A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• multiplet (3.17–3.25 ppm). The addition of trifluoroacetic acid did not have a significant effect on the position of the signals of these protons. Thus, the reaction of itaconimides 1 with diaminoimidazole 4 is a regioselective and chemoselective cascade process involving an initial C-addition of

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• azido-tetrazole equilibrium has been previously studied in detail [25]. The coupling between compound 13-15N2 and 1-adamantanol (14) was conducted in trifluoroacetic acid (TFA) solution under reflux. A general and convenient approach to the N-adamantylation of heterocycles involves a reaction with the

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• degradation under free radical chlorination conditions. However, no reactions were observed when RfnI were treated with Cl2 or NaOCl/HCl. Nonetheless, perfluoroalkyl iodides RfnI (n = 6–8, 10, 12) can be oxidized using various recipes (e.g., 80% H2O2 in trifluoroacetic acid anhydride) to the iodine(III) bis

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• 250 × 10 mm, 5 μm; Macherey-Nagel) using a gradient from 10% (v/v) MeOH in H2O (+ 0.1% trifluoroacetic acid) to 100% (v/v) MeOH over 30 min. The purity of the isolated herpetopanone determined by HPLC was >95% at all wavelengths (compared to sum of total peak areas). Agar diffusion assay The assay was

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• added to a solution of N-acetylproline in water (2.5 mL). The mixture was stirred at room temperature for 16 hours. Then, trifluoroacetic acid (0.1 mL) was added, and the mixture was stirred for an additional hour to quench residual diazo compound. The solution was then freeze-dried. Purification of the

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• -hydroxytryptophan derivative 79 using aminolysis and reduction with (CH3)3N·BH3 complex [47][49][69]. Acylation of 79 with pyruvoyl chloride gave amide 80, which was converted into dioxopiperazine 81 upon the action of trifluoroacetic acid. Subsequent water elimination furnished the title neoechinulin B analogue 77

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 between di-tert-butyl phosphite and either benzyl halide [137] (Michaelis–Becker reaction) or aldehyde [134] (Pudovik reaction) or using tris-tert-butyl phosphite (Abramov reaction) [135]. The elimination of the t-Bu moieties can be efficiently achieved in presence of trifluoroacetic acid (TFA

• diethyl phosphonate groups [204], other mild conditions, developed in the context of peptide chemistry, were reported. It is based on the use of trimethylsilyl trifluoromethanesulfonate (TMS-OTf) as silylating agent, trifluoroacetic acid (TFA) as acidic reagent, and dimethylsulfide (DMS) and m-cresol to

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• , then Tf2O, 46, −60 °C to 0 °C. Effects of anomeric leaving groups on glycosylation outcomes. Reagents and conditions: (a) Ph2SO, Tf2O, TTBP, CH2Cl2, −40 °C; then acceptor, −40 °C to rt, (b) 1-(benzenesulfinyl)piperidine, Tf2O, CH2Cl2, −60 °C, then acceptor, (c) 10% trifluoroacetic acid in Ac2O, 0 °C to

• ) acetone/trifluoroacetic acid, then F-SPE. Aglycon transfer from a thioglycosyl acceptor to an activated donor can occur during preactivation-based glycosylation reaction. This side reaction can be suppressed by tuning the reactivity of acceptor aglycon or manipulating the reaction temperature

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• trifluoroacetic acid [36]. Indeed, when 10a was treated with CF3CO2H in refluxing dichloromethane for 3 days, the deprotected sultam 23 was isolated in a good yield of 72% (Scheme 7). Conclusion In conclusion, the intramolecular palladium-catalyzed C-arylation of tertiary 1-(methoxycarbonyl)methanesulfonanilides

• can be considered as a viable approach to five- and six-membered benzannelated sultams. The 4-methoxybenzyl group is a suitable protective group for the sultam synthesis since it is stable under the reaction conditions and can be easily removed by acidolysis with trifluoroacetic acid. Structure of

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• could be improved to 5:1 by substituting p-toluenesulfonic acid with trifluoroacetic acid albeit with a loss of yield. When the p-nitrophenylamide 5p was subjected to the reaction conditions, the expected oxazoline 6p was not observed (Scheme 6). Instead, alcohol 8 was isolated in 66% yield. Presumably

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• %) without any other detectable product. However, the TLC analysis of the crude material, after staining with cerium molybdate, displayed a plethora of red-colored spots typical for 4-methoxybenzyloxycarbonyl (MeOZ) cleavage with trifluoroacetic acid, thus suggesting the formation of a 4-methoxybenzyl

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• (TMSCl) and trifluoroacetic acid (TFA) for this catalytic system to increase the ee value of the target product; however, the use of the additives proved ineffective (Table 1, entries 15–17). With the optimized reaction conditions established, we next investigated the substrate scope of 3-substituted

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• 4 was prepared by Sonogashira reaction of 3 with trimethylsilylacetylene. Subsequent deprotection of the TMS groups using tetra-n-butylammonium fluoride and saponification of the tert-butyl ester with trifluoroacetic acid resulted in the corresponding benzoic acid 6. The latter was coupled to 6

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• of the benzylic group with molecular hydrogen using Pd(OH)2/C as a catalyst in the presence of trifluoroacetic acid, b) reprotection of the amino group as benzylcarbamate by treatment of the crude reaction mixture with benzyl chloroformate in the presence of diisopropylethylamine, c) hydrolysis of

• the dioxolane moiety with trifluoroacetic acid, d) reconstruction of the dioxolane moiety by reaction of the diol with the corresponding dimethoxyacetal in the presence of SnCl2 and e) N-deprotection of the pyrrolidine by exposure of the benzylcarbamate to molecular hydrogen in the presence of

• for the diastereoselectivity and syn-enantioselectivity. On the other hand, in the presence of trifluoroacetic acid the reaction proceeded slowly and the diastereoselectivity decreased to some extent. The presence of an achiral thiourea did not improve the results. Finally, we considered the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• in the range of 10–880 nM [66]. The synthesized compounds have also shown a strong inhibition of tubulin polymerase with IC50 values in the range of 0.62–2.04 µM. In this synthesis, the chalcone 124 underwent a Nazarov cyclization in the presence of trifluoroacetic acid to give 1-indanone 125. 2

• interesting bromo reagent for further transformations, has been synthesized from chalcone 128 [67]. In this synthesis, a Nazarov reaction of chalcone 128, in the presence of trifluoroacetic acid, gave 6-methoxy-3-phenyl-1-indanone 129 in 88% yield followed by the reaction with bromine in diethyl ether to give

• the presence of trifluoroacetic acid (TFA) at 120 °C (4 hours). The authors have proved that the microwave heating would significantly shorten the reaction time up to 20 minutes under the same reaction conditions (TFA, 120 °C, Scheme 42). The cell growth inhibitory properties of the synthesized 1

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• assignment. The separation of the stereoisomers of dracocephins B 3a–d could be performed on an analytical Chiralpak IC column using the eluent acetonitrile/2-propanol/trifluoroacetic acid 90:10:0.1 (Figure 9a). Only partial separation could be achieved for the first two eluting stereosiomers, which was

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• treatment with 2 mL TFA (trifluoroacetic acid/iPr3SiH/H2O (90:9:1)) for three hours. The resin was washed twice with 1 mL TFA and DCM, and excess of solvent was removed by evaporation. The peptides were precipitated with cold Et2O, pelleted by centrifugation and dried by lyophilization. All peptides were

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• derivatives 3 we carried out the reaction of specially prepared 6-imino-2,7-dioxabicyclo[3.2.1]octane-3,3,4-tricarbonitrile 3h [21] with dry trifluoroacetic acid under anhydrous conditions (Table 2, entry 6). The successful implementation of this process and isolation of product 2h with good yield indicate

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• acidic conditions either failed to give any reaction at room temperature or afforded complex mixtures when heated. After some experimentation, we finally discovered that treatment of compound 2e with trifluoroacetic acid in dichloromethane at 45 °C gave an excellent yield of the β-trifluoroacetamido-α

• trifluoroacetate liberated in the previous step, to give 6. Alternatively, loss of a molecule of methanol from starting compound 2 would lead to intermediate 5 (see Scheme 3), whose reaction with trifluoroacetic acid would furnish 9. Neber-type chemistry would afford the oxonium species 10, which would finally be

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• oxidative fragmentation at the bridgehead position of adamantanes 157a,b. The reaction employed the trifluoroperacetic acid (TFPAA)/trifluoroacetic acid (TFAA) system and afforded compounds 158a,b in high yields (Scheme 46) [300]. This method for the insertion of an oxygen atom was applied to the oxidation

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• group uses a mixture of trifluoroacetic acid (TFA) and its anhydride (TFAA) as solvents. It has the advantage that the formed ester can be separated and hydrolyzed, followed by recycling of the free acid which potentially can be reused in the process [24][25][26][27][28][29][30]. Contrary to the

• CDCl3, where two different signals for the m-pyrimidine protons are observed. We recently reported that the dihalogenato complexes are active catalysts of the methane CH activation in trifluoroacetic acid [34]. Under the reaction conditions it seems likely, that an exchange of the chloro against a

• ). We could also confirm the formation of the desired product by a solid state structure (Figure 4). Typical reaction conditions of the catalytic CH activation are 30 atmospheres of methane under strongly oxidizing conditions (potassium peroxodisulfate, trifluoroacetic acid and its anhydride), where

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• obtained in 20% yield (Table 5, entry 1). While the yield was improved to 42% in the presence of 2.0 equiv DMSO (Table 5, entry 2), it decreased when 4.0 equiv DMSO were used (Table 5, entry 3). Since the solubility of 1 in trifluoroacetic acid is low, we envisaged that the addition of co-solvents would

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -phosphonates: A one-pot three-component synthesis of N-arylisoquinolone-1-phosphonates 119 through the Kabachnik–Fields reaction of ethyl 2-(2-formyl-4,5-dimethoxyphenyl)acetate (116) with anilines 117 and triethyl phosphite in the presence of trifluoroacetic acid as catalyst has been reported by Borse et al

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• (3Ai) was obtained, when the Kabachnik–Fields reaction was carried out in the presence of a catalytic amount of trifluoroacetic acid in refluxing acetonitrile. The same procedure, i.e., the Kabachnik–Fields reaction in the presence of trifluoroacetic acid, but in refluxing methanol has been

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• next reaction without further purification due to its low stability. The required amine 14 to be coupled to 13 was synthesized from Boc-protected β-alanine and pentylamine using a method reported by Hoegl et al. [11]. Deprotection of the Boc group with trifluoroacetic acid (TFA) provided the free amine