwave irradiation

• -chlorobenzoic acid), followed by cyclization of the resulting diamide intermediate. After completion of the irradiation, products 110 were extracted with dichloromethane from the clay and crystallized from ethanol. The Montmorillonite K-10 clay–microwave irradiation reaction system was also used by Yadav and

• target compounds 113 and 114 were assembled from the three-component mixture of D-ribose, a derivative of salicylic aldehyde, and thiosemicarbazide under Lewis acid-catalysis and microwave irradiation. In comparison with analogous reactions carried out with mineral support (i.e., Montmorillonite K-10

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• and pyridine 7:3 as previously described for compound 8. The CuAAC “click” reaction was carried out as previously described for the galacto-clusters 9 and 13 and afforded the cone calix[4]arene 16 (Scheme 3) and 1,3-alternate calix[4]arene 19 (Scheme 4) in 46% isolated yield. Microwave irradiation

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• -glucopyranoside 6 To a solution of 4 (1.01 g, 1.83 mmol) in distilled DMF (15 mL), were added the azido-DCM 5 (2.23 g, 5.57 mmol), CuSO4 (110.9 mg, 0.44 mmol) and Na ascorbate (188 mg, 0.95 mmol). The reaction mixture was stirred at 70 °C during 5 min then at 130 °C during 30 to 45 min under microwave irradiation

• stirred at 110 °C during 15 min under microwave irradiation (700 rpm, monitoring by TLC). After cooling to room temperature, the reaction mixture was poured into 20 to 25 mL of distilled water. The precipitate was then filtred through cellulose acetate filter (porosity 2 µm) under vacuum and washed with

• (62.0 mg, 0.111 mmol), CuSO4 (2.5 mg, 0.010 mmol) and Na ascorbate (6.8 mg, 0.034 mmol). The reaction mixture was stirred at 70 °C during 5 min then at 130 °C during 30 to 45 min under microwave irradiation (700 rpm, monitoring by TLC), and poured into distilled water after cooling to room temperature

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• microwave irradiation resulted in the obtainment of the desired product in excellent yields of 91% and 95% in 12 h and 15 min, respectively. However, when the manufactured 4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde was treated with 1,2-diaminobenzene, the desired product was obtained in an

• inferior yield of 59% and 42% under conventional heating and microwave irradiation in 50 and 20 min, respectively (path A). On the other hand, when 4-(prop-2-yn-1-yloxy)benzaldehyde (2a) was first treated with 1,2-diaminobenzene in the presence of copper sulfate and D-glucose in a THF/H2O (2:1) mixture

• under conventional heating as well as microwave irradiation, the desired product was obtained in a better yield (70%) under conventional heating compared to microwave irradiation (54% yield). The compound was subsequently coupled with phenylazide (1a), which afforded the desired product in 67% and 78

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• 0.2 mL). The mixture was stirred and heated under microwave irradiation for 3 h at 80 °C. The mixture was concentrated, diluted in a 9:1:1 (v/v/v) mixture of MeCN/water/30 wt %-NH4OH and filtrated with the same eluent (25 mL) on a small pad of SiO2 (typically 1 cm thick), whose top surface became blue

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• reaction temperature (Table 1, entry 10) facilitated a slightly shorter reaction time. Based on this result, we decided to investigate the use of microwave irradiation, with the aim of further increasing the speed of the reaction. Running the reaction in methanol under microwave irradiation (300 W) at 65

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• the key reaction step. The copper-catalyzed regioselective click reaction was tremendously accelerated with assistance of microwave irradiation. Keywords: click conjugations; copper-catalyzed; microwave irradiation; multivalent glycosystems; neoglycoconjugates; one-pot; Introduction Oligosaccharides

• accelerated dramatically when microwave irradiation was used under 70 °C. To our delight under microwave conditions and in DMF with addition of 1 mol % of CuSO4·5H2O and 10 mol % of sodium ascorbate, a quantative yield of desired 3-tosylamino-2,3-dideoxyneoglycoconjugate 4a was obtained in 15 min (Table 1

• conjugations to microwave irradiation. All the reactions were completed in considerably shorter reaction times of less than 30 min for the Huisgen cycloaddition of alkenes and azides catalyzed by copper sulfate and sodium ascorbate, affording the corresponding products in good to excellent yields in each case

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• evolved [71]. In 1992, Yu and coworkers reported for the first time that microwave irradiation in combination with SPPS leads to enhanced reaction rates and hence, to a higher quality of the crude peptides [72]. Microwave energy is capable of activating any molecule containing a dipole moment, which is

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• product 7a (Table 2, entry 1). However, raising the temperature of the reaction and increasing the reaction time led to a significant increase in the conversion to product and an isolated yield of 82% (Table 2, entry 3). Further heating under pressure with microwave irradiation led to a decrease in yield

• -solvent as the solubility of the 3a was found to be greatest at 0.66 equivalents) in THF under microwave irradiation (Scheme 3), and afforded the desired product in moderate yield after just 0.5 h (longer reaction times led to degradation of the product). Extension of the chain to an ethyl group (i.e

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• performed with a palladium catalyst in the presence of a weak base. Sometimes microwave irradiation was used to shorten the reaction time. Gilbertson et al. have converted a series of vinyl triflates 80b into the corresponding vinyl phosphine boranes 81b through palladium catalysis with HPPh2 (Table 9) [160

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• the Ugi four-component reaction (U-4CR) [8][9][10][11][12][13][14]. It has been demonstrated that the combination of multicomponent reactions with the use of microwave irradiation is able to efficiently produce complex molecules with a reduced number of steps and short reaction times [15][16][17][18

• significantly reduced number of steps in short reaction times, and high yields in most of the steps. The strategic combination of two isocyanide-based multicomponent reactions and microwave irradiation makes this a very useful and attractive protocol. The obtained depsipeptoids will be tested for different

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect

• , rendering the method inadequate. Thus, we performed the reaction by microwave irradiation witth a solution of TPPF20 and the primary aminoalkyl dibenzylphosphoramidates in N-methyl-2-pyrrolidinone (NMP) as the solvent [9]. The conversion into the new porphyrin monoaminoalkyldibenzylphosphoramidate

• conjugates 1a–c was achieved in eight minutes in 20%, 42% and 24% yields, respectively. Longer reaction times led to the formation of polysubstituted products. A significant advantage for the reaction under microwave irradiation is its applicability even in the presence of functional groups, which are prone

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• desired DKPs products 168 in good to excellent yields (53–72%). Solvent effects of the Ugi reaction under microwave irradiation were considered by Santra and Andreana (Scheme 53) [146]. Protic solvents such as water gave rise to either 2.5-diketopiperazines 170 via an aza-Micheal reaction or 2-azaspiro

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• dehydrogenation with DBU in different solvents at various temperatures also failed and did not yield the required product. Attempted oxidation of compound 7 under microwave irradiation conditions was also not successful. Probably under all aforementioned conditions, formation of the stable enol 21 might have

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• reaction to yield 5-aryl-3,4-dihydro-1,8-naphthyridin-2(1H)-ones by an efficient synthetic route. Keywords: inverse-electron-demand Diels–Alder reaction; microwave irradiation; naphthyridin-2(1H)-ones; Sonogashira cross-coupling; 1,2,4-triazine; Introduction 1,8-Naphthyridine derivatives are an important

• -demand Diels–Alder reaction under microwave irradiation [22][23][24]. The use of 1,2,4-triazines in inverse electron-demand Diels–Alder reactions proved to be an efficient strategy for the construction of various heterocyclic compounds [25][26][27], such as azacarbazoles [28][29][30][31][32][33

• ], polycyclic condensed pyrazines [34][35], dihydropyrrolopyridines [36][37], thienopyridines and thiopyranopyridines [38][39], as well as furo- and pyranopyridines [22][23][24][40][41][42]. Reactions with microwave irradiation are well-known for their ability to reduce reaction times, increase product yields

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• acid, I2, Br2·SMe2 and BF3·OEt2, at temperatures ranging from rt to 80 °C. The transformations were tested under standard heating or microwave irradiation, with reaction times lasting form 30 min to 48 h. The imine 1a was generated in situ, using MS 4 Å, or previously prepared by condensation of the

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• tripeptide byproduct. Nucleophilic aromatic substitution (SNAr) chemistry contributes to creating useful materials. In 2005, Comer and Organ reported SNAr reactions of 2-fluoronitrobenzene using a flow microreactor system with microwave irradiation (Scheme 9) [69]. Toward making compound-libraries, Schwalbe

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• )3]}, are also well soluble in organic solvents and do thus allow for homogeneous CuAAC reactions. They were first applied in the synthesis of neoglycoconjugates in the presence of DIPEA or DBU under microwave irradiation in toluene solution [137]. However, a recent study by Díez-González has shown

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

•  2, entry 6). Meanwhile, reactions in THF or ethyl acetate resulted in marginally lower yields (Table 2, entries 8 and 9). Switching to water with assistance by microwave irradiation or performing the reaction in ethanol provided even unacceptable yields (Table 2, entries 10 and 11). Further, when

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• were accessed by intramolecular addition in excellent yields (Scheme 8b). The combined use of more electrophilic phosphite-gold complexes [41][42] and enabling techniques such as microwave irradiation [43] led to consistent improvement in efficiency of the catalytic system. In particular when (Ph3O

• )PAuOTf was employed under microwave irradiation with a catalyst loading as low as 0.05 mol %, the condensation of TsNH2 to norbornene was realized in quantitative yield. In addition, the introduction of carbene ligands [44] allowed performing the intramolecular hydroamination of N-alkenyl ureas

• obtained from moderate to good yields under microwave irradiation (DCE, Scheme 17c) [54]. Additionally, the stronger Lewis acid AuCl3/AgSbF6 was documented to catalyze the Markovnikov selective hydroarylation of aryl- and alkyl olefins with less-nucleophilic benzene derivatives and thiophene in good yields

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• synthesize 5,6-dihydroindolo[1,2-a]quinoxaline derivatives by CuI-catalyzed intramolecular N-arylation under microwave irradiation. This method rapidly afforded the tetracyclic products with good to excellent yields (83–97%) in short reaction times (45–60 min). Keywords: copper; 5,6-dihydroindolo[1,2-a

• ]quinoxaline; intramolecular N-arylation; microwave irradiation; Introduction The indole scaffold is considered as a privileged structure because of its ubiquitous presence in a large number of natural products and pharmaceutical agents [1][2][3][4][5][6]. In particular, indole-fused heterocycles have

• technology to conduct the intramolecular N-arylation. As a result, a similar yield was obtained under the same catalytic conditions when 1a was subjected to microwave irradiation for just one hour (Table 1, entry 2). Then, we tried to optimize the reaction conditions under microwave heating. At first