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

• been given much attention in various research fields, such as the discovery of lead compounds in medicinal chemistry, or combinatorial chemistry [95][96]. Copper-catalyzed synthetic protocols Ghosh and Mishra [97] have successfully reported the synthesis of imidazo[1,2-a]pyridines in a three-component

• -benzenedicarboxylate), Puthiaraj and co-workers have unprecedently discovered the catalytic activity of this metal-organic framework (MOF) for the synthesis of imidazo[1,2-a]pyridines [100]. The three-component, one-pot reaction between 1, 3 and nitromethane (10, Scheme 5) involved an intermolecular aza-Michael

• heterogeneously catalyzed synthesis of imidazo[1,2-a]pyridines from 3 and ketones 20 has been reported (Scheme 7) [101]. Titania-supported CuCl2 (CuCl2/nano TiO2) played the role of catalyst in this transformation under aerobic conditions. Titania support helped in recyclability of the copper salt to four

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• ]triazolo[4,3-a]pyridines was accessed through a 5-exo-dig-type cyclization of chloroethynylphosphonates and commercially available N-unsubstituted 2-hydrazinylpyridines. In addition, 3-methylphosphonylated [1,2,4]triazolo[4,3-a]quinolines and 1-methylphosphonylated [1,2,4]triazolo[3,4-a]isoquinolines were

• synthesized in a similar manner. The presence of a NO2 group in the starting hydrazinylpyridine induces a Dimroth-type rearrangement leading to 2-methylphosphonylated [1,2,4]triazolo[1,5-a]pyridines. Keywords: cyclization; fused-ring systems; nitrogen heterocycles; phosphorylation; rearrangement

• imidazo[1,2-a]pyridines [4]. In continuation of this study, herein we report an effective approach to the synthesis of new phosphonylated triazolopyridine derivatives by reacting chloroethynylphosphonates with 2-hydrazinylpyridines. The triazolopyridine ring is a structural fragment that is present in a

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• )-2-oxobut-3-enoic acid (5b) [52][53] with 5-amino-3-methyl-N-phenylpyrazole (6) (HOAc, Δ, 5 h). As a result, two different types of pyrazolo[3,4-b]pyridines containing the carboxylic group either at C4 position (compounds 4a,b) or at the C6 position (compound 7b) were synthetized (Scheme 2). We

• easier work-up stage as well as due to avoiding the formation of impurities of the dihydropyrazolo[3,4-b]pyridines. Thus, starting from the same set of reactants two different types of heterocyclic acids 4 and 7 containing two diversity points were obtained. Afterwards compounds 4a,b were introduced into

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , Boruah’s group has been very active in the synthesis of nitrogen heterocycles such as pyrimidines, pyrazolopyrimidines and disubstituted pyridines fused to rings A and D of steroids [47][48][49]. Thus far, most applications of MCRs in steroid derivatization aimed at producing derivatives for screening

Design of a double-decker coordination cage revisited to make new cages and exemplify ligand isomerism

• Sagarika Samantray,
• Sreenivasulu Bandi and
• Dillip K. Chand

Beilstein J. Org. Chem. 2019, 15, 1129–1140, doi:10.3762/bjoc.15.109

• spectrum of compound 1a showed single set of peaks (Figure 2(ii)) characterized by complexation-induced downfield shifts of protons belonging to the terminal pyridines (Δδ = 0.77, 0.52, and 0.29 ppm for Ha, Hb, and Hc, respectively) as compared to the free ligand L1. The peak positions of Hf and Hg

• S27–S31). The 1H NMR spectrum of compound 3a showed a single set of peaks (Figure 3) featured with complexation-induced downfield shifts of protons belonging to the terminal pyridines (Δδ = 0.79, and 0.47 ppm for Ha, and Hb, respectively) as compared to the free ligand L1. The peak position of Hf did

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

• ). Condensation of 1,2-diketones DK with o-phenylenediamine to quinoxalines QU1–7 (CAN = cerium ammonium nitrate). The LANCA three-component reaction leading to β-ketoenamides KE and the structure of functionalized pyridines PY, pyrimidines PM, pyrimidine N-oxides PO, oxazoles OX, 1,2-diketones DK and

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• -catalyzed intramolecular annulation of alkyne-tethered hydroxamic esters for the synthesis of isoquinolones and pyridines without using external oxidants (Scheme 1a) [22]. Recently, we reported an intramolecular annulation of benzamides to synthesize indolizinones through RhIII-catalyzed C(sp2)–H activation

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• approaches towards this tempting scaffold are reported in the literature. They can be divided into two groups: oxidation of pyrrolo[3,2-c]pyridines [13][15][16] and annulation of pyridine by a pyrrole-2,3-dione moiety (cyclization of 2-(4-((alkoxycarbonyl)amino)pyridin-3-yl)-2-oxoacetates [11], interaction

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• -triflate pyrazinium salts to also generate γ-lactones [12]. Grignard reagents have been used as nucleophiles on a variety of N-acyl-activated pyridines in the production of natural products and biologically active small molecules [13][14][15][16][17][18][19][20]. To our surprise, there are no reports on

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• annulation patterns. Biologically relevant imidazo[1,2-a]pyridines and chromenes. General view of the molecule 7b in the crystal state (CCDC 1849215). Anisotropic displacement parameters are drawn at 50% probability. Domino formation of imidazopyridines and current work. Scope of the reaction between N

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

• ]pyridine has been reported as inhibitors of cytochrome P450 [33]. Furthermore, muscopyridine is being used in perfume industry [34]. Among the several methods available for the synthesis of pyridines or cycloalkyl-fused pyridines [23][24][25][26][27][35][36][37][38][39][40][41][42][43][44], the one-pot

• compounds. The indole–cycloalkyl[b]pyridine-3-carbonitriles comprising ortho/ortho-para/ortho-meta substituted phenyl rings exhibited axial chirality due to restricted C–C single bond rotation. Examples of biologically important cycloalkyl-fused pyridines. Axial chirality due to restricted C–C bond rotation

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

• ketimines; one-pot sequential; pyridines; Introduction Substituted pyridines are one of the most fascinating classes of heterocyclic molecules which are present in many biologically active natural and synthetic products [1][2][3]. In addition, several pyridine scaffolds have been used in agro-chemical

• contributions have been made by synthetic chemists to search for new method for the efficient synthesis and functionalization of pyridines. Among the most significant techniques are condensation reactions between reactive carbonyls and amines (namely Hantzsch [10] and Chichibabin pyridine synthesis [11][12

• construction of pyridines bearing a carboxylate or CN group at C3 position has been a lucrative target for chemists due to the pharmaceutically privileged status (Figure 1). In this context, Rodriguez’s group successfully established a one-pot three-component reaction between β,γ-unsaturated α-ketoesters, 1,3

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

• the importance of the factors governing the selectivity in the Suzuki–Miyaura reactions and encouraged us to study the factors that are important for the mechanism of the formation of selected 3,4,5-triarylated pyridines. Results and Discussion In the last few years we have been interested in the

• ). Considering further applications of atropisomeric arylated pyridines in the design of new materials like molecular switches [4], it would be desirable to estimate their thermal stability. We therefore performed kinetic experiments in order to establish the value of the barrier to rotation in the

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• exhibits three sets of peaks at 8.20 (d, 8H), 7.71 (t, 4H) and 7.20 (t, 8H) ppm for the o-, p-, and m-ring protons, respectively, of the equivalent pyridines and the methyl protons of the acetate ligands appear as a sharp singlet at 2.06 (s, 12 H) ppm (see Supporting Information File 1, Figure S1). In the

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• aldehydes worked well including para-nitro (7), ortho-methyl (8), and para-methoxy groups (9). Other notable examples include heterocycles, such as basic pyridines, thiophenes, and furans 16–18. Additionally, aliphatic 13 and 20 and alkenyl aldehydes 21 performed well providing synthetically useful

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• -valent cobalt system for C–H functionalization [16][36]. Thus, the reaction of 2-aryl pyridines 3 with internal alkynes in the presence of 10 mol % CoBr2, 20 mol % PMePh2, and 1 equiv of MeMgCl as a reductant yielded ortho alkenated products 4 with high regio- and stereoselectivities (Scheme 5) [36]. The

• strategies, remote C4-selective alkylation of pyridines [74] was also feasible with alkenes as Kanai et al. reported (Scheme 24a) [75]. The addition of pyridine (34) to alkenes in the presence of 1 mol % CoBr2, 20 mol % BEt3, and LiBEt3H as a hydride source provided branched-selective products 35a with

• /Matsunaga and co-workers reported a hydroarylation reaction of activated alkenes with phenyl pyridines 3 in the presence of the air-stable [Co(III)Cp*(benzene)](PF6)2 catalyst, giving hydroarylation products 37 in good yields (Scheme 25) [37]. The reaction proceeds through directed ortho C–H metallation to

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• pyridines, cf. 7e, is also very encouraging, as these find widespread use in pharmaceuticals as benzene isosteres, which are more polar and metabolically stable, but lack the – often problematic – basicity of regular pyridines. Compounds such as 7c are not commonly encountered, but definitely have the

• the formation of aromatic thioethers by functionalising C–H bonds of imidazo[1,2-α]pyridines and benzo[d]imidazo[1,2-b]thiophenes using Eosin B and sulfinic acids (Scheme 8) [51]. The manipulated heterocycles, particularly the imidazopyridines, are motifs which are commonly encountered in medicinal

• compatibility. Hajra et al. have reported the direct C–H thiocyanation of substituted imidazo[1,2-a]pyridines, using ammonium thiocyanate, in combination with Eosin Y under irradiation by blue LEDs (Scheme 9) [52]. This is another photoredox example of C–S bond formation, in this case to a highly versatile

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• [3,4-b]pyridines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidinones [12][13][14][15][16][17][18]. The majority of methods used in the generation of the pyrazolo[1,5-a]pyrimidinones employ a two-step process, which first requires the synthesis and isolation of the intermediate 5-aminopyrazoles

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• feature (hetero)aryl aromatic groups such as 9-deazapurines, pyrimidines, pyridines and phenyl groups connected by a C–C bond to a sugar (or sugar mimic) as shown in Figure 4 [30][45][46][47][50][54][55][56][57]. The change in the nature of the glycosidic bond is accompanied by i) increased hydrolytic

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• the synthesis of other organic scaffolds such as furans and pyridines, via cycloaddition/retro-cycloaddition tandem processes (Figure 1d) [10][11][12][13]. A classical example is the preparation of pyridoxine (a form of vitamin B6) using this approach [14][15]. There are several methods for the

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

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

• extensively employed as useful synthons in designing and constructing a plethora of fused pyrazoloazines of potential synthetic and medicinal interest viz pyrazolo[3,4-b]pyridines 7 [18], pyrazolo[1,5-a]pyrimidines 8 [19], pyrazolo[3,4-d]pyrimidines 9 [20][21], pyrazolo[3,4-b]pyrazines 10 [22], pyrazolo[5,1-c

• practical guidance to synthetic chemists for further research. Synthesis of pyrazolo[3,4-b]pyridines Pyrazolo[3,4-b]pyridines are important fused heterocycles due to their well-known synthetic and medicinal potential as good vasodilators [29], hypotensive [30], HIV reverse transcriptase inhibitors [31

• ]pyridines and their applications brings great interest in this area. The most commonly applied method for the preparation of pyrazolo[3,4-b]pyridines uses 5-aminopyrazole as synthetic precursor [36][37][38][39]. Regardless to substantial studies in this field, researchers are still focused to provide

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• construction of the quindoline system. Synthesis of condensed pyridines mediated by a σH-adduct. Formation of condensed isoxazole derivatives. Reaction of unprotected indole ester 1c with 4-chloronitrobenzene. A plausible mechanism for the formation of 11-(phenylsulfonyl)indolo[3,2-b]quinolines. The synthesis

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• good tolerance to many functional groups, such as unsaturated double bonds, triple bonds and even unprotected OH group. Different heteroaromatic amines were also amenable to this conversion, including pyridines and pyrazoles. A mechanistic study indicated that an aryl radical and CuCF3 were involved in

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• furans or pyridines. Thioamide derivatives Formation of benzothiazoles Already in 2012, Li et al. envisioned a photoredox protocol for the synthesis of 2-substituted benzothiazoles applying [Ru(bpy)3](PF6)2 as photocatalyst and molecular oxygen as oxidant (Scheme 31) [66]. As starting material