On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• also mentioned that this heterocycle appears to be under-represented in the DrugBank database (in comparison with pyridine-containing substances) plausibly because of a lesser “availability of pyrazine fragments in vendors”. For chemists, this statement could be translated as “fragments” far more

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -tert-butyl-4-hydroxyphenyl)-2-phenoxy-1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxide (252) as byproduct. The yield of 6-amino-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-phenoxy-1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxide (252) was improved to 35% when the reaction was conducted in refluxing

• + 1] Annulations have been mainly utilized in the construction of the 1,2-azaphospholidine ring, while the [3 + 2] annulation has been seldomly used in the synthesis of pyridine-fused 1,2-azaphospholidine 2-oxide only. Few asymmetric synthetic methods have been developed to date. Thus, highly

• ]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-phenylphosphinamides with electron-withdrawing ethenes via the rhodium-catalyzed oxidative coupling and subsequent intramolecular aza-Michael addition. Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides. Funding The

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• groups in many biologically active substances and pharmaceuticals, such as zolpidem, alpidem, and GSK812397 [1][2][3]. Therefore, the development of multiple chemical modification methods, at the 3-position of the imidazo[1,2-a]pyridine skeleton, for the synthesis of 3-substituted-imidazo[1,2-a]pyridines

• with an imidazo[1,2-a]pyridine ring, this study focused on the Cu-catalyzed one-pot C(sp2)–Se and C(sp)–Se bond formation for the synthesis of novel alkynyl imidazopyridinyl selenides using Se powder, 2-arylimidazo[1,2-a]pyridines, and terminal alkynes. Results and Discussion Synthesis of alkynyl

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• . In 2002, Monkman reported the addition of camphor sulfonic acid (CSA) to the fluorescent polymer poly{2,5-pyridylene-co-1,4-[2,5-bis(2-ethylhexyloxy)]phenylene} (compound 1 in Figure 2) containing pyridine groups led to the protonation effect [26]. CSA has strong acidity and low volatility, which is

• feasible to be bound with pyridine groups. As shown in Figure 3a, the protonation by CSA resulted in a significant red-shift in the photoluminescence (PL) spectrum, which was similar to the cases caused by other Lewis acids such as methanesulfonic acid (MSA) and dichloracetic acid (DCA). Wang et al. used

• both quinoline and pyridine as N-containing heterocycles rich in electrons, which are the key structural factors leading to acid discoloration. At the same time, Kappaun et al. synthesized a series of conjugated alternating and statistical copolymers (poly[2,7-(9,9-dihexylfluorenyl)-alt-(2,6-pyridinyl

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• . Further conversion by treatment with PPh3, iodine, pyridine, and water [38] gave access to (R)- and (S)-2-methyllinalool (6a and 6b). The materials were subsequently converted into the diphosphates using triethylammonium phosphate and trichloroacetonitrile [39] (Scheme 2). Conversion of enantiomerically

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• -triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Keywords: isoxazole; methyl nicotinate; molybdenum hexacarbonyl; 4-pyridone; ring expansion; Introduction Pyridine moieties are present in many natural products, drugs, pesticides and industrial materials. Pyridine fragments are used in drugs

• due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well

• not detected. It is most probable that, in addition to the reductive opening of isoxazole, Mo(CO)6 catalyzes the cyclization of enaminone 3g to pyridine 2g [14]. In the absence of such catalysis, the unstable enaminone intermediate undergoes deacylation and decomposes through other destructive

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• most suitable agent for synthesising isocyanides when combined with a basic milieu. Among the immense variety of compounds that can be employed as bases, only a few are reported to catalyse such a process: pyridine [31] and triethylamine [32] are the most representative ones. Their reactivity can be

• , pyridine handling is associated with many risks, mainly concerning human health [36]. Consequently, our idea was to substitute pyridine with N-methylimidazole because their basicity and physical state are analogous. When the reactions between the formamide and different equivalents (from 1 to 6) of N

• -methylimidazole were carried out, the outcomes were not as good as those already documented with pyridine in the literature. Possible explanations for this phenomenon are either a different electronic distribution between the two heterocycles or the absence of intermolecular interactions caused by the solvent

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• , since a variety of heteroleptic aggregation protocols have been developed by Schmittel [37] (for copper(I), zinc(II), cadmium(II), mercury(II) ions) and Yoshizawa/Fujita [38] (for palladium(II) ion) that involve pyridine-derived ligands. Highly innovative are the approaches for terpyridine-based

• PYridine and Phenanthroline complexes [85][86]), HETPHEN (HETeroleptic bisPHENanthroline complexes [87]) and HETTAP (HETeroleptic Terpyridine And Phenanthroline complexes [88]) interactions (Figure 12). Due to the different amount of donor atoms about the metal ion, the binding strength will decrease in

• + was developed on the basis of two complexation events, i.e., the zinc(II) HETTAP (log β = 14, log K1 ≥ 6) and Npy → ZnPor (log K = 4.45) binding motifs (Figure 12) [89]. Due to the design of 52, the pyridine terminal oscillates between the two degenerate zinc porphyrin (ZnPor) stations of 53 at k298

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• , Japan Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7, Huis Ten Bosch, Sasebo 859-3298, Japan Graduate School of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8131, Japan 10.3762/bjoc.18.60 Abstract Novel pyridine-based fluorescing compounds, viz

• have been reported [7][8][9][10]. Because the aggregated state of AIEE-based compounds is affected by the external environment, these compounds have found use in clinical applications as chemical sensors or fluorescent probes [7][8][9][10]. Pyridine is a nitrogen-containing heterocyclic compound found

• in many bioactive substances and medicines as one of the basic core skeletons [11][12]. In addition, pyridine is an essential skeleton for fluorescent compounds, and fluorescence can be enhanced by optimizing the internal charge transfer (ICT) state of pyridine by introducing electron-donating or

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• hydrolysis, was dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixture was stirred at 60 °C for 1 h. Then O-tolyl isothiocyanate (30 μL) was added and stirred at 60 °C for 1 h. The reaction mixture was analyzed without purification by LC–MS analysis

• using GC–MS. Monosaccharides (1, 0.4 mg; 2, 0.3 mg; 3, 0.4 mg; 4, 0.4 mg), obtained by hydrolysis, were dissolved in pyridine (0.5 mL), then ʟ-cysteine methyl ester hydrochloride (2 mg) was added. The reaction mixtures were then stirred at 60 °C for 2 h. After adding 1-trimethylsilylimidazole (0.1 mL

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• , Ph3P, Ac2O, reflux. aReported yields are 1H NMR yields. bIsolated yield. i) LiHMDS, MeI, THF, −78 °C. i) a) NaOH, MeOH/H2O, rt, Amberlyst 15 [H+], b) AcOH 70% aq, reflux, 2 h; ii) a) EtOCOCl, pyridine, b) Et3N, CH2Cl2; iii) (Ph3P)4Pd, BSA, THF. i) Lawesson’s reagent, HMDO, toluene, MW irradiation (120

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• )-38, featuring the BINOL unit on the axle, does not allow for higher stereoselectivities (19% ee), but interestingly gives the other product enantiomer as the main product (see Figure 9). In 2016, Takata and co-workers reported a pyridine-based rotaxane catalyst for the O-acylative asymmetric

• pyridine axle, followed by ion exchange, gave rise to the cationic rotaxanes 64a/b in 23/37% overall yield, both of which feature four iodotriazoles as XB donors. While rotaxane (S)-64a only possesses the BINOL unit as a stereogenic element, the system (S,S,S)-64b features two additional chiral centers on

• featuring BINOL-based [2]rotaxane side chains. Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38. Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R)-38. Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42. The asymmetric

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• three component catalyst system consisting of iron(III) chloride, pyridine-2,6-dicarboxylic acid (H2Pydic), and benzylamine (1:1:2.2) for the oxidation of 16 with H2O2, in tert-amyl alcohol (TAA), allowed to obtain 10 in 44% yield (Table 1, entry 9) [55]. Subsequently, Kulkarni’s group evaluated the

• H2O2 and acetic acid as oxidant. Additionally, the selectivity of this process was 99% (Table 2, entry 6). Beller et al. developed another approach using H2O2 as oxidizing agent in combination with a three component catalyst system consisting of FeCl3·6H2O, pyridine-2,6-dicarboxylic acid (H2Pydic), and

• steps whose main difficulties are the separation of pyridine byproducts and inorganic phosphate (Scheme 20). Kulkarni and co-workers reported a method for menadione reduction mediated by 5,6-O-isopropylidene-ʟ-ascorbic acid (70, R = H) under UV light irradiation [120]. Initial studies were carried out

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• iron complex B is formed by the oxidative addition of the iron catalyst to the pyridine derivative. Intermediate Fe species were obtained by transmetallation and finally a new carbon–carbon bond is formed by reductive elimination (Scheme 19). This method provided access to a diverse range of 7

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• aldehydes (Scheme 2) and subjected to the optimised flow conditions (Scheme 3). This resulted in full conversion of the substrate in all cases. Both thiophene and pyridine-containing substrates were well tolerated, with slightly higher yields observed in the case of the more electron-deficient CF3

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• and sugar, respectively. The aqueous residue was concentrated to dryness under N2. The aqueous residue, ᴅ-glucose (2 mg), and ᴅ-xylose standard (2 mg) were separately dissolved in 0.5 mL anhydrous pyridine, and ʟ-cysteine methyl ester hydrochloride (2.0 mg) was then added. Each reaction mixture was

• key correlations observed in the 1H-1H COSY (bold bonds), HMBC (blue) correlations of 1 (recorded in pyridine-d5, 600 MHz). The key correlations observed in the 1H-1H COSY (bold bonds), HMBC (blue), ROESY (red) of 1 (recorded in DMSO-d6, 800 MHz). 1H and 13C NMR Spectroscopic Data for 1 (δ in ppm, J

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• reactivity of pyridine derivatives with NFSI, which are known to generate phenylsulfonyl fluoride via a transient generation of N-sulfonylpyridinium salts [37]. Analysis by 19F NMR spectroscopy of the crude reaction mixture of 3b and NFSI revealed the presence of PhSO2F (Scheme 3d), thus confirming the

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The

• pyridine to afford dimesylated nucleosides 16a,b in 93 and 94% yields, respectively. The reaction of nucleosides 16a,b with NaOH in dioxane/water (1:1) underwent a cascade reaction pathway to form 9a,b in 82 and 84% yields, respectively (Scheme 4). The overall yields for the synthesis of nucleosides 9a,b

• regioselective protection of the primary hydroxy group of diol 17 using TBDPS-Cl in pyridine at room temperature afforded TBDPS-protected furanoside 18, which on acetolysis using AcOH/Ac2O/H2SO4 (100:10:0.1) afforded the anomeric mixture of coupling sugar 19a,b in 80% yield. The Vorbrüggen coupling [29] of

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• HCl(g) in MeOH (Scheme 1). N-Boc protection of cis-amino ester 3 with (Boc)2O in pyridine and 4-(dimethylamino)pyridine (DMAP) gave N-Boc-amino ester 4 (yield 95%). The 1H and 13C NMR spectroscopic data of 4 were in agreement with the proposed structure. Treatment of 4 with OsO4/NMO gave the expected

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• and reported that they were unable to obtain 4-arylamino-1,2-naphthoquinones from β-NQSNa but that these derivatives can be readily prepared from 4-ethoxy-1,2-naphthoquinone. Similarly, Yano and co-workers [72] studied the tautomeric equilibrium of 4-arylamino-1,2-naphthoquinones in DMSO-d6, pyridine

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

• %; (c) 12WO3·H3PO4×H2O, H2O2 (35 wt % in H2O), pyridine, ethyl acetate, rt, 48 h, 70%; (d) BF3·OEt2, CH2Cl2, 0 °C, 15 min, 69%; (e) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h, (±)-2, 71%; (f) H2 (1 atm), Pd(OH)2/C (5 wt %), MeOH, rt, 2 h; then formaldehyde (37 wt % in H2O), H2 (1 atm), Pd(OH)2/C (5

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• provided the corresponding carboxylic acid, and further oxidative decarboxylation with lead tetraacetate and pyridine provided oxathiolane 20. Chu and co-workers [41][42] further established a more proficient system for the synthesis of (+)-BCH-189 (1a) from 1,6-thioanhydro-ᴅ-galactose (3d, Scheme 4

• reaction of benzoyl chloride in pyridine to protect the hydroxy group, which results in a high yield. The isopropylidene group was selectively deprotected using 10% HCl, followed by oxidative breakage of the carbon–carbon bond of the resulting diol using sodium periodate. Further reduction of the aldehyde

• afforded the thiol compound 3nb. Further treatment of the thiol 3nb with methyl glyoxylate in dichloromethane solvent along with molecular sieves (4 Å), followed by in situ acetylation using Ac2O, pyridine, and catalytic 4-(N,N-dimethylamino)pyridine (DMAP) provided compound 37. The second route involves

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• obtained via TBHP-mediated cyclization of 23 and subsequent TBS-deprotection of intermediate 24 with pyridine and HF·pyridine complex [66] in a total yield of 26% over the two steps. The longest linear sequence was 7 steps, with an overall yield of 5%. Finally, the reaction mechanism of the oxidative

• , imidazole, DMF, 50 °C, 18 h; f) LAH, AlCl3, THF, rt, 12 h; g) TBHPaq, DCE, 100 °C, 18 h; h) pyridine, HF·pyridine, EtOAc, rt, 14 h. Proposed mechanism for the oxidative cyclization of amines 2a and 2b to fluorenone (3). Reactivity of different functional groups towards TBHP-mediated cyclization to give

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• compounds with heterocyclic substituents are of high biological and medicinal relevance [34][35]. Therefore, we have decided to evaluate sulfinylurea and thiourea catalysts C1 and C2 also with (E)-2-(2-nitrovinyl)furan (9) and (E)-3-(2-nitrovinyl)pyridine (11) as Michael acceptors. As Michael donor, we

• ). The aliphatic aldehydes propanal (6d) and hexanal (6b) provided medium yields and diastereoselectivity and enantioselectivity. The Michael addition of 3-phenylpropanal (6c) to (E)-3-(2-nitrovinyl)pyridine (11) required long reaction times (120 h) in solution, similar to those for the reaction with (E