Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• between 180 °C and 240 °C [35]. The investigation of the thermal stability of phenacyl azides 2 led to the fortuitous discovery of the competitive formation of a different heterocycle. Indeed, while phenacyl azide (2a) was stable per se in a ChCl/Gly mixture after stirring at rt for 12 h, a new

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

• units (Figure 25) [87]. Interestingly, in this approach, the purine heterocycle acted as an inherent DG for the C–H activation step. The protocol provided a broad scope of products featuring good functional group tolerance, could be performed on a gram scale and occurred under mild conditions, essential

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

• -tetrahydrocinnoline) derivatives in moderate to excellent yields. Keywords: cinnoline; 1,4-diketone; indole; indolone; N-heterocycle; Introduction Nitrogen-containing heterocycles are widespread in plenty of molecules of interest, either in materials science, optics, electronics, or biology [1][2][3][4]. They are

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• fluorescence. This may be owing to the azide moiety, either as a functional group or as part of the triazole heterocycle. Similar observations were already made for luminescent materials [74][75]. Fluorene derivatives were subjected to photophysical measurements as well. UV–vis absorption spectra of

• CuAAC. Initial photophysical investigations of azide-functionalized bromocarbaldehydes and fluorenes revealed that the azide moiety and the triazole heterocycle efficiently quench phosphorescent transitions. Efforts of installing other functional groups suitable for covalent connections or modifications

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

• aromatic heterocycle substrates within 8–20 min, transformations that would require days in batch protocols (Scheme 1) [62]. Flow systems can be pressurised easily with back pressure regulators, enhancing the solubility of gaseous reagents in the reaction solvents [36][63]. Flow processes are also commonly

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• heterocycle is present in several alkaloids such as emetine (1) and related compounds, that exhibit biological activities such as glucosidase inhibition, anti-amoebic properties as well as activity against breast cancer cell lines [2]. Notable examples of synthetic compounds include the dipeptidyl peptidase

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• that are known to have varied and robust pharmacological activity, such as isoborreverine (1) [12], mitomycin A (2) [13] and chlorizidine A (3) [14]. The indole moiety is incorporated into their structure, which is important because it is a seminal heterocycle that exhibits a wide range of biological

• nitrogen atom of the heterocycle. Since it is not clear what factors favor this relevant selectivity, the geometry and energy of the TSs were calculated for some of the diene–dienophile pairs depicted in Table 2 (vide infra). Cyclization via an intramolecular Heck arylation reaction Before attempting the

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

• transformation, the arene is first oxidized by the excited state of the photocatalyst, generating the arene radical cation I. The latter then undergoes a nucleophilic attack of the N-heterocycle, affording the radical adduct II. TEMPO and O2 act as oxidants for the formation of the final aromatic compound via

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

• of UVA-induced stress [17], and bis(2-alkylindol-3-yl) selenides III exhibit antitumor activity toward HT-1080 and MG-22A tumor cell lines [18]. The imidazo[1,2-a]pyridine ring is also an important aromatic heterocycle because its derivatives are biologically active and play an important role in

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

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• group [68] used silicon-based Grignard reagents 189 to add to conjugated heteroaromatics 188, e.g., benzoxazole (as an extension to more commonly studies ketones, esters, imines, etc.), leading to products 190–194. The heterocycle played a crucial role, as in its absence, none of the expected product

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• analogues and subject them towards biological evaluation [16][17][18][19]. In addition, our envisioned dinitrogen heterocycle cores may have increased interactions in the binding pockets, and thus leading to a better therapeutic activity. Aiming to provide a strategy to address our global objective of

• nitrogen-containing heterocycle in the core ring structure would enhance the pharmacological properties while maintaining the level of HDAC8 inhibition. The targets TOI1–4 were synthesized from commercially available starting materials in moderate yields. The synthesized compounds displayed potent activity

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• employed in diverse organic reactions, including Suzuki reactions [64], Sonogashira reactions [65], transesterifications of triglycerides [66], hydrogenation reactions [67], N-heterocycle syntheses [68], cleavage of propargyl phenol ethers [69], etc. [70][71][72][73][74][75]. In this review article, we

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• 1 with potassium selenocyanate was studied in detail. We found that the reaction of thiaselenole 1 with KSeCN at room temperature afforded a five-membered heterocycle, selenocyanate 4, in a quantitative yield. This result was unusual since previously studied substitution reactions of thiaselenole 1

• proceeded already at 0 °C, and therefore we were not able to isolate compound 5 under these conditions. The formation of the six-membered heterocycle of 2,3-dihydro-1,4-thiaselenin-2-yl selenocyanate 5 was confirmed, inter alia, by the observation of two doublets corresponding to the olefinic protons of the

• SCH=CHSe group with 3J = 9.9 Hz in the 1H NMR spectrum (Table 1, entry 2). In the case of five-membered compounds 1 and 4, the coupling constant of the olefinic protons of the SCH=CHSe group would be 3JH,H = 6.3 Hz [32][40]. The SCHSe group of the heterocycle 5 was characterized by a doublet of

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• Anna R. Bockman Jeffrey M. Pruet Department of Chemistry, Valparaiso University, 1710 Chapel Dr, Valparaiso, IN 46383, USA 10.3762/bjoc.16.46 Abstract The synthetic utility of pterins is often hampered by the notorious insolubility of this heterocycle, slowing the development of medicinally

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• proceeded well with heterocycle-containing chlorides such as 2-chloro-5-(chloromethyl)thiophene (4e), leading to 2-aminoethyl acetate product 3k in 66% yield which has potential as bifunctional monomer for polymerization. Furthermore, oxazole derivative 2,4,4-trimethyl-4,5-dihydrooxazole (2b) was also

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• large panel of carbazoles. The selectivity of the reaction using an unsymmetrical triarylamine depended on the electronic density of the aromatic ring, furnishing, in some cases constitutional isomers. Importantly, in the case of heteroaryl-substituted triarylamines, the heterocycle was incorporated in

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• basicity in one ligand. The body discusses the synthetic protocols which focus on P–C, P–N-bond formation, substrate and nucleophile types and different N-heterocycle construction strategies. Selected references are given in relation to the applications of the ligands. Keywords: ligand synthesis; P,N

• dibromomethane [2]. Substrate postfunctionalization and heterocycle construction Some heterocyclic precursors can be readily obtained via accessible synthetic protocols. The nitrogen-containing compounds can be constructed and grafted on the phosphine precursor. Some available phosphines and organic precursors

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• heterocycle. This intermediate was then trifluoromethylselenylated by [(bpy)CuSeCF3]2. While benzofurans and benzothiophenes were prepared in moderate to good yields, only marginal yields were obtained with indole derivatives (up to 25%). Finally, the reactions could easily be scaled up to a gram scale. The

• copper catalysis (Scheme 15, conditions I) [39]. Mechanistically, the authors proposed the formation of a silver(I)–SeCF3 adduct, followed by a transmetallation step, yielding the active CuSeCF3 species. Good to very good yields were obtained on a broad scope, including amide-, ester-, and heterocycle

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines. Keywords: 5-amino-1H-pyrazole-4-carbonitrile; 3-amino-1,2,4-triazole; 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines; heterocycle; multicomponent reaction; ultrasonication; Introduction Tetrahydropyrimidines are heterocycles of high pharmacological

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• cyclopentenone ring [37], as this heterocycle is a powerful synthon for the synthesis of a variety of bioactive target molecules, due to the broad diversity of chemical modifications available for the enone structural motif [38]. The most common approach to access such chemotype is the Pauson–Khand (PK) reaction

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• heterocycle. Keywords: amides; isoxazole; isoxazoline; liquid crystal; thiourea; Introduction Thioureas are a structurally diversified group of organic compounds, with technological applications in different areas. The structural diversity of the thiourea moiety is linked to possibly one or both nitrogen

• components, which may be substituted symmetrically or unsymmetrically [1]. Applications of this scaffold include complexing agents in anion sensors [2] organocatalysts [3], intermediates in heterocycle synthesis [1] and development of compounds with pharmacological effects [4]. Considering the importance of

• mesophase. A monotropic smectic C mesophase (SmC) at 198 °C was observed for amide 19. Perfluorinated thioureas 17b and 18b presented an SmA mesophase, independent of the nature of the 5-membered heterocycle. The perfluorinated alkyl chain in both compounds is the reason of preference for a lamellar SmA

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• energy associated to the formation of a seven-membered heterocycle would favour the competitive ring closure leading to the five-membered ring (Scheme 2, reaction a), which would involve attack of the carboxamide nitrogen to the ω-carbon. On the other hand, the higher nucleophilicity of the sulfur in the

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

• well as on the electronic substitution pattern of the alkynone. While electron-donating groups furnish α-pyrones as main products, electron-withdrawing groups predominantly give the corresponding 1H-pyridines. Both heterocycle classes fluoresce in solution and in the solid state. In particular

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• heterocycle formation [11]. Presumably, a prototropic shift in the enamine-imine intermediate 4 is followed by electrocyclization to the cyclic azomethine ylide, which then reacts with dimethyl fumarate in a 1,3-dipolar cycloaddition. The suggested mechanism accounts for the trans-position of the methyne