Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• ][23], dyes, preservatives and as ligands in complex chemistry [24][25][26][27]. In the context of our interest in the application of cross-coupling reactions to polyhalogenated heterocycles [28][29][30][31], we studied Sonogashira reactions of brominated 2-trifluoromethylquinolines. The optical

• cross-coupling reactions of various acetylenes containing electron-rich and electron-withdrawing functional groups, like methoxy or cyano, as well as thienyl and cyclopropyl groups. In general, all products were achieved in very good yields, ranging from 71 to 99%. Only product 6h, containing a TMS

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• -mentioned methods [39]. However, the longer lifetime of the triplet state usually comes at the expense of a lower energetic driving force. Helicenes in particular show an increased ISC rate compared to planar molecules, which is attributed to an enhanced spin-orbit coupling that is sensitive to their degree

• of non-planarity [40], where the helical structure allows for mixing between the singlet and triplet π,π*-states [41][42]. In addition, the insertion of heteroatoms such as nitrogen further enhances ISC due to a spin-orbit coupling between n,π*-states and π,π*-states [40], as stated by El Sayed’s

• 0.34, is essentially non-reactive under our conditions. Cyanopyridine- and sulfinate-derived radicals are produced in equal concentrations in the catalytic cycle, suggesting that radical coupling is indeed the final reaction step to give the stable sulfonylation/arylation product. The triplet of Aza-H

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• , 126, and 96 MHz) spectra were recorded in CDCl3 on a Bruker Avance III 500 MHz device. The chemical shift δ is reported in ppm, and the multiplicity of the signals is abbreviated as singlet (s), doublet (d), double of doublets (dd), triplet of doublets (td), etc. The coupling constants J are expressed

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• achieved with one-pot Suzuki–Miyaura coupling to arrange phenylene rings and pyridinylene rings in an alternating fashion. Analyses with UV–vis spectroscopy showed changes in the photophysical properties with nitrogen doping, and X-ray crystallographic analyses experimentally revealed the presence of

• biased charges on the peripheral nitrogen atoms. Keywords: cross coupling; macrocycles; nitrogen doping; UV–vis spectroscopy; X-ray charge density analysis; Introduction Graphitic carbonaceous sheets of graphene continue to attract considerable attention, which lead us to explore structural defects

• were installed in an outward-radiated manner, which expands the structural diversity to exploit the chemistry at the periphery of [n]CMP (Figure 1b). Through the use of Suzuki–Miyaura coupling for macrocyclisation, pyridinyl and phenylene rings were assembled in an alternating fashion, which afforded

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• contraction reactions, yielding a benzofluorene intermediate 4 and the dimer 5, both featuring a kinamycin skeleton (Scheme 1) [11][12]. Recent investigations unveiled the catalytic activity of the O-methyltransferase-like protein AlpH, which catalyzes a unique SAM-independent coupling of ʟ-glutamylhydrazine

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• importance in organic synthesis and is widely used in the pharmaceutical and other chemical industries. Palladium-catalyzed cross-coupling reactions are one of the compelling methods for building C–C and C–N bonds [1][2]. However, using organohalide reagents and harsh reaction conditions in this process

• to the scientific community [10][11][12]. In this process, first, the metal-catalyzed dehydrogenation of the alcohol provides a reactive substrate for coupling with nucleophiles and the active metal hydride species. Later, the borrowed hydrogen is used in the final step to reduce unsaturated

• several reviews have been reported on their applications in dehydrogenative coupling reactions [21][22][23][24]. This review focuses mainly on the BH reaction to create sustainable C–C and C–N bonds with manganese catalysts. Review C–N bond formation with alcohols and amines Amines and their derivatives

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• the linear amide 11 was performed in DCM using a 10-fold excess of trifluoroacetic acid at room temperature, providing 1,4-azaphosphinine 12 in 68% yield. Various conditions used for the coupling of nucleobase 8, such as using silylated derivatives (HMDS, BSA) or salts obtained by base treatment (NaH

• C5 and C6 atoms (Figure 1). Towards this end, we developed a synthetic strategy for these nucleosides and identified that assembly of the nucleobase on the sugar was more viable than coupling of the final nucleobase to Hoffer’s chlorosugar (13). It is interesting that only the charge-neutral

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• bonds of aryl halides also exhibit high reactivity, particularly towards transition-metal-mediated cross-coupling processes or Ar-SN reactions. Benzyl and aryl halides, collectively referred to as 'aryl-cored halides', have found extensive applications across various fields, including synthesis [1

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• synthetic strategy leading to pyridones bearing different aryl substituents is described in Scheme 2. During the Suzuki–Miyaura cross-coupling reaction, which introduced the substituents in the C-5 position, the methyl ester protection of the amino acid moiety was also cleaved, leading directly to the final

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• trifluoroacetic acid, followed by coupling with 1,3,5-trimethoxybenzene [18] (Scheme 1A). This process demonstrated tolerance for a wide range of electron-rich and electron-deficient (hetero)aryl iodine(III) compounds. Wirth and colleagues reported the flow synthesis of diaryliodonium(III) trifluoroacetates using

• increase in temperature facilitates the ligand coupling between the phenyl group and the carboxylate counterion. When heated at 140 °C for 2.5 h under solvent-free conditions, iodonium salt 7aa underwent carboxylate O-phenylation with complete phenyl group transfer, resulting in the formation of phenyl

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• relaxation rate (saturation), accompanied by linewidth broadening (saturation broadening). ACFs show moderate saturation phenomena with simple saturation broadening as the excitation power increases, where the coupling with conduction electrons in nanographene sheets is the primary path for spin energy

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• complexes are important for the synthesis of heterocyclic and non-heterocyclic compounds. In 2009, Arthuis and co-workers developed a new process for the synthesis of 2-aroylindoles and 2-heteroaroylindoles by a one-pot palladium-catalyzed domino reaction that involves an initial C,N-coupling followed by

• carbon monoxide insertion, and Suzuki–Miyaura coupling reaction, from 2-gem-dibromovinylaniline [12]. In the presence of Pd(PPh3)4 (5 mol %) as catalyst, 5 equivalents of base (K2CO3), an aryl- or heteroarylboronic ester (1.1 equivalents), CO (12 bar), in dioxane at 100 °C after 16 h the indole

• derivatives were isolated with good yields (Scheme 1). Instead, in the Senadi et al. approach, 1-(3-amino)-1H-indol-2-yl)-1-ketones were obtained through a Pd(0)-catalyzed cascade process consisting of isonitrile insertion as carbon monoxide surrogate and a C–H cross-coupling [13]. The reaction took place in

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• complexity in a synthetic route. The palladium-catalyzed coupling of arenediazonium salts with olefins, the Heck–Matsuda reaction, has been instrumental in this strategy involving the desymmetrization of cyclic systems [3], especially five-membered substrates [4][5][6][7]. As we have demonstrated previously

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• unreliable isolation of acyl fluoride intermediates, we next considered whether BT-SCF3-mediated deoxyfluorination of carboxylic acids could be coupled with a subsequent acylation in an overall one-pot process. Selecting amines as nucleophilic coupling partners, a short optimisation study was carried out to

• functionalisation chemistry such as coupling reactions (5g, 5m, 5n). Heteroaromatic (5o) and aliphatic carboxylic acids (5j, 5p, 5q) also reacted smoothly under the optimised conditions. As demonstrated by the efficient formation of amide 5q in 84% yield, the process is tolerant of significant steric bulk at the

• , replacing the benzylamine coupling partner with phenylalanine methyl ester provided dipeptide 5t in 67% yield (Scheme 3b). With the scope of the deoxyfluorination process established, our attention turned to an investigation of the reaction mechanism (Scheme 4). As demonstrated in our previous work

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

• Abstract The development of a new and straightforward chemoselective method for the synthesis of uracil-based structures by combining Suzuki–Miyaura and Sonogashira–Hagihara cross-coupling is reported. The methodology was applied to synthesize a series of novel compounds. The tolerance of the combination

• -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

• this work, we report a new chemoselective method for the synthesis of a series of hitherto unknown uracil-based compounds by combining Suzuki–Miyaura and Sonogashira–Hagihara cross-coupling [60][61]. The method is designed to be flexible and could also be used to synthesize other structural motifs

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

• group in the product can be leveraged as a versatile synthetic handle, allowing for the preparation of hitherto inaccessible types of densely functionalized N-vinylazoles. Keywords: alkynes; azoles; cross-coupling; hypervalent iodine; Introduction N-Functionalized azoles are prevalent in bioactive

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

• reaction of azoles with alkynes and iodine(III) electrophile, benziodoxole triflate (BXT, 1; Scheme 1c). Displaying exclusive trans-selectivity, the reaction tolerates a broad range of azoles, including pyrazole, 1,2,3-triazole, tetrazole, indazole, and benzotriazole, with internal alkynes as coupling

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• esterification of alcohol (±)-5 gave redox active ester (±)-6, which was itself shown to be a suitable substrate for nickel-catalysed decarboxylative cross coupling reactions to aryl-substituted BCPs (±)-7. Oxidation of alcohol (±)-8 gave acid (±)-9 which yielded amine (±)-10 after a Curtius rearrangement

• metallophotoredox coupling reactions to deliver nitrogen- and aryl-functionalised BCPs such as (±)-17 and (±)-18. In the reports of Baran, Collins and co-workers and of MacMillan and co-workers, isosteres of compounds including telmisartan (isostere = BCP 21) and lomitapide (isostere = BCP 22) were prepared and

• aryl ((±)-54a) and heteroaryl ((±)-54b) substituted 1,2-BCHs. As an alternative synthesis of 1,2-BCHs, and importantly also enantioenriched examples, Qin and co-workers developed an intramolecular coupling of cyclobutane-tethered sulfonylhydrazones and boronic esters (not shown) [41]. They also

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

• for the synthesis of functional materials via cross-coupling reactions. Next, we extended our investigation to 1-naphthol in this reaction, and found that the arylation of 1-naphthol was achieved selectively at the C-2 position. The cascade cyclization resulted in the corresponding products 3an and

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• 18 containing an exocyclic alkene was subjected to the reaction conditions, a mixture of benzylic chlorides (20) was formed in low yields, and trace amounts of the allylic chloride 19 was also isolated, the materials differentiated on the basis of the coupling of the acetal H5 with the respective

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• -sensitive substrates. Another challenge, shared with Nicewicz's method [90], is the preparation of arylacridine 159 in a single step from the relatively expensive 9-chloroacridine through Pd-catalyzed cross-coupling with 2-chlorophenylboronic acid. Additionally, for large-scale reactions, a flow reactor is

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• a similar peptide (GABA-(Lys)5-peptide-PEG) on resin for the reaction with compound 3. Initial trials, using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N-methylmorpholine (NMM), respectively, as a coupling reagent and a base, and 5 equiv of peptide on

• (32%) when HBTU was used as a coupling reagent. Finally, use of a greater excess (6.0 equiv) of peptide on resin relative to 3, and a combination of HBTU and DIPEA as the coupling reagent and base, provided the C60–peptide conjugate in an isolated yield of 41% (based on the used compound 3). The yield

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• properties and to modify the profile of biological activity due to optimum fluorine lipophylic properties, and enhanced interaction with lipid membranes [12][13][14]. Pentafluorophenyl-substituted porphyrin systems are especially useful for the connection of various functionalities capable for coupling with

• synthesis and characterization of tris(carboranyl)porphyrins of A3B-type (where “B” corresponds to the substituent responsible for bioconjugate coupling) based on the transformations of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin which was used as a basic compound for the synthesis of new boronated

• linkers capable to connect these porphyrins with biomolecules, thus improving their biomedical characteristics and theraputic efficacy for PDT and BNCT due to the combination of different substituents within porphyrin framework. Amide coupling of A3B-type carboranylporphyrin containing an amino

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

• -workers developed an elegant chemoenzymatic route in 2000 [36]. The synthesis commenced to construct linear decapeptide 2 by global SPPS method on 2-chlorotrityl resin. After coupling 2 with N-acetylcysteamine (NAC, 3), the mimic of peptide-S-PCP, peptide-SNAC 4 was prepared. When incubated with purified

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

• TE-catalyzed marcolactonization [69]. The synthesis of linear peptide 34 commenced with the lactone opening of 26 to afford Weinreb amide 27. Following primary alcohol protection and amide reduction, the aldehyde 28 was coupled with iodide 29 to afford 30 via Nozaki–Hiyama–Kishi coupling, which was

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

• with potential for further modification by cross-coupling. The full scope of the transformation can be found in Supporting Information File 1, Schemes S2 and S3 [45]. Concerning scope limitations, the azido-alkynylation of vinyl-pyridine 1b was unsuccessful and thiazole 1c only afforded 18% of the

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an