Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• prepared from ʟ-tartaric acid and ethanol. THF was freshly distilled after refluxing with Na, while SOCl2, pyridine, PCl3, and I2 were purchased and used directly. Commercially available starting materials were used without further purification if not specified otherwise. Chiral phosphoric acid 3 was

• (2R,3R)-6 (6.1 g, 13 mmol) and added dropwise to the mixture. After the addition, the mixture was stirred at 0 °C for 1 h, warmed to rt, and stirred for an additional 0.5 h. Then, 1.5 mL of H2O were added, followed by 10.9 g of I2, and 7.1 mL of pyridine and the mixture stirred for another 1 h

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• by GlfT2. Reagents and conditions: a) 1. (BnO)2P-NMe2, 1H-tetrazole, 0 °C→rt, 1 h, 2. m-CPBA, 0 °C→rt, 1.5‒2 h; b) H2, 10% Pd/C, MeOH, rt, 3‒4 h. Reagents and conditions: a) PivCl, pyridine, CH2Cl2, rt, overnight; b) BnBr, NaOH, TBAB, THF, reflux, 3 h. Reagents and conditions: a) EtSH, BF3∙OEt2

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• merging C–H activation with photoredox catalysis to allow in situ reoxidation of the metal catalyst. In 2015, a procedure combining ruthenium C–H activation of phenols derivatives bearing a pyridine moiety as DG and photoredox catalysis was disclosed (Figure 9) [75]. This ortho-olefination was performed

• the C–H cleavage step slightly, yet significantly absorbed light in the relevant blue region. This absorption was believed to trigger the overall catalytic cycle at room temperature as no product formation was observed in the dark. The mechanistic scenario thus foresees an initial pyridine-directed

• borylation under mild reaction conditions, thus delivering, after oxidation of the crude reaction mixture with Oxone, a large panel of the corresponding hydroxylated pyridine products. From the mechanistic point of view, this reaction is expected to differ from the previously described Ru-catalyzed meta

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• combination of DABCO and DMSO also afforded the desired product via a clean reaction within 20 min, although only 60% yield of the product was obtained (Table 1, entry 10). This promising result using DABCO encouraged us to explore other amines like DBU, ʟ-proline, pyridine, DMAP, and pyrrolidine as an

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• directing the reaction exclusively towards indole formation by reacting the diketone with appropriate substrates, combining a primary amine with a tertiary amine or a pyridine separated by several spacer arms (Scheme 6). Under these conditions, the functional indoles 6h–l were obtained exclusively in 45–55

• % yield. We assume that the tertiary amine would interact with the protonated intermediate, and thus promoting the 1,2-addition (Scheme 6). However, for the pyridine substituent (compounds 6k and 6l), another intermediate may be involved as the shape of this diamine does not allow enough flexibility to

• % yield (Scheme 7). Here again, the amount of indolone was found to be almost constant, whatever the amine involved was, suggesting that the reaction is not dependent on the nature of the amine. It is worth to notice that, for a substrate combining a primary amine with a pyridine separated by a spacer arm

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products. Keywords: microwave irradiation; N2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine

• 5-aminotetrazole (3) in pyridine under controlled microwave heating (Scheme 2). Results and Discussion With the initial aim of optimizing the reaction conditions, we began our study by reacting equimolar amounts of cyanamide 1, aromatic aldehydes 2, and 5-aminotetrazole (3) in pyridine and the

• experimental conditions and the results revealed that performing the reaction in dioxane, CH3CN, THF, or catalyst-free ethanol resulted in no product formation. However, the same products were obtained with lower yields (≈60%) when performing the reaction under conventional heating utilizing pyridine as the

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• ) in pyridine (2 mL) was added CH3COSH (1 mL, 14.2 mmol) and the reaction mixture was stirred at room temperature for 12 h. The solvents were removed under reduced pressure and the product was passed through a short pad of SiO2 using hexane/EtOAc 2:1 to give the N-acetylated product. To a solution of

• the product in CH3CN (10 mL) was added HClO4-SiO4 (50 mg) and the mixture was allowed to stir at room temperature for 15 min. Then, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. To a solution of the diol in CH2Cl2 (5 mL) were added pyridine (100 μL, 1.24

• synthetic intermediates. Stepwise stereoselective synthesis of tetrasaccharide 1. Reagents and conditions: (a) NIS, HClO4-SiO2, CH2Cl2, MS 4 Å, −15 °C, 30 min, then 20 °C, 30 min, 73% for compound 5, 70% for compound 6, and 74% for compound 7; (b) CH3COSH, pyridine, rt, 16 h; (c) HClO4-SiO2, CH3CN, rt, 15

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• substituents, electron-neutral and electron-rich rings with several substitution patterns performed well. However, pyridine-based 48j resulted in a low yield. Noteworthy, the PKR of chiral enynes 48 led to a bridgehead quaternary stereocenter containing a C–F bond in a single step. Besides the intrinsic

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• fluorinating reagents [44][45]. Developments by Hammond and Xu validated N-pyridine oxides as terminal oxidants to substitute Selectfluor® for the cationic Au(I)/Au(III) cycle, thereby enabling high functional group tolerance [46][47][48][49]. Inspired by these and other selected advances [50][51], in metal

• (50% yield), ground Oxone® or N-pyridine oxide proved to be ineffective (Table 1, entries 9–11). Increasing the reaction temperature to 50 °C led to the same outcome as at ambient temperature (64% yield, Table 1, entry 12). Finally, the control reactions in the absence of catalyst, oxidant and HF

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• evaluated (Scheme 1). Results and Discussion Chemistry The unsubstituted DHBER was prepared by treating BER with 2.5 equivalents of NaBH4 in pyridine at room temperature [66][67], and employed in the reaction with α-bromohydrazone 1a chosen as the representative model, to determine the optimal reaction

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• -donating functional groups. Substrates containing pyridine, furan, and thiophene as heterocyclic fragments were also successfully converted into the corresponding alcohols 4. However, in the reaction of the enol ether derived from 2-acetyl-N-methylpyrrole, ketone 3p did not undergo reduction with sodium

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• bipyridyl units have been designed to immobilise transition metal complexes through coordinate bonding for the oxidative coupling of amines [138]. [Ru(bpy)3]2+ units were synthesised with ethynyl groups para-substituted to the nitrogen heteroatom on four of the six pyridine rings. The ethynyl groups were

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• nucleophilicity of pyridine compared with the tertiary alkylamine present in compound 12 [45][46] may be responsible for the lower vulnerability of 9 towards alkylation. Another approach to circumvent the formation of N-alkylation products was based on the use of the more sterically hindered diisopropyl

• this study, we took a closer look at the reactivity upon exposure to BTMS of two types of carboxyester groups, the acid-labile tert-butyl and the relatively stable ethyl esters. For this we chose triethyl phosphonoacetate (8a), tert-butyl phosphonoacetate (8b) and its pyridine-3-ylmethyl analogs 9a,e

• pyridine (1 or 2 equiv) as scavengers. Although the reaction slowed down, still a significant cleavage of the tert-butyl ester bond was detected within 24 h (Table 4, entries 4 and 5). This observation might imply that this reaction was similar to the one between carboxyesters and ITMS, and proceeded via a

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• radical 48, the protonated pyridine 47, and bromide. The following addition of alkenes to the generated difluoroamide radical 48 gives the intermediate 49. Finally, the desired difluoroalkylation product 50 is produced by a subsequent HAT from thiophenol to the intermediate 49, and the thiyl radical 43

• intermediate 51 to the phenyl thiyl radical 43 yields the intermediate 49, thiophenol, the protonated pyridine 47, and bromide. Finally, HAT from the thiophenol to the intermediate 49 gives the difluoroalkylation product 50. Alkene functionalization reactions The olefin hydration is an important method to

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• -methylacrylnitrile (251a) and methyl 2-methylacrylate (251b), respectively, affording the corresponding spirothietanes 253 regiospecifically in 67–99% yields for acridine-9-thione 249b and its N-methyl derivative 249a. However, for pyridine-4(1H)-thione (250), the generated thietane intermediates 254 underwent ring

• chloromethylthiirane (epithiochlorohydrin, 398a), with hard and weak nucleophiles [105][106][107][108][109], including phenoxides [105], carboxylates and dicarboxylates [106][107], potassium cyanide, sodium azide, hydroxylamine, trifluoromethanesulfonamide, and pyridine [108]. However, the method could only applied to

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• the C-3 carbon atom. The obtained products were benzoylated with benzoyl chloride/pyridine in the presence of DMAP to give the fully benzoylated isoxazolidine-4,5-diols 6a and 6b, which were subsequently treated with Et3SiH (3 equiv) and TMSOTf (2 equiv) in anhydrous CH2Cl2 at room temperature for 2 h

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• poor yields. Other synthetically useful substituents, including cyano, nitro, phenylsulphonyl, (pinacolato)boron, and alkyl groups could be tolerated in the reaction (24–30), leading to a yield range between 26 and 65%. The trifluoromethoxylation of pyridine, pyrimidine, and thiophene derivatives also

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• % yields. The substituent groups R2 including electron-donating (Me, OMe, -OCH2O) or -withdrawing groups (CF3, Cl) on the benzene ring have a little effect on the yield of products 9h–l. Product 9m bearing a naphthyl group was produced in 70% yield. Product 9n containing a pyridine ring was not obtained

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• N-containing functional groups on the surface of ammonia treated activated carbon samples such as bands of N–H stretching vibrations (3376–3294 cm−1), cyclic amides (1665–1641 cm−1), nitriles (2251–2265 cm−1) and pyridine-like functionalities (1334–1330 cm−1). Simultaneously, a diminished band at

• amines, imines, amides, pyridine nitrogen and pyrrole nitrogen or as oxidized nitrogen species, e.g., pyridine-N-oxides [10]. Díaz-Terán et al. examined the surface of the samples (surface groups, chemical state of the elements, metal content and distribution) during the activation process of

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• intermolecular alkene 1,2-aminopyridylation to give the difunctionalized products 32.3 (Scheme 32) [148]. Eosin Y (OD13) was an efficient dye for the SET reduction of the N-aminopyridinium salts, which act as bifunctional reagents as the released pyridine later added to the olefin 32.1. The generation of amidyl

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• some reported to act as antioxidants and show activities that are medicinally relevant; hence, the development of efficient methods for their synthesis is an important objective. Herein, a simple method for the synthesis of selenides and diselenides bearing imidazo[1,2-a]pyridine rings and their

• anticancer activity are described. The double C–H selenation of imidazo[1,2-a]pyridine with Se powder was catalyzed by CuI (10 mol %) ligated with 1,10-phenanthroline (10 mol %) at 130 °C under aerobic conditions. The selenides or diselenides were prepared almost selectively using selenium powder in an

• appropriate quantity under otherwise identical reaction conditions. The prepared selenides and diselenides bearing two imidazo[1,2-a]pyridine rings were all novel compounds. Among the prepared diselenides and selenides that exhibited cytotoxicity against cancer cells, bis[2-(4-methoxyphenyl)imidazo[1,2-a

Synthesis of novel multifunctional carbazole-based molecules and their thermal, electrochemical and optical properties

• Nuray Altinolcek,
• Ahmet Battal,
• Mustafa Tavasli,
• William J. Peveler,
• Holly A. Yu and
• Peter J. Skabara

Beilstein J. Org. Chem. 2020, 16, 1066–1074, doi:10.3762/bjoc.16.93

• multifunctionalisation [31]. In this work, we designed two novel 2-(N-hexylcarbazol-3’-yl)-4/5-formylpyridine compounds (7a and 7b), where 4/5-pyridinecarboxyaldehyde was attached to the 3-position of carbazole via the 2-position of the pyridine ring. These two compounds (7a and 7b) can be used in OLEDs, solar cells and

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• oxazoles (17 examples, up to 87% yield) were difluoromethylated but a variety of other heteroarenes turned out to be suitable such as pyridine, imidazole, benzo[d]thiazole, benzo[b]thiophene, benzo[d]oxazole, thiazole and thiophene derivatives (Scheme 6). Copper-based CF2FG-containing reagents Besides the

• dealt with the copper-mediated perfluororalkyaltion of (hetero)aryl bromides using the previously developed PhenCuRF [69]. Although the trifluoromethylation reaction was mainly studied, the methodology was efficiently extended to the pentafluoroethylation of various heteroarenes such as pyridine

• ). The reaction was efficient (65 examples, up to 97% yield), showed a good functional group tolerance (i.e., cyano, ester, ketone) and even heteroarenes such as pyridine, quinoline and quinoxaline were functionalized with the four fluorinated moieties (Scheme 17). In situ-generated copper-based

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• synthesis from ethyl trifluoropyruvate hemiketal The reaction of ethyl trifluoropyruvate hemiketal 130 with thionyl chloride in pyridine afforded the chlorinated derivative 131, which upon treatment with zinc powder in DMF, afforded the dihalogenated olefin 132. The substitution of one fluorine atom in 132

• derivatives by HF/Py The ring opening reaction of aziridines 138a,b by treatment with hydrogen fluoride in pyridine afforded 3-fluorophenylalanine esters 139a,b. The subsequent enzymatic hydrolysis of esters 139a,b gave the threo-isomer 136 in an enantiomerically pure form [68][69] (Scheme 31). On the other

• diastereoisomeric purity (dr > 99:1) (Scheme 38). 2.9. Direct fluorination of β-methylene C(sp3)−H The direct fluorination of β-methylene C(sp3)−H bonds of Phe derivatives 157a–v having installed the bidentate auxiliary, 2-(pyridine-2-yl)isopropylamine (PIP-amine) 158, was attempted using Selectfluor in the

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• , and Grignard reagents. Review Copper-catalysed C–C bond-forming reactions at the heterocycle The direct synthesis of chiral heterocyclic molecules from pyridine, quinolone, or indole derivatives is advantageous due to the abundance of such building blocks. Unfortunately, establishing catalytic

• alkenylpyridines in the substrate scope. The reason for this was the markedly lower reactivity of alkenylpyridines towards nucleophilic addition as compared to other alkenylheteroarenes. For the same reason, the synthesis of chiral pyridine derivatives has always been considered a challenge in organic chemistry

• conditions that allowed highly enantioselective ACAs of Grignard reagents to alkenylpyridines (Scheme 15) [46]. Using the optimised conditions (Cu/L7/TMSOTf), a large variety of pyridine-based chiral compounds was synthesized. Apart from allowing the introduction of different linear, branched, cyclic, and