Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• in many natural products, pharmaceuticals, and bioactive molecules. For instance, some pyridine derivatives have been used for therapy of HIV, cancer, inflammation, microbial infection and so on [1][2][3][4][5]. In addition, it is also an important synthetic unit, which is frequently used as catalyst

• or ligand in organic chemistry [6][7][8][9][10]. Therefore, the development of efficient methods for the synthesis of pyridine derivatives has attracted considerable attention [11][12][13][14]. The industrial synthetic methods of pyridines mainly involve: i) extraction from coal tar; ii) condensation

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• by direct fluorination (10% F2/N2) of the pyridine in acetonitrile and in the presence of a suitable salt at low temperature (method B in Scheme 10). This one-step process was successfully applied to many other pyridine derivatives (method B in Figure 2). It was finally shown that the stable N

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• B undergoes cyclocondensation to yield the spiro product 139, whereas for 139a intermediate B falls prey to intramolecular cyclo condensation (Scheme 54). The synthesis of regioselectively functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 142 was demonstrated by Jiang and co

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• trifluoromethylthiolated product at all, despite complete saponification of the methyl ester. Conclusion In conclusion, we demonstrated the decarboxylative trifluoromethylthiolation of lithium 2- and 4-pyridylacetates to synthesize pyridine derivatives with a trifluoromethylthio group at a tertiary carbon center adjacent

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

• transformed to the corresponding N-sulfonyl amidines by reactions in 1-propanol via two- or one-pot procedures. Pyridine-2,6-dithioamide was shown to react with mesyl and arylsulfonyl azides to form pyridine derivatives bearing two N-sulfonyl amidine moieties in excellent yield. Depending on the structure of

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

• acetal (2a) and 1,3-dicarbonyl compounds was developed by using AlCl3 as a catalyst. The developed chemistry is also successful for the synthesis of functionalized pyrazolo[3,4-b]pyridine derivatives. This study offered a complementary method to construct pyrrole scaffolds through [1 + 2 + 2] annulation

• . Direct synthesis of pyrrole-3-carboxamide derivatives. Plausible mechanism of the three-component reaction. Synthesis of polysubstituted pyrazolo[3,4-b]pyridine derivatives. Optimization of the conditions for the reaction between 1a, 2a, and 3a.a Supporting Information Supporting Information File 500

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

• 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

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• form 2,5-bis(2-phenylethynyl)pyridine (3m) under identical conditions (Table 3, entries 12 and 13). By comparison with the conversion of 4-chloro-1-iodobenzene (1g), no formation of 1,4-bis(phenylethynyl)benzene was detected. It agrees with the activated substituents of 2-substituted pyridine

• derivatives. It can be concluded that by varying electronic and steric properties of substituents of the iodoaromatic substrates at all ortho-, meta-, and para- positions, no significant changes in the product yields were achieved according to previous studies [26][41]. Regarding the negligible influence of

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• -dimethylaminophenyl substituent furnishes α-pyrone 6g (Table 4, entry 13). For synthesizing 1H-pyridine derivatives 8 with an electron-donating group we employed the isolated dimer 7 and were able to isolate 1H-pyridines 8 in 52 and 34% yield (Scheme 10). Crystal structure of 1H-pyridine 5a The structure of 1H

• Supporting Information File 1) [50][51][52][53][54][55][56][57]. Photophysical properties Photophysical properties of 1H-pyridines 5 and 8 1H-Pyridine derivatives 5 are yellow or orange compounds under daylight (Figure 3, top) and fluoresce in solution (Figure 3, center) and in the solid state (Figure 3

• ) Å, C11–H···N2 127°. Symmetry transformations are i = 1−x, 1−y, 1−z; ii = x, 3/2−y, −1/2+z, iii = 1−x, −1/2+y, −1/2−z. 1H-Pyridine derivatives 5 as solids under daylight (top), under UV light (λexc = 365 nm, c(5) = 10−4 M) in dichloromethane solution (center), and under UV light (λexc = 365 nm) in

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• (III) with terarylene III showing the photomodulation of emission intensity [23]. A number of diarylethene ligands with a perfluorocyclopentene bridge were designed. Yu and co-workers reported a series of 2-(thiazol-2-yl)pyridine derivatives [24][25][26]. Reversible photoinduced release and trapping of

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• (Scheme 79). Also, phenyl, thiophene, and pyridine derivatives achieved regioselectively trifluoromethylation with N-pivalamide as a directing group. The authors also proposed a possible radical pathway for this reaction. The final trifluoromethylated compounds were generated from pivalamido arenes and

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• of biologically active imidazo[1,2-a] pyridine derivatives [108]. Encouraged by the direct synthetic strategies for imidazo[1,2-a]pyridines (IPs), Donthiri et al. have reported an efficient Cu-catalyzed C–H functionalization of pyridines with vinyl azide derivatives [109]. Their use of vinyl azide

• , perhaps because the α,β-unsaturated double bond affected the iodination. Mohan et al. successfully developed an efficient copper-catalyzed aerobic oxidative amination of C(sp3)–H bonds to synthesize imidazo[1,5-a]pyridine derivatives [122]. The reaction was also applicable to amino acid derivatives, as

• single-electron transfer (SET) with CuI followed by hydride abstraction/intramolecular nucleophilic addition and loss of a proton forming the desired compound 49 (Scheme 19). Cu(I)-catalyzed intramolecular oxidative C–H amidation of N-pyridylenaminones 61 for the synthesis of imidazo[1,2-a]pyridine

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• aminoazole fragments. In all earlier described experiments with participation of different α-aminoazoles as binucleophiles the reaction cascade readily accomplished by the formation of fused heterocyclic systems [25]. An analogous three-component reaction involving indole or imidazo[1,2-a]pyridine

• derivatives instead of 2-aminoimidazoles is referred in the literature as Yonemitsu reaction or Yonemitsu-like reaction [26][27][28][29][30][31]. The similar Michael-type adducts 6 were isolated [31] from the reaction of imidazo[1,2-a]pyridine with aldehydes and Meldrum’s acid in acetonitrile in the presence

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• with trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a tertiary amine as base a broad range of pyridine derivatives was accessible (Scheme 3). According to its discoverer, we named this reaction Flögel pyridine synthesis [21]. The reaction is very flexible with respect to the employed

• alkoxyallenes, nitriles and carboxylic acids and due to the two differently protected oxygen functions of the pyridin-4-ols these intermediates could be further substituted, e.g., through palladium-catalyzed reactions, to give highly substituted pyridine derivatives in a great variety. The scope and limitations

• are excellent precursors for the synthesis of specifically substituted heterocycles (Scheme 30). The intramolecular aldol-type condensations leading to a manifold of pyridine derivatives PY was already subject of a review article [23]. In this report, we demonstrate that the β-ketoenamides KE are also

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• obtained as a mixture of mono- and bis(pyridine) adducts. In terms of initiation efficiency, the pyridine-derivatives turned out to be more efficient than the corresponding phosphine-containing complexes. In the copolymerization of NBE (46) and COE (47), complexes 49–52 afforded the corresponding

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• . Carbocyclic or heterocyclic fused pyridine derivatives are an important class of compounds omnipresent in natural products and biologically relevant synthetic compounds [23][24][25][26][27]. For example, imiquimod is an immune response modifier used to treat warts on the skin and certain type of skin cancer

• received less attention. For instance, the multicomponent reactions of aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitriles and 5-aminopyrazol or naphthylamine afforded indole substituted fused pyridine derivatives [56]. 2-Indole substituted pyridine derivatives have also been prepared through AlCl3-induced C

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -hydroxyaryl)pyridine derivatives bearing a carboxylate or a nitrile group suitably placed at C3 position of the aza-ring has been achieved in acceptable chemical yields with a broad functional group tolerance. This sequential C–C/C–N bond making process proceeds through a regioselective allylic alkylation/aza

• products [4], medicines [5], chelating agents in transition metal complexes [6][7], and material science [8][9]. Pyridine derivatives such as vitamins B6, B3 (niacin), and nicotinamide adenine dinucleotide (NAD) play a significant role in the metabolism process of living organisms. Consequently, many

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• pyridine derivatives was possible on treatment with KOt-Bu at −23 °C, presumably with formation of potassium triflinate [27]. In our case, pyridine was used as solvent and the reaction mixture was heated up to 70 °C. This could allow pyridine itself taking the double role of nucleophile and base, leading

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• synthesis of polyarylated systems. All obtained ortho-methoxy-substituted derivatives of pyridine 2 and 6–9 as well as ortho-chloro-substituted pyridine derivatives 13, 15–17 are chiral molecules and therefore a method for enantiomer discrimination was needed, especially in the case of the planned

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• ’-O-acetylthiomethyl-containing RNA, produces various 2’-O-alkyldithiomethyl (RSSM)-modified RNAs bearing lipophilic or polar groups through a thiol disulfide exchange reaction with alkyldisulfanyl-pyridine derivatives (Scheme 3). In a preliminary evaluation, the RSSM modifications were shown to

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• not only be attributed to the fairish PLQY and the efficient RISC process from T1 to S1 of CN-P1 emitter, but also owed to the reasonable high T1, good charge mobility, and well-matched PL spectrum of the mCP host with the CN-P1 absorption spectrum. Still based on pyridine derivatives, Pan et al

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• pyrazolo[3,4-b]pyridine nucleus 37 (Scheme 6). Aziz et al. [51] developed an acid-catalyzed synthesis of pyrazolo[3,4-b]pyridine derivatives 40 through the reaction of enaminone 38 with 5-aminopyrazole (R = Ph, 16) in acetic acid (Scheme 7). The proposed reaction mechanism involves the generation of new

• enaminone intermediate 39 which underwent condensation and cyclization within C-4 of 5-aminopyrazole and the carbonyl group of the enaminone to generate pyrazolo[3,4-b]pyridine derivatives 40. However, the formation of pyrazolo[1,5-a]pyrimidine 41, a structural isomer of 40 was obtained when 1-NH-5

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R