Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• and alkoxylcarbonyloxy groups generally require long heating times at elevated reaction temperatures (>140 °C) or microwave irradiation (Scheme 2a). In contrast, N-sulfonyloxyanilines are known to readily undergo the [3,3]-rearrangement during the preparation of the starting material below −20 °C due

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• permeable membrane reactors [46][47][48], high-pressure reactors utilizing back pressure regulators [49][50][51], reactors with different heating and cooling modes (e.g., inductive heating [11][52], microwave [53][54][55] etc.) and many more, also very special reactors [56] with other difficulties that need

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• microwave heating [7][8][9][10][11][12][13][14][15], ultrasonication [16][17][18], ligand-free methodologies [19][20][21][22][23][24][25] and the use of water-soluble palladium pre-catalysts/catalysts [26][27][28][29][30]. The latter is the preferred choice since it allows for the reusability of the

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• ) procedures [34]. Phenylglycine and norvaline derivatives were prepared on a CEM Discover microwave synthesizer, with diisopropyl carbodiimide (DIC) as the coupling reagent along with Oxyma Pure. The ratio of DIC:Oxyma Pure:AA was 3.6:3:3 dissolved in N,N-dimethylformamide (DMF) for a final DIC concentration

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• reported in the field of calixarene chemistry [66][73][74][75][76][77][78]. Unfortunately, this methodology led to poor yields and a lack of reproducibility in the case of calixarene 7 and c-[RGDfK]-alkyne 8, even when a microwave heating was used. We then evaluated the use of copper nanoparticles (CuNPs

• ), as these nanomaterials are known to catalyze efficiently a wide range of organic reactions and notably the azide–alkyne cycloaddition [79]. Calixarene 7 was reacted with a slight excess (5 equiv) of cyclopeptide 8 in the presence of CuNPs and the mixture was heated by microwave (100 W) at 50 °C for 1

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• quinoxalin-2-ylideneacetates [9], multicomponent Mannich–Ritter transformations of quinoxalin-2(1H)-ones under the action of nitriles and 3,4-dihydro-2H-pyran [10] and a microwave-assisted cascade strategy via in situ-generated N-acyliminium ion precursors and amines [11] (Figure 2). To develop a new

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• go to completion. The crude isolated products exhibited very low solubility in solvents usually recommended for standard N-acylations (acetone, THF, 1,4-dioxane, pyridine, etc.). Treatment of these acid chlorides with G-1 dendron D-N

  NH (3 equiv) under various conditions (microwave-assisted organic

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• catalyst loading required as well as recoverability and reusability without any significant loss of activity in terms of reaction time, selectivity and yield. For reactions that are sluggish and mostly require heating, microwave irradiation is reported to significantly improve reaction rates, selectivities

• electron rich ones such as p-methylthiophenol, giving the corresponding products in very high yields. Unlike in the microwave irradiation protocol, the reaction of aliphatic thiols with epoxides proceeded smoothly to give excellent yields. In another contribution, Su et al. carried out thiolysis of

• oxidation to β-hydroxy sulfoxides under microwave irradiation. Gallium triflate-catalyzed ring opening of epoxides and one-pot oxidation. Thiolysis of epoxides and one-pot oxidation to β-hydroxy sulfoxides using Ga(OTf)3 as a catalyst. Ring opening of epoxide using ionic liquids under solvent-free

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• -docking motifs via the phenyl and vinyl moieties, with an additional less populated OH∙∙∙P(phenyl)-bound isomer detected only by microwave spectroscopy. The correct prediction of the energetic order of the isomers using quantum-chemical calculations turns out to be challenging and succeeds with a

• Fourier transform microwave (CP-FTMW) spectroscopy. Comparing spectroscopic results with quantum-chemical calculations is often mandatory for the interpretation of experiments. Furthermore, such comparison enables a critical evaluation of the approximations used, comparing the relative stability of

• different binding motifs. In this paper, the first structural investigation on the complex of phenyl vinyl ether with methanol is presented. An established multi-spectroscopic approach [19][20] is used, coupling FTIR, IR/UV and microwave spectroscopy with theoretical treatments including dispersion

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• the microwave-assisted synthesis of substituted pyrazolo[1,5-a]pyrimidinones, a core scaffold in many bioactive and pharmaceutically relevant compounds, has been established. A variety of substituents was tolerated at the 2 and 5 positions, including functionalized aryls, heterocycles, and alkyl

• groups. Keywords: microwave-assisted synthesis; nitrogen-fused heterocycle; one-pot; pyrimidinone; Introduction The pyrazolo[1,5-a]pyrimidinone is a fused nitrogen-containing heterocyclic system and is of interest due to its role as a basic core scaffold in many bioactive and pharmaceutically relevant

• . Herein, we report such a strategy for the simple synthesis of functionalized pyrazolo[1,5-a]pyrimidinones that employs a one-pot microwave-assisted approach. Findings A number of synthetic approaches have been developed for the synthesis of privileged nitrogen-fused bicyclic systems such as the pyrazolo

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• sequence-specific DNA binding, the lack of viable strategies for facile synthesis of library of structural variants of these classes of conjugates remains a huge challenge for the researchers. In order to resolve this issue, Dervan et al. recently published a modular microwave-assisted Fmoc-based solid

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• A facile Pd-catalyzed C(sp2)–N coupling to provide a range of 2- or 4-[(subst.)phenyl]amino-13α-estrone derivatives has been achieved under microwave irradiation. The reactions were mediated with the use of Pd(OAc)2 as a catalyst and KOt-Bu as a base in the presence of X-Phos as a ligand. The

• with benzophenone imine and subsequent hydrogenolysis. Keywords: aminoestrones; Buchwald–Hartwig amination; 13α-estrone; functionalization; microwave assisted reactions; Introduction Aminoestrones are of particular interest thanks to their diverse biological applications [1][2][3][4]. There exist

• in the amination step [9]. They also found that X-Phos is an outstanding ligand with increased activity and stability compared to those based on BINAP [10]. There are a number of literature methods with respect to microwave-assisted Buchwald–Hartwig couplings [11][12][13]. Many publications have

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• al. compared the amount of energy required to effect permanganate-mediated oxidative self-coupling of p-toluidine using different energy inputs. Ball milling was significantly more efficient (up to an order of magnitude) than conventional heating, microwave or ultrasound inputs [36]. The reduction in

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• '-pyrrolidine]-2,5'-diones. Zhu et al. [38] reported 3-substituted-2-indolinones via a microwave-assisted post-Ugi-4CR/Buchwald–Hartwig reaction and another similar approach was illustrated by Van der Eycken et al. [39] for spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones. In previous efforts to study 3

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• the desired 1-amidoalkyl-2-naphthol derivatives. This second step can also be considered as a nucleophilic addition of the amide to the o-QM component. Various catalysts and conditions were used to optimize reaction conditions considering economical and environmental aspects. These include microwave

• as catalysts. These latest strategies provide efficient syntheses under mild conditions without using harsh chemicals. Furthermore, the application of microwave irradiation or sonication is also preferred to conventional heating methods to accelerate the reactions. Synthesis of aminoalkylphenols The

• performed in a microwave reactor to utilize the advantages of this method. As expected, reaction times shortened, while the products were isolated in higher yields in comparison with those found by conventional heating. The application of (4aS,8aS)-hexahydroquinoxalin-2-one served as the first example with

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• amine 9 to compound 11 in two steps. However, under microwave heating conditions, both couplings of the amino group with squarate, as well as methoxymethyl (MOM) deprotection was observed. To the best of our knowledge, there is no report describing methanolysis of MOM-groups under microwave conditions

• . This transformation is perhaps similar to acetal hydrolysis in neat water under microwave irradiation [41]. Because of this efficient process, compound 11 was isolated in one synthetic operation in 80% yield from amine 9. In the last step, precursor 11 reacted with either amine (R,R)-12 or (S,S)-12, to

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• closed screw cap vial to 100 °C for 1 min (color changed from yellow to deep red). A part of the catalyst mixture (0.2 mL) was added to a microwave glass vial containing a degassed mixture of 9d (33.1 mg, 0.1 mmol), 4-methoxyphenylboronic acid (22.8 mg, 0.15 mmol, 1.5 equiv) and cesium carbonate (100 mg

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• systems. In addition, a microwave-assisted Wolff–Kishner reduction has been examined with good results in a 30 seconds reaction [45]. Another option is the production of hydrazine in situ, using chemical methods. Also enzymatic activities towards hydrazine have been discovered [46], however, not enough

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -ketoesters and phenols (the Pechmann condensation) [17]. Recent studies for the metal-catalyzed reactions for the synthesis of the coumarin skeleton are as follows: the Yb(OTf)3-catalyzed microwave irradiation of phenols and propynoic acids [18], the Pd(OAc)2-catalyzed oxidative cyclocarbonylation of 2

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved. Keywords: continuous-flow; desulfurisation; norbornene-fused heterocycles; pyrimidinones; retro-Diels

• ] syntheses of heterocyclic compounds. The rDA products can be gained, due to a thermal [4 + 2]-cycloreversion, by distillation under reduced pressure [29], boiling in solvent [30][31], and applying microwave irradiation [32][33][34][35] or flash vacuum pyrolysis [35][36]. rDA reactions under mild conditions

• (DCB)], and under microwave (MW) conditions in DCB. In order to provide a rapid and efficient access to the desired pyrimidinones 9–14 (Scheme 1), we reinvestigated these rDA reactions by using another method involving flow chemistry. Therefore, a modular flow system was designed, equipped with a

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

• high regioselectivity. Working on similar lines Boruah et al. [49] further explored the reactivity of 5-aminopyrazoles 16 with β-halovinyl/aryl aldehydes 33 under conventional heating and microwave conditions in DMF and DMSO with Pd(OAC)2 (2.5 mol %) catalyst with PPh3 as ligand (Scheme 5

• ). Interestingly, high yields of the corresponding pyrazolo[3,4-b]pyridines 34 were obtained when reactions were carried under solvent-free microwave irradiation. The synthesized pyrazolo[3,4-b]pyridines have shown potential cytotoxic activity against cervical HeLa and prostate DU 205 cancer cell lines. A similar

• -arylmaleimides 44 in a solvent-free methodology based on microwave-assisted (80 W, 80 °C, 1.5 h) hetero-Diels–Alder reaction for the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 (Scheme 8). Jiang et al. [54] described the synthesis of macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 49 by the

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• yields, was effectively obtained in 86% yield by using an excess of KF in ethanol and microwave heating at 140 °C. Conveniently, at the same time all the three acetyl protecting groups were cleaved and the free nucleobase was isolated via precipitation. A 5´-DMTr protection followed by 2´-TBDMS

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• the surface of AuNPs [61]. Herein microwave-assisted CuAAC was used to attach a variety of alkyne derivatives (5, 8, and 18–23) to azide-functionalized AuNPs (Scheme 8). The use of the microwave heating for the CuAAC reduced the reaction time to 5–10 minutes, and also gave almost quantitative

• conversion of the azides to triazoles. However, significant particle decomposition and/or aggregation were observed when the AuNPs were heated for more than 15 minutes in the microwave reactor. Astruc and co-workers reported several modifications to try and increase the efficiency of CuAAC reactions of AuNPs

• ]. Surface modification of AuNPs using microwave-assisted CuAAC. Reagents and conditions: (a) HS(CH2)11N3, C6H6, rt, 7 h; (b) dioxane/t-BuOH/H2O or THF, CuSO4, sodium ascorbate, microwave heating (1000 W), 5–10 minutes [61]. AuNP functionalization and efficient CuAAC with a range of alkynes reported by

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• of the bisdioxines becomes severely hindered in cyclic derivatives, so that the 38-membered ring compound 32 requires microwave heating at 170 °C to form tetraoxaadamantane 33, and the catenated compound 36 and calix[6]arene derivative 37 did not form tetraoxaadamantanes. The reaction mechanisms of

• cyclic structure as in Scheme 10, the formation of tetraoxaadamantanes requires the addition of water from the concave inside. Thus, the bisdioxine 32 did not form a tetraoxaadamantane 33 under the usual reaction conditions, but this was finally achieved in 35% yield by microwave irradiation at 170 °C

• tetraoxaadamantanes. Inward-pointing isocyanate, urethane and carbamate groups in bisdioxines. The diisocyanate is obtained by Curtius and Hofmann rearrangements of the diazides and diamides [38][39]. Microwave-assisted tetraoxaadamantane formation. Cyclic bisdioxine ester derivative 34 forming a single mono

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• -protected glycine was condensed with proline methyl ester under microwave irradiation. Subsequent hydrolysis of the ester gave N-protected Gly-Pro-OH (6). Condensation of dipeptide 6 with 1 was achieved using the corresponding acid chloride. Deprotection of the amino group was achieved by treatment with

• = doublet, t = triplet, q = quartet, m = multiplet), and coupling constants (Hz). High-resolution mass spectroscopy (HRMS) experiments were performed with a double-focusing mass spectrometer with EI. Melting points were measured on Yanaco melting point apparatus MP-500V without correction. Microwave

• reactions were performed in microwave tubes with clip lids using a Biotage Initiator microwave reactor. Typical procedure for the Hiyama cross-coupling reaction Analogous as described in [24]. In a glovebox purged with argon gas, iodo aniline (1.0 mmol), (2-methylallyl)palladium(II) (0.1 mmol), CuF2 (2.0