Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• , which provided the products in high yields with up to 33% ee [19]. In 2023, García Mancheño and co-workers reported the tetrakis(iodotriazole) 3-catalyzed dearomatization of halogen-substituted pyridines 4, which formed the corresponding products 5 in high yields with up to 90% ee (Figure 1b) [20

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• formation releasing Cu(OTf)2. The final bicyclic product 33 arises from isomerization and water elimination. Recently, Singh's research group developed a cascade process to access imidazo[1,2-a]pyridines-linked isoxazoles 35. Isoxazole carbaldehydes treated with 2-aminopyridines and isonitriles in the

• -dihydroquinazolin-4(1H)-one derivatives 26. Synthesis of polysubstituted pyrroles 27. Enantioselective synthesis of polysubstituted pyrrolidines 30 directed by the copper complex 29. Synthesis of 4,5-dihydropyrazoles 31. Synthesis of 2 arylisoindolinones 32. Synthesis of imidazo[1,2-a]pyridines 33. Synthesis of

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• Suzuki couplings and the reduction of the thiazole moiety to 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a crucial intermediate, using BH3⋅NH3 and tris(pentafluorophenyl)borane as a Lewis acid, followed by treatment with formic acid. Gillie et al. reported the synthesis of a laterally fused N-heterocyclic

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• compounds such as phenols, coumarins, pyridines, pyrimidines, quinolines, and others. This has resulted in the production of numerous valuable products. The reaction's appeal lies in its simplicity and the fact that there is no requirement to protect sensitive functional groups, thus making the introduction

• determined that room temperature is inadequate for fully oxidizing substrates. The optimal oxidation temperature for uracils 1 and 4 is between 60–65 °C, whereas for pyridines 7 and 9 it is 45 °C. Heating the reaction mixture at a temperature higher than the optimum level causes the substrates to be

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• three different reactions (Figure 11A). Mechanistic model transferability for CPA-catalysed Minisci reactions [125] was utilised for the derivatization of quinolines and pyridines. Models trained on these compound classes show good generalisation towards other nitrogen-containing heteroaromatics

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• , Scheme 10. In line with all prior MCRs, good yields were observed with no deuterium scrambling. Calcium channel blockers derived from this methodology are heavily metabolized by CYP3A4 via dehydrogenation to afford inactive pyridines, Scheme 11 [54]. As such, bio-isosteric deuterium–hydrogen exchange at

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• one, which is consistent with the finding of ketone side-product. In 2018, the group of Zhang established an intramolecular C(sp2)–H functionalization of aldehyde-derived N-(2-pyridinyl)hydrazones 15 to produce 1,2,4-triazolo[4,3-a]pyridines 16 (Scheme 4) [39]. Interestingly, the hydrazone was in situ

• applications in industry. Synthesis of triazolopyridinium salts [34][35][36]. Synthesis of pyrazoles [37]. Synthesis of indazoles from ketone-derived hydrazones [38]. Intramolecular C(sp2)–H functionalization of aldehyde-derived N-(2-pyridinyl)hydrazones for the synthesis of 1,2,4-triazolo[4,3-a]pyridines [39

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• , this approach was applied to the synthesis of N-substituted pyrazoles and poly-substituted isothiazoles [24][25]. Glycine derivatives can be reacted with indoles using copper catalysis or metallophotoredox catalysis [26]. Le et al. reported the use of the same approach for imidazo[1,2-a]pyridines [27

• underrepresented in the peer-reviewed literature in comparison to phenyl groups or their six-membered counterparts (e.g., pyridines, pyrimidines) [42]. Furthermore, the increasing importance of small heteroaromatic rings containing nitrogen, sulfur and/or oxygen in medicinal chemistry is well depicted by the list

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• specific heteroaromatic subsection indicates no biologically relevant data has been reported up to date. Review 2‑Heteroarylethylamine scaffolds of biological importance Six-membered heteroaromatic rings Pyridines: IL4I1, interleukin-4 induced gene 1, encodes ʟ-phenylalanine oxidase IL4I1 present in the

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• achieved during the last five years, and classifies them into five categories: synthetic methods, building blocks, scaffolds, biological activities and physical properties. Keywords: Groebke–Blackburn–Bienaymé reaction; multicomponent reactions; heterocycles; imidazo[1,2-a]pyridines; isocyanides

• also in the work reported by Shankar et al. [10], already mentioned in chapter 1. The authors established a solvent-catalyzed GBB-3CR to synthesize glycosylated imidazo[1,2-a]pyridines 33 starting from 1-formyl glycals 32; using HFIP as the solvent, the addition of any metal catalyst was not needed

• acetonitrile (not shown) led to the formation of benzoxazolpyrroles 106 (X = O) and indolizines (not shown), respectively. The GBB reaction is a powerful tool for the construction of imidazo[1,2,a]pyridines. Khan et al. [69] envisioned an isocyanide-free protocol based on arylglyoxals 107, 2-aminopyridines and

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• tolylhydrazonoyl chloride derivative 54 [35]. The reaction conducted in the presence of silver acetate at room temperature, achieved yields of 78–81% of the 16-spiropyrazolines 55a,b (Scheme 17). 6-Spiroimidazoline steroids In 2015, Dar’s group reported a small library of spiroimidazo[1,2-a]pyridines obtained

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• higher yields of 84% and 71%, respectively. The steric inhibition of a doubly substituted phenyl ring was observed in a diminished formation of 2,6-dichlorobenzaldehyde (4m) in 39% yield. Naphthalen-2-ylmethanol gave aldehyde 4n in 44% yield. Pyridines 4o and 4p were also compatible and gave good yields

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• reaction is a three-component condensation of an α-amino heterocycle (e.g., 2-aminopyridine) 1, an aldehyde 2, and an isonitrile 3 providing the corresponding fused imidazoles (e.g., imidazo[1,2-a]pyridines) of general formula 4 (Scheme 1) [18][19][20][21]. Imidazo[1,2-a]pyridines and related heterocycles

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of

• pharmaceuticals, and the reductive syntheses of these heterocycles from pyridines and quinolines have been well studied [12]. Although these transformations have been studied intensively, such reductive reactions usually require harsh reaction conditions such as high reaction temperatures and high pressure of

• , and pyridines using PEM reactors [51][52]. In this context, we have focused on the synthesis of nitrogen-containing molecules using a PEM reactor. Herein, we report the application of a PEM reactor for the reduction of cyanoarenes, nitroarenes, quinolines, and pyridines. These reductions proceeded

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• Vladislav V. Nikol'skiy Mikhail E. Minyaev Maxim A. Bastrakov Alexey M. Starosotnikov N.D. Zelinsky Institute of Organic Chemistry RAS, Leninsky prosp. 47, 119991 Moscow, Russia 10.3762/bjoc.20.94 Abstract An efficient method for the synthesis of isoxazolo[4,5-b]pyridines has been developed on

• ]triazol-4-yl)pyridines was observed. Keywords: aromatic nitro compounds; Boulton–Katritzky rearrangement; isoxazolo[4,5-b]pyridines; nucleophilic substitution; 1,2,3-triazoles; Introduction Nitrogen heterocycles represent a very important class of organic compounds that has found application in various

• fields of chemistry and materials science. These compounds are widespread in medicinal chemistry [1][2][3], production of high-energy-density compounds [4][5][6][7], and many others. In particular, isoxazolo[4,5-b]pyridines are of considerable interest due to their remarkable variety of biological

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• ], pyrazolo-fused benzophenazines [45], 4,5-dioxopyrrolidines [46], 1,2-dihydropyridine (1,2-DHPs) [47], pyrimido[4,5-b]quinoline-tetraones [48], tetrahydrobenzo[b]pyrans and indazolo[2,1-b]phthalazinetriones [49]. Herein, we report the synthesis of imidazo[1,2-a]pyridines via the GBB-3CR using HPW as

• % yield (compared to the expected 91% yield) was obtained (Scheme 1b). This reaction was carried out in triplicate with the same outcome. Therefore, the search for a broader and more reliable methodology to obtain imidazo[1,2-a]pyridines using heteropolyacids became necessary. Due to its already mentioned

• obtained. Meta,para-substituted aromatic aldehydes showed a high reactivity with yields greater than 84% for products 4s–w. Notably, the use of tri-substituted aromatic aldehydes gave imidazo[1,2-a]pyridines 4x–z in moderate to excellent yields (35–99%), though the hydroxy substituent at the ortho position

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• show good acyl-ACP thioesterase inhibition in line with strong herbicidal activity against commercially important weeds in broadacre crops, e.g., wheat and corn. The desired substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines were prepared via an optimized BH3-mediated reduction involving tris

• introducing a nonaromatic motif via preparation of the novel 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 7. Results and Discussion Although the 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine scaffold looks relatively simple at a first glance, it displays a very different reactivity compared to the parent naphthyridine

• series. Likewise, 1,8-naphthyridines are easily accessed in high yield and on a multigram scale via Friedländer synthesis [18]. This was in clear contrast to the intermediate thiazolo[4,5-b]pyridines and the desired 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine that we wanted to access, with approaches to

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• , the terpyridine adopts an open "W"-shaped conformation due to the s-trans-conformation between two pyridines forced by the repulsion of the nitrogen lone pairs. Upon metal coordination the pyridine units rotate to allow for a tridentate binding to the metal cation, thus inducing a molecular motion to

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• -chain alkyl ethers in the presence of DBU under relatively mild conditions (Scheme 29b) [92]. In 2018, Wang et al. developed the cobalt-catalyzed oxidative CDC reaction of 2-arylimidazo[1,2-a]pyridines with isochroman using molecular oxygen as an oxidant (Scheme 30) [93]. These reactions involved a

• chemoselective and regioselective CDC between pyridines and ethers, which used Sc(OTf)3 as the catalyst and DTBP as the oxidant (Scheme 36) [101]. This strategy allowed the synthesis of a series of α-substituted pyridine derivatives. The control experiments showed that the mechanism may proceed via a radical

• operation, wide substrate range, and atom economy. It provides a new strategy for constructing functionalized pyridines. The reaction undergoes the following four processes: initially, DTBP is decomposed into two tert-butylperoxyl radicals A under heat. Then, the tert-butylperoxyl radical converts the ether

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• Elena Y. Mendogralo Maxim G. Uchuskin Perm State University, Bukireva st. 15, Perm, 614990, Russian Federation 10.3762/bjoc.19.74 Abstract A semi-one-pot method for the synthesis of 4-substituted tetrahydrofuro[3,2-c]pyridines by the Pictet–Spengler reaction was developed. The method is based on

• the condensation of easily accessibly 2-(5-methylfuran-2-yl)ethanamine with commercially available aromatic aldehydes followed by acid-catalyzed Pictet–Spengler cyclization. Using this approach, we synthesized a range of 4-substituted tetrahydrofuro[3,2-c]pyridines in reasonable yields. The reactivity

• of some of the products was investigated and selected synthetic transformations of the obtained tetrahydrofuro[3,2-c]pyridines were shown. Keywords: acid hydrolysis; 1,4-diketone; tetrahydrofuro[3,2-c]pyridines; Paal–Knorr reaction; Pictet–Spengler reaction; Introduction Hydrogenated furo[3,2-c

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• , incorporating different units that allow the integration within the corresponding materials. Thus, the incorporation of coordinating groups (i.e., pyridines or carboxylates) in the molecular design will allow the integration of such rotaxanes in MOFs [70], while other substituents will be necessary to prepare

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C–H functionalization and

• methodologies are being developed for the synthesis of functionalized pyridines or its integration into an organic molecule [12][13][14][15][16][17][18][19][20]. Although classical organic synthesis is incredibly effective, it frequently requires the prefunctionalization of substrates and involves

• , diversely functionalized pyridines have been synthesized via C–H activation under transition-metal and rare earth metal catalysis, including C–H alkylation, alkenylation, arylation, heteroarylation, borylation, etc. Recently, metal-free approaches have also been developed for the C–H functionalization of N

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• investigation revealed a sequential sp2 and sp3 C–H activation, followed by functionalization driven by zinc acetate coupled with the photocatalyst PTH. A variety of imidazo[1,2-a]pyridines and related heterocycles were explored as substrates along with several active methylene reagents, all generating the

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• moieties in several bioactive pharmaceuticals and natural products [1][2][3][4]. Moreover, due to their susceptibility towards 'exited-state intramolecular proton transfer' phenomena, IPs are also effective in optoelectronics and materials sciences [5][6]. C-3-functionalized imidazo[1,2-a]pyridines are

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• trifluoromethylthiolation of azacalix[1]arene[3]pyridines by C–H bond activation using a complex of Cu(ClO4)2·6H2O and the shelf-stable Me4NSCF3 [115][116] as a nucleophilic source of SCF3 (Scheme 3) [100]. Within these conditions, a set of six azacalix[1]arene[3]pyridines bearing electron-donating groups, halogens or

• % yields, respectively. This reaction proved to be compatible with the presence of an ester (8c) or a halogen (8e). Other directing groups, such as substituted pyridines (9a and 9b) and pyrimidine (9c) turned out to be also efficient in this transformation (Scheme 5, 4 examples, up to 84% yield). The same

• ) were found to be suitable substrates leading to the corresponding products 12h and 12i in 91% and 83% yields, respectively. The use of other directing groups was also suitable for this transformation such as methyl and cyano-substituted pyridines 13a,b, pyrimidine (13c), pyrazole (13d), as well as the