One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• schistosomiasis [22][23][24][25]. The combination of the privileged heterocycles tetrazole and tetrahydroisoquinoline in one molecule generates new molecules which could have biological activities. A standard Ugi four-component reaction (Ugi-4CR) of an aldehyde, amine, isocyanide, and a carboxylic acid produces

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• -coupling; fluorescence; heterocycles; regioselectivity; Introduction Organic life is a complex interplay of many different building blocks. One of these building blocks is uracil. Discovered for the first time in 1901 by Alberto Ascoli, it is now known to be one of the four nucleobases of RNA [1]. It

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• natural products and pharmaceutical agents, including antifungal drugs [1][2][3], and hence their selective preparation has attracted considerable attention from the synthetic community. Compared to methods for the de novo construction of azole heterocycles, direct functionalization of the azole N–H bond

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• acid, trifluoroborate moiety, trifluoromethanesulfonate, aryl sulfonamides, and heterocycles, have been incorporated into the ortho-position of diaryliodonium structures [16][17][18][19][20][21]. Ortho-trimethylsilyl or boronic acid-substituted diaryliodonium salts can serve as aryne precursors. Ortho

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• desired product, which proved to be unstable during purification (Scheme 4). Homopropargylic azides containing electron-rich nitrogen heterocycles could not be obtained. No product was observed by using vinylindole 1d probably due its high tendency to polymerize. Although a slight amount of

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• IV structure arose from the ligand IIIb structure – the imidazolidin-4-one ring present at ligand IIIb was formally replaced by a pyrrolidine one. Here, we presume the comparable coordinating ability of both species of heterocycles. However, the pyrrolidine cycle of ligand IV does not contain alkyl

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• ) or a bromine atom. These transformations yield spiro-annulated O-heterocycles with succinimide ring, namely spiro-Δα,β-butenolides 2 and 3, tetrahydrofurans 4 and benzopyrans 5 (Scheme 1). Fragments of these oxygen-containing spiro-conjugated heterocycles are part of many important drugs and natural

• multitarget drugs against COVID-19 [36], and amiaspochalasin C isolated from the solid culture of Aspergillus micronesiensis [37] and 1,9-epoxy-9a-hydroxystenine from the roots of Stemona tuberosa [38]) (Figure 1). Hence, the development of novel synthetic methods to construct spiro O-heterocycles constitutes

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

• tetrachlorophthalimide (TCPhth) active esters towards C(sp3)–N cross-couplings with nitrogen heterocycles (Scheme 27). The catalytic reaction was proposed to begin by oxidative addition of RAE 104 to catalyst Bi-1, forming an in cage radical pair consisting of BiII species 130 and α-amino radical 107 (Scheme 27B

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• widened the scope and provided an access to derivatives of N,O- and N,S-heteropentacyclic quinoxalinophenoxazine, triphenodioxazine and oxazinophenothiazine systems. Keywords: 3H-phenoxazin-3-one; fluorescence; molecular structure; pentacyclic heterocycles; synthesis; Introduction 3H-Phenoxazin-3-one

• probes, organic light-emitting diodes, and organic solar cells [2][7][8][9]. The principal way for the preparation of these heterocycles involves the coupling of 3H-phenoxazin-3-ones with variously functionalized aromatic amines. This is followed by the cyclization of the initially formed adducts [10][11

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• stimuli. In the next section, chalcogen extrusion resulting from the contraction of 6-membered rings upon photo- and thermal activation will be detailed. Contraction of 6-membered rings coupled to chalcogen extrusion Ring contraction of 6-membered heterocycles containing chalcogen atoms has been employed

• between carboranes and chalcogen-doped π-conjugated heterocycles, Yang and co-workers devised a two-step strategy for the synthesis of carborane-fused thiophene 43 (Scheme 11, bottom) [72]. Double lithiation of carboranyl indole 41 was followed by trapping with disulfur dichloride as chalcogen source to

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• ][20][21][22][23][24][25][26][27], which can be readily generated in situ from α-halogeno hydrazones, have been extensively applied in recent years as versatile building blocks in inverse-electron-demand Diels–Alder (IEDDA) reactions [28][29][30] to construct diverse nitrogen-containing heterocycles

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• reaction with neutral or anionic bases. Keywords: dipyrido[3,2-e:2′,3′-h]acenaphthene (acenaphthylene); hydrogen bonding; π-stacking; substitution reactions; tele-elimination; Introduction Quinoline derivatives, classical nitrogen-containing heterocycles, are widely distributed in nature in various forms

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

• relevant heterocycles in high efficiency [10]. The Chan–Lam coupling is considered a greener alternative to traditional C–N coupling reactions, as it can be carried out under mild reaction conditions (room temperature and short reaction times, etc.), plus it does not require expensive metals like Pd, being

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• enables a rapid access to heterocycles containing a trifluoromethyl group. Keywords: cascade reaction; indole derivatives; photocatalysis; radical chain process; trifluoromethylation; Introduction Dihydropyrido[1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• ; heterocycles; photocyclization; photosensitizer; styrylpyridines; Introduction DNA intercalators – most often represented by small planar heteroaromatic compounds – play an important role as chemotherapeutic agents [1][2][3][4]. Specifically, upon intercalation into the DNA double helix such ligands can cause

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• a subsequent Glaser–Hay coupling reaction, a RA acceptor unit was introduced to provide a DTF-IF-RA donor–acceptor scaffold with a low-energy charge-transfer absorption and multi-redox behavior. Keywords: alkynes; chromophores; fused-ring systems; heterocycles; redox chemistry; Introduction

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• properties of the triazoles thus obtained [9][10][11][12]. It should be noted that the synthesis of amidines containing other heterocycles in addition to 1,2,3-triazole in the molecule has not been described in the literature. In this regard, it is of interest to develop an effective method for the synthesis

• of hybrids of 1,2,3-triazole with other heterocycles and to identify biologically active compounds among the synthesized compounds. It is known that the cycloaddition reaction of azidopyrimidinediones with enamines [13] represents an effective method for the synthesis of pyrimidinyl amidines [14

• ] (Scheme 1A). A few years ago, we discovered that the replacement of enamines with 2-cyano-N,N-dialkylethanethioamides in this reaction [15] led to the formation of amidines containing two heterocycles: pyrimidine-2,4-dione and 1,2,3-thiadiazole (Scheme 1B). The idea came to our mind to construct a system

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense

• followed by a ring-closure starting from 2,2'-diiodo-1,1'-biphenyls [15][16][17]. Related one-pot procedures are also described (Scheme 1b) [18][19]. Such 2,2´-dihalobiphenyls are established starting materials for synthesizing a variety of heterocycles. Usually, their utilization leads to the production

• diaryliodonium salts [29][31], as well as Pd-catalysed methods for synthesizing N-aryl carbazoles [32]. Similar procedures were published for the Cu-catalysed synthesis of aryl carbazoles from amines as well as other heterocycles such as N-acyl acridanes with nitriles using cyclic iodonium salts by Wen and Chen

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• heterocycles; zwitterions; Introduction Following the seminal discovery from the group of Arduengo, who isolated and fully characterized 1,3-di(1-adamantyl)imidazol-2-ylidene in 1991 [1], stable divalent carbon species have evolved from fleeting intermediates to ubiquitous catalysts, ligands, and reagents in

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• component into a glutarimide framework employing a Rh2(esp)2-catalyzed N–H insertion with the involvement of N-Boc-α-diazo glutarimide. The new diazo reagent is more stable, soluble and convenient to prepare than the previously suggested one. The approach permits the application of diverse heterocycles

• , including both aromatic and saturated NH-substrates. This yields structures that are appealing for generating cereblon ubiquitin-ligase ligands and for potential use in crafting PROTAC molecules. Keywords: CRBN ligands; diazocarbonyl compounds; N–H insertion reaction; N-heterocycles; Rh(II)-catalysis

• molecules and CRBN ligands are being published (over 400K patents in the last 5 years according to SciFinder). Various nitrogen heterocycles were utilized as a heterocyclic moiety linked to a glutarimide core via a nitrogen atom. In addition to the phthalimide fragment, the most commonly studied ones are

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the ability to be readily transformed into various valuable functional molecules, including amines, hydrazines, and nitrogen-containing heterocycles [13]. In a significant advancement in 2021, Lopchuk et al. revealed a novel method for the photodecarboxylative alkylation of diazirines 12 using the

• ). Impressively, this transformation exhibited exceptional versatility, extending beyond coumarins to encompass other nitrogen-containing heterocycles, including quinoxalinones, with remarkable C-3 regioselectivity. The findings of this study significantly expanded the synthetic toolbox for accessing

• functionalized coumarin derivatives and related nitrogen-containing heterocycles, opening up exciting possibilities for their diverse applications in other fields. Similarly, the regioselective photodecarboxylative C–H alkylation of 2H-indazoles and azauracils using NaI/PPh3 as mediators and redox esters 3 was

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• [44] (Scheme 6). El Kaim and Jia reported a Mannich-type reaction of trifluoroacetaldehyde hydrazones with formaldehyde and aromatic aldehydes to obtain valuable starting materials for the generation of other trifluoromethyl-substituted heterocycles. The study demonstrated that the electron

• blocks for the synthesis of heterocycles [46][47]. The resultant heterocycles bearing a fluorine or fluorine-containing group have been used in a broad array of pharmaceutical applications [48][49]. The use of di/trifluoromethylated hydrazonoyl halides as building blocks for the synthesis of di

• reactions and indicate their potential offering an efficient approach to fluoroalkylated heterocycles in drug design. Trifluoromethylated acylhydrazonoes Acylhydrazones are a well-established class of organic compounds with the –CONH–N=CH– structure, and some variants show potential pesticidal and

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• -type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products. Keywords: [3 + 2] cycloaddition; decarboxylation; 1,3-dipolar; double cycloaddition; one-pot synthesis; multicomponent reaction; semi

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• the Lewis acid to realize the sp3 C–H-bond activation of nitrogen heterocycles to synthesize isoxazole derivatives. Results and Discussion At the outset of this study, we chose the reaction of 2-methylquinoline (2a) with phenylacetylene (1a) in the presence of AlCl3 (3 equiv) and sodium nitrite (10

• 11). With the optimal reaction conditions in hand, various alkynes were examined as dipolarophiles (Scheme 2). A range of functional groups were tolerated in this reaction, such as alkyl, methoxy, halo, and heterocycles. It was found that electron-deficient groups in the phenyl ring (3g–i) were more

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• compounds are the more active ones. Keywords: antioxidant; deep eutectic solvent; Knoevenagel; ʟ-proline DES; rhodanine; Introduction Rhodanines and related five-membered heterocycles with multiple heteroatoms (i.e., thiazolidinediones, thiazolidinones, hydantoins, thiohydantoins) are very interesting

• and DPPH radical at 517 nm. Ascorbic acid (AA) was used as a reference compound. Examples of rhodanines and related five-membered heterocycles with interesting biological activities. Synthesis of 5-benzylidenerhodanine derivatives. Conditions: areaction performed for 3 h at 60 °C. bReaction performed