Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• basic ion exchange resin in methanol. The resin was filtered off and the solvent removed under reduced pressure. The primary amine was then dried under vacuum together with the diazirine 8 [28] (56.0 mg, 250 µmol) und HATU (114 mg, 300 µmol) for 30 min. The substances were dissolved in dry DMF (10 mL

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• one of an additional hydrophilic primary amine group. In a second series of tests we considered a set of dyes. In particular, we selected probe molecules having diverse structural frameworks, namely an acridinium derivative (toluidine blue, 6), a diazoic (methyl orange, 7), a triarylmethane

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric synthesis. In 2013, we described a novel class of calix[4]arene-based chiral primary amine–thiourea catalysts 47a and 47b derived from p-tert-butylcalix[4]arene (Figure 7) [49]. To evaluate the catalytic efficiency, bifunctional catalysts were applied to promote the Michael addition of aldehydes

• of the achiral calixarene platform, the monomeric analogue carrying both thiourea and primary amine subunits was also prepared and used in the control experiments. Under optimal reaction conditions, the noncyclic analogue afforded the product in lower yields and enantioselectivities (52% yield, 89

• % ee), which displayed the importance of the calix[4]arene skeleton. We also employed calixarene-based chiral primary amine thioureas 47a and 47b in the enantioselective Michael addition of α,α-disubstituted aldehydes 51 to maleimides 52 (Scheme 14) [50]. The reactions proceeded under mild conditions

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• Mannich reaction of N-Boc-isatin imines 3 with aldehydes, such as acetaldehyde (15a) [39]. When these reactions were catalyzed by simple chiral primary amine 16 in aqueous THF at 0 °C, they led to the corresponding chiral Mannich products 17 in good yields (74–81%) and uniformly excellent

• acetylacetone catalyzed by a cinchona alkaloid-derived squaramide. Mannich reaction of isatin-derived benzhydrylketimines with trimethylsiloxyfuran catalyzed by a phosphoric acid. Mannich reaction of N-Boc-isatin imines with acetaldehyde catalyzed by a primary amine. Mannich reaction of N-Cbz-isatin imines with

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• reported a novel multicomponent reaction for the synthesis of S-trifluoromethyl dithiocarbamates from secondary amines, CS2 and Togni's reagent in moderate to good yields. Under similar conditions, a primary amine afforded the corresponding isothiocyanate in excellent yield. The presence of dithiocarbamate

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• by analytical HPLC. After complete conversion, PPh3 was added directly to the reaction mixture at −78 °C. After addition of water and stirring for two hours, the primary amine 7wy was isolated in 86% yield. This procedure led to the ornithine analogous propargylamine 7wy, which was reacted with Boc

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

• reaction, is also known as the Moedritzer–Irani reaction since it was first reported by these authors in 1966 [219]. When primary amine is used, the reaction produces a bis-phosphonic acid since the secondary amine that is generated in situ is more reactive than the starting primary amine [220]. In

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• resulted in the discovery of an alternative mechanistic pathway. Apparently, in this case the primary amine moiety in intermediate 4 preferred a nucleophilic attack on the keto function, affording bridged hemiaminal structures 5 as kinetic products (Scheme 1) [42]. Upon extended heating, however

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• demonstrate the regiochemistry of the reaction. These cascade reactions proceed first through a Michael addition of the primary amine on the enone, followed by an intramolecular cyclization by the pyridine/pyrimidine nucleus. Unfortunately, no crystal structure could be obtained for the imidazopyrimidines and

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

• -promoted three-component Hantzsch pyrrole synthesis under ball-milling conditions [121]. A ketone in presence of N-iodosuccinimide (NIS) and p-toluenesulfonic acid led to α-iodoketone in 1 h. Subsequent addition of the primary amine, β-dicarbonyl compound, 5 mol % CAN and 1 equiv silver nitrate led to the

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• in the solid-state before having been exposed to microwave irradiation for 1.5–4.5 minutes. In their paper, the authors state: "Aryl isothiocyanate (1 mmol) and aromatic primary amine (1 mmol) were mixed thoroughly in an agate mortar" [33]. Considering the established reactivity pattern of electron

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• see Supporting Information File 1. We could access pure 8 by reacting 7 and formaldehyde under reductive conditions. The reaction product 8 kept the original configuration of its parenting analogue, amine 7, because the reaction between such primary amine 7 and formaldehyde occurs via an imine

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• exocyclic NH2 group and an endocyclic nucleophilic center, they can act both as primary amines and as 1,3-binucleophiles, therefore, their treatments with isocyanides, aldehydes and carboxylic acids may proceed either as Ugi-4CR (aminoazole – primary amine, acid – reagent) or as GBB-3CR (aminoazole – 1,3

• aldehydes and alkylisocyanides giving the product resulting from GBB-3CR. On the other hand, 3-amino-5-methylisoxazole in MCRs often acted as primary amine [102][103][104][105][106], that was confirmed in our case by treatment with aromatic aldehydes, alkylisocyanides and phenylpropiolic acid resulting in

• -diaryl-1H-imidazo[1,2-b]pyrazole-7-carboxamides (Groebke–Blackburn–Bienaymé reaction). In contrast, 3-amino-5-methylisoxazole acted as a primary amine in Ugi four-component reaction with aromatic aldehydes, phenylpropiolic acid and tert-butylisocyanide giving N-(1-arylethyl-2-(tert-butylamino)-2-oxo)-N

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• several primary amine motifs, largely due to inefficient sulfonylation. Here we show that using the superior nucleophilic base DMAP instead of the commonly used base collidine as a sulfonylation additive is essential for the introduction of the o-NBS group to these amine motifs. DFT calculations provide

• of DMAP (Figure 1D). In the first part of the suggested mechanism, the pyridine base substitutes the chloride to form a sulfonylpyridinium intermediate. This intermediate makes the sulfonyl group a better electrophile, hence, the attack of the primary amine in the second part of the mechanism becomes

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• Herein, we report the development of a synthetic strategy using [4 + 2]-cycloaddition reactions to yield endoperoxides 18–23 that contain a protected primary amine. Such intermediates serve as useful new building blocks for organic synthesis. Preliminary exploration of the chemistry of these compounds

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• reaction was carried out with N-benzenesulfonyliminodiacetic acid, a primary amine and CDI (2 equiv) in THF, the corresponding piperazine-2,6-dione 7a was obtained in 21% yield at room temperature (Table 1, entry 4). To facilitate the peptide bond formation DMAP has been used in conjuncture with coupling

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• -sulfamoylbenzamide analogues a) Continuous process with primary amines as F1: Triethylamine and a primary amine (F1) were dissolved in acetonitrile (c = 40 mM), m-chlorosulfonylbenzoyl chloride (F2) was dissolved in the same solvent in a separate volumetric flask (c = 40 mM). A third solution was prepared with

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

• recently reported that L-proline-catalysed direct aldol reactions may be successfully carried out also in deep eutectic solvents (DESs) [20][21][22]. Recently, our group reported on the possibility of running organocatalyzed, stereoselective reactions in DESs, promoted by an enantiopure primary amine, with

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• (from 82% to 95%). The flow rate of the reactants (diazotized primary amine and coupler) was also investigated as mentioned earlier on. As is shown in Figure 4, based on the predicted conversion, there is no difference in carrying out the reaction at either 0.03 mL/min or 0.7 mL/min. Moving on to the

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• in moderate 62% and 68% yields. In order to access available PEG-HMBPs functionalized with a primary amine or a carboxylic acid group usable in peptidic coupling with various molecules for example, the HMBP-PEG-COOH 23 was synthesized (Scheme 5). This compound was obtained in six steps starting from

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• protonation of vinyl ketones. Using primary amine catalyst (S,S)-119, the authors were able to catalyze the Friedel–Crafts addition of indoles 117 to vinyl ketones 118 followed by enantioselective protonation (Scheme 27) [52]. During optimization it was found that addition of a weak acid, 2-naphthoic acid

• review, Lou and co-workers reported an additional example of conjugate addition–enantioselective protonation involving an α,β-unsaturated ketone. In the new report, a chiral primary amine catalyzed conjugate addition of a 1,3-diketone nucleophile into an in situ generated ortho-quinone methide was

• ketones by enamine catalysis. Curtin–Hammett controlled enantioselective addition of indole. Luo and Cheng’s enantioselective additions to α-branched vinyl ketones. Lou’s reduction–conjugate addition–enantioselective protonation. Luo and Cheng’s primary amine-catalyzed addition of indoles to α-substituted

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• sulfinamides [48]. The application of this method to the synthesis of our chiral sulfoxide tethers is presented in Scheme 4. Tosyl protection of the primary amine of (+)-norephedrine and treatment with thionyl chloride furnishes chiral oxathiazolidine 2-oxide 7 as a single diastereomer in 87% yield over two

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• turn be synthesised by an aminolysis/oxidation/olefination sequence of the terminal alcohol 6, following traceless nitro group removal. 5-Nitropiperidin-2-one 6 in turn could be accessed by a nitro-Mannich lactamisation cascade reaction between Michael adduct 7, formaldehyde and a suitable primary

• amine, following our well-established protocol [6][7][8][9][10][11][12]. The key quaternary stereocentre of keramaphidin B, we envisaged, would be installed through an enantio- and diastereoselective organocatalytic Michael addition [13][14][15] between pronucleophile 8 and the known substituted furanyl

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• -derived primary amine catalysts (cat. 15 and 16) and achieved the asymmetric aldol reaction of 1,1-dimethoxyacetone with isatins (Scheme 30) [46]. The reactions were carried out at room temperature using 10% catalyst loading and trichloroacetic acid (TCA) as the additive, affording the corresponding 3

• -hydroxyoxindoles in excellent yields (up to 96% yield) and with high enantioselectivies (up to 97% ee), even for N-unsubstituted isatin derivatives. Besides, this protocol showed a broad substrate scope and good tolerance toward different functional groups. TCA promoted the formation of an enamine from the primary

• amine of the catalyst and ketone substrate and protonation of the tertiary amino group. The protonated amine then served as hydrogen bond donor to activate the carbonyl group of isatin substrates, thereby facilitating the aldol addition. Interestingly, the authors obtained the R-/S-enantiomer by using

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• deprotection with iodine instead of mercury compounds) we have improved the synthesis of aldehyde 9. The latter compound was then transformed to the protected ribitylamine 10 via the oxime, which was reduced with LiAlH4. Primary amine 10 was then converted with chlorouracil 3, which was actually the key