Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• of 1,2-oxyamino products. For example, most oxyamination methods are limited to the installation of amide or sulfonamide derivatives. The direct installation of electron-rich amino groups, especially tertiary cyclic amines, remains an unsolved problem. Furthermore, most methods employ inflexible

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• -pyrido-diazocine 46 with an excellent yield of 94% (Scheme 18) [56]. The presence of the two sulfonamide substituents on the pyridyl ring might decrease the basicity of the nitrogen atom thus allowing the metathesis to proceed. Steric hindrance due to the C2 substitution may also prevent the pyridine

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• depending on the properties of both aryl substrate and amide nucleophile (Scheme 10). It is worth to mention that Pan and co-workers recently disclosed N-fluorobenzene sulfonimides to be employed as the source of sulfonamide to enable the synthesis of N-heteroaryl sulfonimides via copper-catalyzed aryl C–H

• catalytic protocol was later developed by Mizuno et al. [74] for the amidation of terminal alkynes using lactam, sulfonamide or cyclic carbamates. The application of Cu(OH)2 as heterogeneous catalyst allowed the synthesis of ynamides 77 with moderate to excellent yield under air (Scheme 20). A latest work

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• -methoxynaphthalene-1-sulfonamide moiety that is connected by an internal double bond to a 2,4-dinitroaniline core, acting as a fluorescence quencher [17]. Both the sulfonamide of the fluorophore and the aniline group of the quencher bear another allyl group. Upon relay ring-closing metathesis, the fluorophore and

• was achieved relying on two converging synthons (Scheme 2). The fluorophore part of the molecule was synthesized starting from sodium 5-methoxynaphthalene-1-sulfonate (11), which was prepared according to a known procedure [25]. It was then transformed to the corresponding allyl sulfonamide 12 by

• platereader was used. N-Allyl-5-methoxynaphthalene-1-sulfonamide (12). To a DMF solution (30 mL) of sodium 5-methoxynaphthalene-1-sulfonate (11, 1.30 g, 5.00 mmol, 1.00 equiv), cooled on an ice bath, thionyl chloride (1.09 mL, 15.0 mmol, 3.00 equiv) was added dropwise. After the complete addition, the ice

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• skeletally diverse bi-, and tricyclic sultam derivatives (sulfonamide analogs) using norbornenyl sultam 272 as a core unit assembled by an intramolecular Diels–Alder (IMDA) reaction via a domino ROM–RCM–CM cascade. Diversity has been incorporated by using various cross-metathesis partners (Scheme 56). Basso

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. Keywords: ene-sulfonamide; imine

• the original substrates 1 by swapping the locations of the radical precursor (halide) and the radical acceptor (ene-sulfonamide). The expected products of these reactions, imines like 19, could possibly be used to make spirocyclic oxindole natural products like coerulescine [18], horsfiline [19][20

• needed for the radical precursors was made in high yield as shown in Scheme 3. Vilsmeier–Haack formylation [25] of ene-sulfonamide 20 was followed by sodium chlorite oxidation [26] of the resulting aldehyde (90% yield over two steps). The radical precursors 22–24 were readily made in 54–69% yield by

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• sulfonamide derivative in preparing glycophane molecule (Scheme 6). Haley and Langsdorf [90] have reported the synthesis of a cyclophane-containing octacobalt complex 49 using the Glaser–Eglinton coupling reaction [91] as a key step (Scheme 7). In this regard, palladium-catalyzed alkynylation of 1,4

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• as such electrophilic intermediates for an efficient intermolecular addition reaction. Addition reactions with N-alkyl-N-halosulfonamides to unsaturated compounds have not been examined in detail so far. In earlier works Komori added a secondary N-chloro-sulfonamide to 1-hexene under photoirridation

• an N-alkyl substituent, which we anticipated to generate readily from the corresponding N-chloroamides by electron transfer from copper(I) catalysts. Results and Discussion The N-chlorosulfonamides can be easily prepared by reaction of the sulfonamide with calcium hypochlorite and moist alumina [34

• better results whilst rising the temperature to 75 °C and adding an excess of styrene increased the yield to 43%. Under these conditions the N-chlorosulfonamide 2a was completely consumed, undesired products were the sulfonamide 1a as well as oligostyrenes. The oligomerisation should be slowed down by

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• kinetics. Keywords: azobenzene chemistry; enzyme inhibitors; human carbonic anhydrase II; sulfonamide; X-ray crystallography; Introduction Carbonic anhydrase (CA) is an ubiquitously found zinc-containing metalloenzyme with many isoforms, which all catalyze the conversion of carbon dioxide and water to

• (Figure 1b) [5]. Furthermore, sulfonamide-containing azobenzenes exhibit affinity and blocking ability for hCAII (Figure 1c) [6]. With our knowledge in azobenzene chemistry and photopharmacology, we aimed to further understand how electronic substitution patterns on azobenzenes correlate to changes in

• ). Another commonly used method is the condensation between anilines and aryl nitroso compounds, known as the Mills reaction. According to these transformations, nine sulfonamide containing azobenzenes 1a–i with different moieties in the 4´-position were synthesized. The substitution in the 4´-position will

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• 1,3-dipolar cycloaddition and reduction [34] (Figure 3). (−)-Tashiromine has been accessed through the ring closure of difunctionalized acyclic chiral sulfonamide-based β-amino acids [35], the cyclization of pyrrole derivatives with a chiral side-chain [36], or the enantioselective arylation of

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• ), deoxyvasicinone was subjected to a free-radical bromination using NBS and the subsequent treatment with NaOAc/AcOH as an acetoxylation reagent [12]. However, for most of these synthetic strategies harsh reaction conditions are a necessity, produce unstable sulfonamide anhydride intermediates [2][13], which are

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• reported that 4-amino-2-sulfanylphenol derivatives display highly specific protein kinase and angiogenesis inhibitory activities. Based on their previous findings, the structure of compound 24 was optimized by replacing the naphthalene by a phenolic skeleton and a sulfonamide fragment [52]. These compounds

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• . For comparison, we also synthesized and tested a bromine modified dansyl derivative N-(3-azidopropyl)-6-bromo-5-(dimethylamino)naphthalene-1-sulfonamide (BNS, 6, Figure 2). Dansyl chloride is brominated according to the literature [30] to produce 6-bromo-5-(dimethylamino)naphthalene-1-sulfonyl

• yield and compared it with other commercially available fluorophores of similar size (Figure 2). We chose N-(3-azidopropyl)-5-(dimethylamino)naphthalene-1-sulfonamide (DNS, 8) with a fluorophore system exhibiting a large stokes shift [1] suitable for fluorescence detection with UV filters

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

• converted to the corresponding sulfonamide with para-methoxyphenyl (PMP) sulfonyl chloride. Cleavage of the silyl ether moiety with TBAF gave primary alcohol 143, which was oxidized to the corresponding acid 144 by a two-step protocol consisting of treatment with Dess–Martin periodinane followed by Pinnick

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• must be activated as a sulfonamide (or acetamide) to produce the expected phosphoramidate [42]. The authors, who used a phase-transfer agent, postulated that this activation resulted from the increase of the acidity of the N–H bond despite the evident reduction of the nucleophilic character (Scheme 14

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

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• vigorous (~500 rpm) stirring, and the mixture was heated to 60 °C. After cooling to room temperature, the organic bromide 3 (7.5 mmol), the aldehyde 2 (2.5 mmol), the sulfonamide 1 (2.5 mmol), and cobalt bromide (0.25 g, 1.125 mmol) were added successively, and the resulting mixture was stirred for 10

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• method to alternative sulfonamide based diepoxides, focusing on one characteristic example. Furthermore, the polymerization of these types of diepoxides was investigated with lysine-based α-amino-ε-caprolactam through rheological measurements. Results and Discussion N,N'-(Hexane-1,6-diyl)bis(4

• -methylbenzenesulfonamide) (3), as precursor for the subsequent N-alkylation and further Prilezhaev epoxidation, was synthesized easily from p-toluenesulfonyl chloride (1) and hexamethylenediamine (2) [23]. The resulting crystalline sulfonamide was first described in 1927 prepared from 1,6-dibromohexane and p

• route for the synthesis of N,N'-(hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide) (6) via N-alkylation of N,N'-(hexane-1,6-diyl)bis(4-methylbenzenesulfonamide) (3) and further oxidation was described. For the first time, the CD-mediated N-alkylation of a sulfonamide was conducted

Novel supramolecular affinity materials based on (−)-isosteviol as molecular templates

• Christina Lohoelter,
• Malte Brutschy,
• Daniel Lubczyk and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2013, 9, 2821–2833, doi:10.3762/bjoc.9.317

• crystal microbalances. Based on the reported triamine all-syn-2a [40], 2a was brought to reaction with para-toluenesulfonyl chloride in order to equip the receptor scaffold with sulfonamide binding sites (Scheme 1). The reaction proceeds with a moderate yield of 32% under very mild reaction conditions

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

• , sulfonamide and amine substituents. The catalytic process is insensitive towards the presence of air and pH changes between pH 4 and 12 in a solvent mixture of water and tert-butanol. This strictly regioselective stepwise process gives the 1,4-disubstituted 1,2,3-triazole only and accelerates the reaction by

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• sulfonamide which can accelerate hydrolysis and catalytic turnover was also added to the reaction mixtures [26]. Yields for the dihydroxylation chemistry were variable (44–80%); even though they are diols, these small molecules proved volatile. Reproducible yields (>55%) could be achieved if care was taken

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• employing the Peterson protocol (TMSCH2CeCl2, THF, −78 °C; then TMEDA; then HF, MeCN, 25 °C, 64%) [36]. Towards this end the azide moiety was reduced and monoprotection of the so-obtained amine as a sulfonamide (LiAlH4, THF, 0 °C→25 °C; then benzenesulfonyl chloride, Et3N, DMF, 0 °C, 69%) gave 17

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• a double nucleophilic substitution between tosylamine and 2,3-bis-chloromethylpyridine (1.112) followed by catalytic reduction of the resulting bicycle using palladium on carbon in acetic acid (Scheme 20). As the corresponding sulfonamide 1.113 was found to be a crystalline solid a resolution using

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• tetrahydroimidazoles 72 based on intramolecular interception of the iminium ions by a tethered sulfonamide (71, Scheme 18) [86]. Ru(bpy)3Cl2 was employed as the photocatalyst with oxygen as the stoichiometric oxidant. The use of a base in an alcohol solvent, such as MeOH, was also the key to the success of this

• solvent. No external base was needed when the alcohol was the nucleophile. However, if the sulfonamide was the nucleophile, an external base such as t-BuOK was required presumably to increase the nucleophilicity of the sulfonamide. The Rueping group trapped the iminium ions using phosphites 76 to produce

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• electron-rich olefin was coupled to one of two competing nucleophiles, a sulfonamide and an alcohol (5). When the oxidation was run with 2,6-lutidine as a base (not shown), the reaction led to the formation of a radical cation from the electron-rich olefin followed by trapping by the alcohol nucleophile to

• form product 9. No product from sulfonamide trapping (8) was observed. However, when the reaction was run under more basic conditions (0.5 equivalents of lithium methoxide) cyclic voltammetry data indicated that the oxidative cyclizations were initiated by the oxidation of sulfonamide anion. This led

• to initial formation of N-localized radical 6. Depending on the reaction conditions, the experiment favoured either a sulfonamide or alcohol based cyclization. Density functional theory (DFT) calculations suggested that sulfonamide based cyclizations proceed by addition of the N-localized radical to