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

• , herein, we utilized a copper catalyst to activate the C–I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents

• investigations demonstrated the ability of diaryliodonium salts for selective mono-arylation of 2-naphthols [34]. In this context, we embark on a strategy to modify the neighbouring position of the diaryliodonium salt with an ester group, presenting a novel copper-catalysed regioselective arylocyclization of

• diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C–I bond and esterification. The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives. The

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• compound obtained using approaches for activating silent genes, Wang et al. discovered SF2768, a metabolite produced by Streptomyces thioluteus that chelates copper as a chalkophore [63]. However, it has been suggested that activation of secondary metabolism in actinomycetes may depend on various metals

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• several positions and also form 6–14 residue cyclic peptides [37][38]. It should be noted that TycC TE was more sensitive to the amino acid changes near the site of ring closure. The alkyne-containing analogs were conjugated to a variety of azido sugars via copper(I)-catalyzed cycloaddition to obtain the

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

• would initially involve the addition of azide radicals to an alkene, generating a carbon-centered radical. Then, different trapping of this intermediate could be performed (Scheme 1B). First, C-centered radicals are known to recombine with metal-acetylides, in particular copper [27]. Reductive

• elimination of the organometallic intermediate would lead to the desired product (Scheme 1B, reaction 1). Unfortunately, this approach will not be compatible in the case of azidation since the copper, azides and alkynes present in the mixture are expected to undergo alkyne–azide cycloaddition reactions [28

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

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

• based on derivatives of imidazolidin-4-one were synthesised and characterised. The catalytic activity and enantioselectivity of their corresponding copper(II) complexes were studied in asymmetric Henry reactions. It was found that the enantioselectivity of these catalysts is overall very high and

• -(pyridin-2-yl)imidazolidin-4-one, differentiated by various substitutions at the imidazolidine ring [5][6][7]. Their copper(II) complexes were evaluated as efficient enantioselective catalysts, particularly in asymmetric Henry reactions (Scheme 1). Subsequent research has led to the development of various

• chiral metal complex catalyst but also as an enantioselective organocatalyst [17]. Accordingly, its application in enantioselective organocatalysis, particularly in asymmetric reactions through “enamine activation”, warrants further investigation. Results and Discussion The corresponding copper(II

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• aminide 7 in good yield on a gram scale (Scheme 1b). With the novel 3-aminoimidazo[5,1-b]oxazol-6-ium salt in hand, we examined its use as an NHC precursor for the preparation of late transition metal complexes. Treating compound 9a with triethylamine and either dimethyl sulfide gold(I) chloride or copper

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• ™ Impact instrument (electrospray ionization). Melting points were determined on a Fisher–Johns melting point apparatus. X-ray diffraction study The X-ray diffraction dataset of compound 3b was recorded on an Agilent SuperNova diffractometer using a microfocus X-ray radiation source with copper anode and

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

•  13) [32]. Such moiety is able to complex two copper(I) cations, both sides of the system acting as independent bipyridine units, giving the possibility of sequential opening of the tweezers one arm at a time. Indeed, when only one copper(I) cation is complexed, tweezers 22a and 22b adopt an “S

• ” intermediate conformation that is converted to a “W” conformation like the open terpyridine when complexed to a second Cu+ cation. While the “S” state is obtained with one equivalent of copper(I), the full conversion to the “W” state is more difficult to achieve and needs up to 8 equivalents. This is due to

• the reduced basicity of the second pyrimidine’s nitrogen when the first is already coordinated. The py-pym-py closed-by-default “U”-shaped systems form host–guest complexes with electron-poor guests such as TNF. These tweezers are thus a three-state system controlled by copper(I) with allosterically

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• benzophenone moiety in probe 3. The samples were then reacted with TAMRA-N3 (structure shown in Figure S4, Supporting Information File 1) under copper(I)-catalyzed azide–alkyne cycloaddition conditions [21] and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with in-gel

• are treated with a TAMRA-N3 under copper(I)-catalyzed azide–alkyne cycloaddition conditions, followed by SDS-PAGE coupled with in-gel fluorescence scanning. AMS, 5′-O-sulfamoyladenosine. Competitive labeling experiments of GrsA using probe 3 in the presence of ʟ-Phe-AMS inhibitors. (A) Labeling of

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

• substrate and participating in the key bond-forming/breaking steps via substrate–TM interactions [73][74]. This paradigm has been employed in the activation of NHPI esters under photoinduced copper (Cu) and palladium (Pd) catalysis. In 2017, Peters and Fu reported a Cu-catalyzed decarboxylative C(sp3)–N

• decarboxylative cross-coupling (DCC) of NHPI esters with organometallic reagents, resembling classic Kumada, Negishi, and Suzuki couplings, has been enabled by nickel (Ni), cobalt (Co), iron (Fe), and copper (Cu) catalysts [84][85][86][87][88][89][90][91] (Scheme 23A). The typical mechanism begins by

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

• in CH3CN) in CH2Cl2 (4a–h), CH3CN (5a–c, 6a,b, and 10c) and potentiostat–galvanostat Elins P-45X. X-ray data collection was performed on an Agilent SuperNova diffractometer using a microfocus X-ray source with copper anode (Cu Kα radiation, λ = 1.54184 Å) and Atlas S2 CCD detector. The diffraction

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

• , and this reactivity pattern was exploited as early as in the 1950s to generate in a controlled way polycyclic aromatic compounds from isolable heteropine precursors. By way of example, the phenanthrene derivative 2 was obtained by heating the dibenzo[b,f]thiepine precursor 1 in the presence of copper

• ]. Similarly to the early transformations of thiepines, sulfur elimination was triggered by copper bronze at high temperature, thus leading to the conversion of the 6-membered cyclic disulfide into the corresponding thiophene. The 1,2-dithiin scaffold is found in natural products such as thiarubrines A and B

• reactivity in the absence of external reagent (i.e., their photo- and thermal reactivity) has been far less explored than for heteropines. Nowadays, the most common protocol to trigger extrusion from 1,2-dichalcogenins and generate S- and Se-doped π-CPCs still relies on copper (as nanopowder) at high

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• -aminopyrazoles with azlactones under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium, is described by the Fisyuk group [13]. A further facile one-pot process toward a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues is described

• nucleophilic substitution of benzylic bromides with sodium azide and a subsequent copper(I)-catalyzed double click reaction in one pot [17]. In summary, these contributions by renowned experts demonstrate the broad diversity of impressive catalytic domino, tandem, and one-pot processes towards many valuable

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.20.21 Abstract An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper

• efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters. Keywords: β-carbonyl diazo; copper catalyst; fluoroalkyl diazo; Mumm rearrangement; unsymmetrical β-diacylamino

• 1 of Table 1, 54% yield product 4a was produced by this reaction in the presence of 10 mol % CuI. These results demonstrate that copper catalysis plays a crucial role in the generation of the desired product 4a. Moreover, we performed this reaction without the addition of tert-butyl nitrite (Scheme

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

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole–DBDAP hybrid. Keywords: Buchwald–Hartwig

• diverse dibenzodiazepinones via a copper-catalyzed C–N bond coupling between 2-halobenzoates and o-phenylenediamines leading to a key intermediate that undergoes an intramolecular N-acylation to afford the corresponding dibenzodiazepinone structure in high yields (Scheme 1b) [14]. Another innovative

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , China 10.3762/bjoc.20.14 Abstract An efficient and practical method for the synthesis of C5-brominated 8-aminoquinoline amides via a copper-promoted selective bromination of 8-aminoquinoline amides with alkyl bromides was developed. The reaction proceeds smoothly in dimethyl sulfoxide (DMSO) under air

• , employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields. Keywords: aminoquinolines; C–H bromination; copper catalysis; regioselectivity; Introduction

• -scale use. Therefore, novel bromination reagents and simple bromination approaches are still required to be established. Very recently, we reported a copper-catalyzed C5-bromination and difluoromethylation reaction of 8-aminoquinolines using ethyl bromodifluoroacetate as bifunctional reagent [30] and

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• wormlike nanoparticles. In rotaxanes, the utilization of metal–ligand bonding involving CuI is a common strategy for immobilizing a thread moiety within a macrocycle. However, the efficacy of such a bonding is compromised when catalysts are used in stoppering reactions, e.g., the copper-catalyzed azide

Preparing a liquid crystalline dispersion of carbon nanotubes with high aspect ratio

• Keiko Kojima,
• Nodoka Kosugi,
• Hirokuni Jintoku,
• Kazufumi Kobashi and
• Toshiya Okazaki

Beilstein J. Org. Chem. 2024, 20, 52–58, doi:10.3762/bjoc.20.7

• acetone using a bath-type sonicator and were put onto a copper grid with carbon mesh. To perform thermogravimetric analysis (TGA), a TG/DTA7300 instrument from SII Nano Technology Inc. was utilized. The DWCNT powder was preheated at 180 °C for ten minutes under vacuum and subsequently measured under

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

• Bremen, Germany 10.3762/bjoc.20.2 Abstract N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have

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

• -disubstituted-1,2,3-triazole derivatives is readily achieved via the copper(I)-catalyzed [3 + 2] cycloaddition of an azide and a terminal alkyne (CuAAC) [63][64][65]. A further alkylation of the N3 position with an alkyl halide is an equally straightforward procedure that ultimately affords a large assortment

• ). The active catalytic species for the CuAAC reaction were generated by reducing copper(II) sulfate with sodium ascorbate according to literature procedures [66][67]. 2-Azido-1,3,5-trimethylbenzene (mesityl azide) was easily synthesized in a distinct, preliminary step through the Sandmeyer reaction of

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• copper(I) iodide in DMF/DIPEA solution at 55 °C with subsequent desilylation with potassium carbonate. Finally, butadiyne 6 was prepared by a homocoupling reaction of 5 with 80% yield. Derivatives containing two dicyanopyridyl moieties, 7 and 8, were prepared starting with a Sonogashira coupling of

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

• transformations, as depicted in Scheme 14. The dual-catalytic cycle comprised a photocatalytic cycle and a copper catalytic cycle, interconnected through an intermolecular single-electron transfer. Within the context of the photocatalytic cycle, the generation of the C(sp3)-centered alkyl radical A was

• facilitated by the process of photoexcited radical decarboxylation. On the other hand, the copper catalytic cycle involved the capture of alkyl radicals by the copper complex B, the activation of heteroatom-containing substrates 30 by a base-mediated proton transfer, and the subsequent reductive elimination

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• of the final [2]rotaxanes by active template copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) as key step of the synthesis. HRMS and NMR experiments have been performed to confirm the formation of the interlocked structures. Keywords: active-metal template; clipping; copper(I)-catalyzed alkyne

• molecule which catalyzes the macrocyclization reaction around the axle (Figure 1b). Results and Discussion In order to access the target [2]rotaxanes we made use of the CuAAC reaction, performed in the presence of a copper(I) N-heterocyclic carbene, a very stable and efficient class of catalysts used in

• obtained by CuAAC in the presence of CuCl(SIMes)(4,7-diclorophenantroline) as catalyst, with very good yields. Next, we set to study the ability of compound 6 to form copper(I) complexes able to act as active-metal templates for [2]rotaxane synthesis. Therefore, complexation studies of 6 with CuCl(SIMes

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• selectivity from 6% to 97% after four hours of irradiation at 420 nm. Further efficiency enhancement was achieved by adding 1,1,1,3,3,3-hexafluoropropan-2-ol, producing CO with a TON up to 230, although at the expense of selectivity (54%). Keywords: carbon monoxide selectivity; cobalt(II) complex; copper(I

• complex obtainable via a straightforward synthesis, with improved solubility, concerning our previous Co(II) complexes [21]. Thus, the new Co(II) complex bears two 1-benzyl-4-(quinolin-2-yl)-1H-1,2,3-triazole (BzQuTr) units, that were obtained through a copper-catalyzed alkyne–azide cycloaddition (CuAAC

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• ][35][36]. Our lead compound INHHQ (or 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone) has been successfully tested in the prevention of short- and long-term memory deficits in a mice model of sporadic AD [33]. Additionally, INHHQ decreases copper-mediated production of reactive oxygen

• proved the promising anti-PD and metallophoric effect, especially towards intracellularly relevant copper(I) ions, of X1INH (1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone) [32]. This year, we evaluated the effects of the presence of three methoxy substituents in an N-acylhydrazone

• affect its pharmacological properties and metallophoric potential against copper(II) when compared to the unsubstituted counterpart. Nevertheless, the bioinspired compound was still able to reduce oxidative stress and affect the aggregation of the amyloid-β peptide, related to pathophysiological events