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

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• 36 underwent a ring-closure metathesis reaction in the presence of catalyst 37 under microwave irradiation to give lactam 38. Deprotection of the amine followed by acidic opening of the ring gave the (E)-monofluoroalkene 39 in good yield. The reaction was also performed on the racemic starting

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• were recorded on an automated melting point system with a heating rate of 1 °C/min and are uncorrected. Microwave optimisation reactions were performed in a Biotage® Initiator+ microwave system. Flow reactions were preformed using the pumping system of a Vapourtec R-Series modular flow chemistry system

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• –C6H4, 4-I–C6H4, 4-CH3–C6H4, 4-OCH3–C6H4, thien-2-yl, 4-Ph–C6H4, CH3) and 5-aminotetrazole, by using conventional heating in an oil bath or microwave irradiation, was performed in IL. Here, only the 5-trifluoromethyl-substituted tetrazolo[1,5-a]pyrimidines 6a–g were obtained in all cases. Some important

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• , there is a persistent incentive to find greener alternatives, which would reduce time and energy requirements as well as waste generated by these reactions. Among other non-conventional approaches such as microwave and ultrasound irradiation [7][12][13], mechanochemistry has emerged as a viable approach

• spectroscopy was performed on a Varian E-9 spectrometer, at room temperature. The measurements were obtained at the microwave frequency around 9.3 GHz with the magnetic field modulation amplitude of 0.5 mT. For detecting copper in the final products, ESR spectra were recorded by an X-band Bruker Elexsys 580 FT

• /CW spectrometer with a microwave frequency around 9.7 GHz. The measurements were performed at a modulation frequency of 100 kHz and a magnetic field modulation amplitude of 0.5 mT. The results are shown in Supporting Information File 1, Figure S21. X-ray crystal structure analysis. Single crystals of

Is the tungsten(IV) complex (NEt₄)₂[WO(mnt)₂] a functional analogue of acetylene hydratase?

• Matthias Schreyer and
• Lukas Hintermann

Beilstein J. Org. Chem. 2017, 13, 2332–2339, doi:10.3762/bjoc.13.230

• activity and regioselectivity of potential catalysts. The test system is based on heating substrate 10-undecyn-1-ol (4) together with a potential catalyst in degassed water–solvent mixtures to 160 °C for 15 min in a microwave reactor (Table 1). Analysis of the reaction mixture by 1H NMR against internal

• . More specifically, gold complex AuCl(PPh3) is not usually considered an alkyne hydration catalyst itself, but turns into a catalytically active gold(I) cation after activation with silver salt or Lewis acid [31][32][33][34]. Under the forcing microwave reaction conditions in aqueous methanol

• )pyridine) [24][25][26][28] expectedly brings about anti-Markovnikov hydration, with aldehyde 6 as major product. Table 1, entry 3 represents a first test of tungsten complex 1 in the microwave hydration protocol, at a fairly high catalyst loading of 20 mol %. Besides unchanged 4, the reaction mixture

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• microwave activation was reported to reduce the reaction time up to only 7 minutes [132]. For the mechanism of hydrolysis of phosphonate by hydrochloric acid, some works dedicated to assess the hydrolysis of trimethyl phosphate are instructive and can likely be extrapolated to phosphonate. When trimethyl

• microwave heating. The final product was isolated in 63% yield [223]. The Moedritzer–Irani reaction was also applied to introduce phosphonic acid functions on polymer or dendrimers possessing reactive amine. Accordingly, phosphonic acids were introduced on polyethyleneglycol 113 [188], polyethylene imine

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• yield of the cyclic ether was still low (Table 2, entry 6). Microwave heating was not helpful (Table 2, entry 7). The non-nucleophilic base DBU was not effective in promoting the cyclization, either (Table 2, entry 8). We observed small amounts of products arising from the dehydration of 15 in the 1H

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• of Fmoc-V-OH with H-IA-resin and for the deprotection of Fmoc-IA-resin that were performed during 90 min at room temperature, the coupling steps were performed at 70 °C for 7 min under microwave irradiation. The deprotection steps were carried out with piperidine/DMF 1:4 for 3 min at 70 °C. After the

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• application, glycosyl donor precursors were reacted with phthalic anhydride to afford the corresponding esters. The activation with thionyl chloride was used for tethering the donors to the glycosyl acceptor counterpart and the regioselectivity was controlled using tin-mediated coupling under microwave

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• potential from an environmental point-of-view since it is able to reduce solvent issues in chemical syntheses. The catalytic activity of the obtained nanocatalysts was investigated in both the oxidation of benzyl alcohol to benzaldehyde and in the alkylation of toluene with benzyl chloride. The microwave

• -assisted oxidation of benzyl alcohol reached 45% conversion after 10 min. The conversion of the alkylation of toluene in both microwave-assisted and conventional heating methods was higher than 99% after 3 min and 30 min, respectively. The transformation of benzyl alcohol and toluene into valuable product

• in both the oxidation and alkylation reaction reveals a potential method for the valorization of lignocellulosic biomass. Keywords: alkylation; benzyl alcohol; benzyl chloride; iron oxide; mechanochemistry; microwave-assisted oxidation; polysaccharide; toluene; Introduction Heterogeneous catalysis

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

• /energy, etc. Non-conventional energy sources for chemical reactions such as microwave, mechanical mixing, visible-light and ultrasound are becoming surge of interest to the chemist as alternative energy sources in laboratories [7]. By imposing these techniques innumerable chemical transformations have

• ][75][76]. In view of this, chemists have introduced alternative energy sources like, microwave, sonication, mechanomilling, etc. [12][27][77]. Su and co-workers reported a copper-catalyzed arylation of anilines using arylboronic acid under high speed ball-milling conditions. Using 1.0 equiv of Cu(OAc

• reaction medium, solvent-free synthesis, microwave synthesis, use of different Lewis acids FeCl3, NiCl2, BiCl3, InBr3, use of Brønsted acids PTSA, etc. are also reported [129][130]. Recently, Mal and co-workers reported a mechanochemical Biginelli reaction by a subcomponent synthesis approach [131][132