An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• ][4]. Among various nitrogen-containing heterocyclic compounds, pyridine and quinolines are readily found in bioactive compounds [5]. The functionalization of alkylpyridines and quinolines is significant and plays a remarkable role in the efficient drug design [6][7][8]. Due to their conformational

• functionalization [21][22]. The synthesis of pyridine and related azaarene derivatives involve the C(sp3)–H activation of 2-methylpyridines using different transition-metal compounds, Lewis acids, and Brønsted acids [23][24][25][26][27][28]. Recently, C(sp3)–H functionalizations of methylazaarenes with isatins and

• achieved from other starting materials, such as 2-methyl-6-(phenylethynyl)pyridine [36], 2,6-dimethylpyridine (1a) and (E)-N-benzylidene-4-methylbenzenesulfonamide [22], 2-bromo-6-methylpyridine and (E)-styrylboronic acid [37], as well as 2-methylpyridine and phenylmethanamine [38]. Most recently

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• 1a (1 mg). To the dried water-soluble phase were added pyridine (0.5 mL) and ʟ-cysteine methyl ester hydrochloride (0.5 mg), and the reaction mixture was stirred at 60 °C for 1 h. Then, o-tolyl isothiocyanate (0.1 mL) was added and the mixture stirred at 60 °C for another 1 h. The reaction mixture

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• . Experimental General procedure: An oven-dried narrow-mouth FEP tube (Nalgene®, 10.0 mL) containing a magnetic stirring bar was charged with substrate 1 (0.3 mmol), FLUOLEAD® (225.3 mg, 0.9 mmol, 3.0 equiv) and the nHF·pyridine complex (HF 70%, pyridine 30%, 1.5 mmol, 5.0 equiv, neat). The tube was tightly

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• , entry 9). With the optimal conditions in hand, the reaction was exemplified with various other electrophiles (Scheme 2). The reaction gave generally good results with reactive electrophiles such as benzylic, allylic or propargylic ones (3a–k). Noteworthy, in the reaction with 2-(bromomethyl)pyridine (2g

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• , Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium 10.3762/bjoc.16.243 Abstract N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

• formation of tar-like products. 2,5-Bis(N-sulfonylamidino)pyridines Bis(thioamide) 1p containing a pyridine ring was found to react with sulfonyl azides 2a,c–f either in boiling propanol or in the absence of a solvent to form compounds 3aj–an bearing two N-sulfonyl amidine fragments connected to a pyridine

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• pyrrole-3-carboxamides. In the presence of 1.2 equiv of KI, a polysubstituted pyrazolo[3,4-b]pyridine derivative was also successfully synthesized. Keywords: acid catalyst; [1 + 2 + 2] annulation; KI; pyrazolo[3,4-b]pyridine; pyrroles; Introduction Among nitrogen-containing heterocycles, pyrroles have

• synthesis, we also observed an unexpected reaction in which the pyrazolo[3,4-b]pyridine scaffold was constructed under analogous conditions. As shown in Scheme 6, In the presence of a catalytic amount of AlCl3 and 1.2 equiv of KI, 3-methyl-1-phenyl-1H-pyrazol-5-amine (1b) reacted smoothly with 2a and 3a

• , affording the polysubstituted pyrazolo[3,4-b]pyridine 5a in 53% yield. The formation of an imine intermediate V may be involved in the reaction mechanism, and the enamine form of V contained two nucleophilic sites to react with a molecule of 3a, which generated the intermediate VI. Finally, VI underwent an

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• imidazo[1,5-a]pyridine core is also considered to be one of the privileged pharmacophoric scaffolds and can be found in many biologically active compounds, for example, the potent antitumor agent C 1311 inhibiting topoisomerase II [4][5][6][7][8][9] or pirmagrel, a cytotoxic immunosuppressant and DNA

• development of efficient synthetic methods to access imidazo[1,5-a]pyridines, with more than 120,000 individual compounds prepared to date. Most synthetic approaches rely on various cyclocondensations of nucleophilic (2-aminomethyl)pyridine precursors, introducing a new five-membered ring. Typically

• highly important imidazo[1,5-a]pyridines. It was imagined that the initial nucleophilic attack of the 2-(aminomethyl)pyridine (12) on the nitronate 2 would provide an amidinium species 13, which is very well suited for a 5-exo-trig cyclization involving the masked imine moiety of the pyridine ring

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• significant damage of the Cu species. The pyridine-containing moiety, such as arylpyridines, widely exist in natural products, pharmaceutical agents and functional materials [34][35][36][37]. Traditional methods for synthesizing pyridine-containing derivatives include condensation reactions, cross-coupling

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• the mannose analogue 14 in higher yield and using pyridine·1HF as reagent (pyridine·9HF with 120 equivalents of pyridine) allowed only poor conversion of starting material. Finally, performing the reaction in neat Et3N·3HF (no additive) provided almost exclusively talose analogue 12 with no

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• aptamer that adopts a guanine quadruplex structure was modified by four pyridine ligands [22]. The addition of Cu(II) or Ni(II) ions leads to the formation of a square-planar complex that reduces the affinity of the modified aptamer to its target protein. To the best of our knowledge, there is no

• , and Merck. Dry pyridine was purchased from Acros Organics. Dichloromethane was distilled and dried over molecular sieves. Milli-Q water was used to prepare solutions and buffers. The silica gel used for product purification (Geduran® Si60, 40–63 µm) was purchased from Merck. The DMT- and

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• derivative 8 with free 3’-OH group, which then can be converted to the phosphoramidite prior to use at the RNA synthesizer. Protocols for selective 2’-O-silylation are available [29][30][31], however, the standard procedure using AgNO3, pyridine and TBDMS-Cl, in this case led to unexpected results. The

• adenosine [33][34]. The 3′,5′-O-di-tert-butylsilyl protecting group, in contrast to the Markiewicz group (1,1,3,3-tetraisopropyldisiloxane) can be selectively removed with HF-pyridine [35][36]. It was used for the iodination of cytosine residues previously [37], but to the best of our knowledge never for

• without changing the reaction conditions used for the previous iodination of 2, resulting in the product 11 with a yield of 83%. The protection of the exocyclic amine lead to nucleoside intermediate 12, from which the 3′,5′-O-di-tert-butylsilyl group was selectively removed with HF-pyridine without

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

• -glucopyranose as an intermediate. The latter could be used in the next step upon concentration of the reaction mixture under reduced pressure (Scheme 1) [20]. The intermediate was then treated with sodium methoxide in the presence of pyridine in order to generate the Černý epoxide 2 in a 73% yield over two

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• ) and ithomiolide A (3). Biosynthetic formation of hedycaryol (7) and α-elemol (8). Synthesis of isoprenyl 3-acetoxyoctadecanoate (11). a) IBX, EtOAc, 60 °C, 3.15 h, 99%; b) SnCl2, CH2Cl2, rt, 70%; c) NaBH4, 12 h, 98%; d) SnOBu2, 140°C, 36 h, 78%; e) Ac2O, pyridine, DMAP, CH2Cl2, 12 h rt, 67%. a) 48

• % HBraq, toluene, 24 h, 110 °C, 79%; b) IBX, EtOAc, 60 °C, 3.15 h, 90%; c) C5H11PPh3Br, LDA, THF, −78 °C, 12 h, 84%; d) i) Mg, 21, THF, ii) (S)-22, Cu(I)I, THF, –30 °C, 12 h, 79%; e) SnOBu2, 140°C, 36 h, 65%; f) Ac2O, pyridine, DMAP, CH2Cl2, 12 h rt, 74%. Proposed biosynthetic pathway of fatty acids

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• groups of the hexafluoroisopropyl fragment with the neighboring hydrogen atom of the pyridine ring. A similar phenomenon was previously observed for N-(hexafluoroisopropyl)benzimidazole [17]. 5-Azabenzimidazole (4) reacted similarly with tetrakis(trifluoromethyl)-1,3-dithietane (1), which also resulted

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• (acetylide)platinum(II) complex [Pt(L1)2(PBu3)2] as a linear metalloligand. The reaction of this metalloligand with iron(II) cations and pyridine-2-carbaldehyde according to the subcomponent self-assembly approach yielded decanuclear heterobimetallic tetrahedron [Fe4Pt6(L2)12](OTf)8. Thus, combination of

• trans-[Pt(PBu3)2Cl2] (2). The aniline moieties in 3 were further transformed into chelating pyridylimine binding sites in the following subcomponent self-assembly process when six equivalents of metalloligand 3 were reacted with twelve equivalents of pyridine-2-carbaldehyde and four equivalents of iron

• diameter from the DOSY experiment (dh = 33 Å). Conclusion In summary, we presented the self-assembly of a large decanuclear heterobimetallic tetrahedron that was readily obtained in a stepwise manner. The linear metalloligand 3 facilitated the formation of tetrahedral cages, when combined with pyridine-2

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• μM) and 2 (IC50 > 1000 μM). The attempted synthesis of 6 (a diastereoisomer of 2) via a one-step 1,2-difluorination reaction [24]. Py = pyridine; m-CPBA = m-chloroperbenzoic acid, DCM = dichloromethane. The attempted synthesis of 2 via a stepwise fluorination approach (ether series). THF

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• shown that the spin switching efficiency is strongly dependent on the solvent and on the substituent at the 4-position of the pyridine unit. We now introduced thiol, disulfide, thioethers, nitrile and carboxylic acid groups and investigated their spin switching efficiency. Keywords: azopyridines; Ni(II

• the switchable ligand). This approach has been dubbed “record player” design for obvious reasons (Figure 1a). The Ni-porphyrin (“disk”) is low-spin if the azo-aryl unit (“tone arm”) is in trans configuration. Upon switching to the bent cis configuration, the lone pair of the pyridine (or imidazole

• substituents at the pyridine or imidazole part) to increase the Ni–ligand coordination strength. Strong coordination in turn improves the performance of the spin switch, namely the conversion rate to the cis isomer, the conversion rate to the high-spin state, as well as the thermal stability of the high-spin

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• sources (e.g., Et3N⋅3HF and HF–pyridine) and halonium ion sources (e.g., N-halosuccinimides) are relatively cheap and easily available, halofluorination might be an economic way to obtain vicinal halofluorides that can be transformed further in various ways thanks to the different leaving group abilities

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• starting material can be found, is to trace to a non-renewable starting material (i) that is a first generation feedstock such as coal, crude oil, or ores from the earth’s crust; or (ii) whose molecular weight is less than 80 g/mol corresponding to benzene or pyridine starting materials. The third option

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• NMR spectrum supports the pyridinium structure of 3 as the aromatic peaks shifted downfield by 0.6–1.4 ppm relative to the chemical shifts in pyridine 22. The IR spectrum supports the structure of 3 as strong peaks for both an azide asymmetric stretch (ν 2102 cm−1) and a PF6− stretching vibration (ν

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• pyridine (as a base and ligand), and 1 equiv of copper acetate at room temperature (see Table 1, entry 1). The product yield decreased slightly to 80% with 1 equiv of pyridine (Table 1, entry 2) and dropped dramatically to below 5% under pyridine-free conditions (Table 1, entry 3). With decreased amounts

• of both pyridine and copper acetate (0.4 and 0.2 equiv, respectively), the yield was reduced insignificantly to 81% suggesting, however, the catalytic nature of the conversion (Table 1, entry 4). Boiling the reaction mixture for 10 h led to a markedly reduced yield of 45% (Table 1, entry 5). The

• replacement of pyridine by other organic bases/ligands (4-DMAP, 2,2’-bipy, Et3N, TMEDA, 8-hydroxyquinoline) resulted in poorer yields of the target product in all cases (Table 1, entries 6–10). The use of copper(II) fluoride (in contrast to triflate) instead of acetate had practically no effect on the

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• precursors for the installation of fluorine atoms using appropriate fluorinating agents such as (difluoroiodo)benzene derivatives or elemental fluorine. In the second step, when they used para-iodotoluene difluoride the reaction conversion was very low, therefore, when using Olah’s reagent (pyridine

• crystallographic analysis. To further advance the sumanene chemistry, in 2018, Sakurai and co-workers reported diosmylation and also synthesized the phenylboronate ester 121 of sumanene (2, Scheme 29) [24]. The osmylation of sumanene was carried out by OsO4 in pyridine to yield the diadduct 120. Although, they

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• switch the catalytic activity of the dimethylaminopyridine (DMAP) unit. DMAP is a known catalyst in the nitroaldol (Henry) reaction. Upon coordination to the Ni2+ ion, the basicity of the pyridine lone pair is attenuated and hence the catalytic activity is reduced. Decoordination restores the catalytic

• ][19][20][21][22][23][24][25][26]. In the present study, the basicity change linked to the coordination/decoordination process is explored. If the azo substituent is in cis configuration, the lone pair of the pyridine unit coordinates to the central Ni2+ ion, reducing the nucleophilic power and the

• basicity of the pyridine (Figure 1). In the trans configuration intramolecular coordination is prohibited and nucleophilicity and basicity are restored. Reversible switching between the two states is achieved by irradiation with green (trans→cis) and violet (cis→trans) light. The title compound of this

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• procedure was confirmed by a Kaiser test. Several cycles of deprotection, coupling, and washing procedures were repeated until the desired peptide was obtained. The N-terminus of the peptide was acetylated by adding 10 mL of a mixture of acetic anhydride/pyridine/DMF 1:2:3 to the peptidyl resin at room

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• ion-pair interaction. For example, the replacement of the pyrrole core to pyridine in 8 or to furan results in a much weaker binding because of the repulsion force between the lone pair on the heteroatom and the oxoanion. The superior oxoanion binding of the Schmuck cation makes GCP-based peptides