A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• -membered heterocycle containing two adjacent nitrogen atoms. Pyrazole Pyrazole is a well-studied 5-membered heterocycle that has been traditionally synthesized either via the Knorr [151] (1,3-diketone and hydrazine) or von Pechmann [152] (olefin and diazomethane followed by oxidation) strategies. Figure 7

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• at C-5. In fact, 1a and 1c were obtained through a two-step sequence starting with the methylation of (−)-1a and (+)-1c followed by a one-pot Mitsunobu esterification–hydrolysis as shown in Scheme 6. In detail, treatment of rosaprostols (−)-1a and (+)-1c with diazomethane gave the corresponding

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

• Katrina Tait,
• Oday Alrifai,
• Rebecca Boutin,
• Jamie Haner and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 2189–2196, doi:10.3762/bjoc.12.209

• . Oxabenzonorbornadiene 1 and its derivatives are first cyclopropanated with diazomethane under palladium catalysis to afford 8 in good to excellent yields [29]. Cyclopropanated 8 has been predicted to undergo three distinct ring-opening mechanisms (Scheme 3). The first ring-opening type (type 1) involves the attack of

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• generated stereocenters, we continued our synthesis with anhydrosugar 12 as its configurations are matching with that of target compound. Thus, TEMPO-mediated selective oxidation of the primary hydroxy group in 12 to acid functionality followed by esterification using diazomethane afforded azido methyl

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• (4b), respectively, and diazomethane at –60 °C in THF solution [6] (Scheme 1). After addition of an equimolar amount of a ferrocenyl hetaryl thioketone 1, the reaction mixture was slowly warmed to room temperature. The crude mixture was examined by 1H NMR spectroscopy, and in all cases only one single

• -Tetramethyl-8-thia-5,6-diazaspiro[3.4]oct-5-en-2-one (3c) [20] and spiro[1,3,4-thiadiazole-2(5H),2’-tricyclo[3.3.1.13,7]decane] (3d) [21] were obtained by known methods according to the literature protocols. Diazomethane was prepared in a 5 mmol scale either from N-nitroso-N-methylurea or from N

• commercially available. Preparation of diaryl-substituted 1,3-dithiolanes (5a–g) – General procedure: A solution of thioketone 4a or 4b (1 mmol) in THF (3 mL) was cooled to –75 °C (acetone/dry ice). Then, the mixture was treated with small portions of ethereal diazomethane solution, until the disappearance of

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as

• (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates

• assumption that they occur via diradical intermediates [13][14][15]. Reactions of aromatic thioketones with diazomethane are well established. For example, in the case of thiobenzophenone (1a), the reaction performed at –65 ºC occurs without evolution of N2 and the in situ formed 2,2-diphenyl-1,3,4

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• exo products in an 8:1 ratio (Scheme 8). In comparison, it is known that maleic anhydride in analogous reactions affords exclusively the endo adduct [29]. Attempts to facilitate the isolation of very polar maleic acid 4 from the reaction mixture by derivatization to dimethyl ester using diazomethane

• were not successful. The dimethyl maleate derivative was formed but was accompanied by the [3 + 2] cycloaddition product 22. With excess of diazomethane, clean and efficient formation of 22 was observed (Scheme 9). Acid 4 was stable in water, methanol, isopropylalcohol, boiling benzene, or boiling

• . Synthesis of maleic anhydride 20 and Diels–Alder adducts 21. Reaction of maleic acid 4 with diazomethane. Decarboxylation of maleic acid 4 to acrylic acid 23 in DMSO and the preparation of deuterium labelled 23. Calculated reaction coordinates of Diels–Alder reaction of 12 with cyclopentadiene.a Supporting

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• pyrroloquinone [60]. The halogen presumably increased the electron delocalization in the diene allowing the overlap of molecular orbitals. Synthesis of neoamphimedine (12) Method A: To prepare neoamphimedine, 4-methoxy-2,6-dinitrophenol was methylated with diazomethane and the product was partially reduced to

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• -workers led to a reassignment of its structure and that of the parent molecules, such as polyoxin A (69) [24][25][26]. The synthesis of the E-isomer of polyoximic acid started from protected D-serine 70, which was converted into diazoketone 71 by reacting a mixed anhydride with diazomethane (Scheme 10

• provided intermediate 165. Removal of the chiral auxiliary and generation of the second carboxy moiety was then achieved by ozonolysis of 165 and ensuing esterification with diazomethane to give diacid ester 166. Treatment of the latter with TBAF cleaved the TBDMS ether and gave a lactone intermediate

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• the corresponding acid chloride (oxalyl chloride, CH2Cl2, 25 °C; then diazomethane, THF, 25 °C, 85% yield for the two steps) [33]. The anticipated C–H insertion then proceeded uneventfully under oxygen-free conditions (cat. Rh2(OAc)4, CH2Cl2, 41 °C) [34][35] to give cyclopentanone 11 in 52% yield as a

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• optimized by replacing step c) CH2N2 (diazomethane) with TMSCHN2 (trimethylsilyl diazomethane). This intermediate was transformed into intermediate 17 by a Horner–Wadsworth–Emmons reaction [23][24], thereby obtaining 17 as the single E-isomer in 68% yield after purification by flash chromatography (Scheme 3

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• reaction between bis(trimethylsiloxy)phosphine and the dibromide 50 followed by the esterification of the phosphinic acid using diazomethane (Scheme 21) [32]. The heterocyclization step followed methodology initially introduced by Frost et al [33]. Compound 51 was subsequently converted into the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• tetracycle 283. The carboxylic acid was converted into the corresponding acyl chloride, followed by addition of diazomethane and subsequent Arndt–Eistert homologation [215] to obtain methyl ester 284. Claisen condensation furnished the intermediate β-cyano-ketone, which was subjected to diazotransfer

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• natural product. To unambiguously prove the substitution pattern at the aromatic ring system, the phenolic OH-group was selectively methylated using diazomethane. The resulting methyl ether was irradiated in a 1D NOE experiment, which resulted in the expected strong increase of the proton bound to C-6

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• dichloromethane (Scheme 4). Compound 3 was obtained with a short reaction time and a high yield (91%). The ester derivative methyl 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobutanoate (5) was prepared by the addition of a diethyl ether solution of diazomethane to a suspension of amide 3. The ester

• -oxobutanoate (5) A suspension of 0.3 g (0.94 mmol) of 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobutanoic acid (3) in 10 mL of diethyl ether was cooled in an ice bath, and a solution of diazomethane in diethyl ether 2.5 N was added dropwise until the white solid disappeared, and the gas

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• procedure starting from isochromanone and trimethylsilyl-diazomethane [33]. The initially formed alcohols 23 were again converted into the respective iodides 24 as described before and subsequently substituted with diisopropylsilylacetylene 25 [34] providing five different dialkynes 16, each of them with a

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• of the β-aminoynone 2 began with the Arndt–Eistert homologation [23] of N-Boc-protected D-alanine (Scheme 3). Thus, the N-Boc-D-alanine was treated with isobutyl chloroformate at 0 °C in THF/diethyl ether followed by the addition of diazomethane to afford the corresponding diazoketone. The Wolff

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• ); flow chemistry; microreactor technology; Introduction Diazo compounds are frequently used versatile building blocks in organic chemistry [1][2]. From this class of compounds diazomethane and ethyl diazoacetate (1, EDA) are arguably the synthetically most useful ones. Due to the potentially explosive

• nature of diazomethane and EDA [3][4][5], however, synthetic routes that involve large scale batchwise handling of such diazo compounds is generally avoided in industrial processes. With the advent of continuous processing over the past decade, new approaches have appeared to conceptually change the way

• ][7][8]. While the synthesis of diazomethane has been extensively explored in batch [9] and in continuous-flow reactors [10][11], EDA is synthesized via different routes in batch [12][13], but relatively little is known about continuous-flow approaches [14]. Considering the importance of EDA in a wide

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• resulted from heating 24 and 193 together [134]. Finally, as shown by Lüttke and Heinrich, the cyclopropanation of the parent system 2 with diazomethane/Cu2Cl2 provided a mixture of twelve cyclopropanation products in very good yield (ca. 90%), from the mono adduct 195 to the dispiro compound 196, i.e. the

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• than for DOI itself. Keywords: cyclopropanation; diazomethane; hallucinogen; 5-HT2A agonist; receptor probe; trans-2-phenylcyclopropylamines; Introduction Among the molecules that have proven very valuable to neuroscientists studying brain serotonin systems is the substituted phenethylamine

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• prepared from the respective β-amino acids by Arndt–Eistert homologation [17][18][19]. The β-amino acids were transformed into the respective diazoketones with isobutyl chloroformate, triethylamine and diazomethane. The ketones were further converted into the β-amino acids by Wolff rearrangement using

• solution of diazomethane (181 mL, 54.2 mmol, 2.00 equiv) in Et2O was added. After 15 min, the reaction mixture was stirred for an additional 6 h at room temperature. Excess diazomethane was decomposed by dropwise addition of AcOH. The solvent was removed under reduced pressure, and the residue was

Equilibrium constants and protonation site for N-methylbenzenesulfonamides

• José A. Moreira,
• Ana M. Rosa da Costa,
• Luis García-Río and
• Márcia Pessêgo

Beilstein J. Org. Chem. 2011, 7, 1732–1738, doi:10.3762/bjoc.7.203

• importance in the studies of the nitroso-group transfer mechanism from 1. Such compounds react with a variety of nucleophiles: In the presence of HO− or EtO−, which attack their SO2 group, decomposition to afford diazomethane occurs [1][2]. In acidic medium, they undergo denitrosation to the corresponding N

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• dibenzobarrelene derivative 1c which forms the chiral ammonium carboxylate 1c-P with (S)-proline (Scheme 2). After irradiation, acidic workup and subsequent esterification with diazomethane, the dibenzosemibullvalene 2c was obtained with high enantiomeric excess (>95% ee) [35][36]. Interestingly, several

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• diazomethane, generated in situ from N-methyl-N-nitroso-p-toluenesulfonamide (Diazald®) [56]. Homoadamantanone 3 was first reduced to the alcohol 4 [57][58][59] and subsequently converted to homoadamantyl phthalimide 5 in moderate yield via the Mitsunobu protocol [60] (Scheme 2). To get more insight into the