Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• reaction. In order to clarify the coordination reaction of nitrogen atoms, Bazan’s group designed a conjugated polymer containing pyridine and thiazole groups and small molecule 15 (Figure 8) and compared the 1H NMR spectra and 19F NMR spectra after the addition of 1 equivalent B(C6F5)3 at various

• temperatures from 230 to 300 K (see Figure 9) [43]. As shown in Figure 9a, when the temperature reached 280 K, the aromatic resonances became intense, implying the appearance of a new species, which was assigned to the Lewis acid–base adduct. Fifteen new resonance peaks were also observed in the 19F NMR

• small molecule 15 containing pyridine and thiazole groups reported by Bazan et al. and pyridine groups-containing diketopyrrolopyrroles (DPP) 16–18 investigated by Huang et al. (a) 1H NMR spectra in the aromatic region and (b) 19F NMR spectra of compound 15 (top) and the mixture with 1 equivalent B(C6F5

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• . A plausible reaction mechanism. Optimization of the reaction conditions.a Supporting Information Supporting Information File 48: Synthetic schemes for products, characterization data, and copies of 1H, 13C, and 19F NMR spectra. Funding We gratefully acknowledge funding from Jiangsu Provincial

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• NMR). 19F NMR spectra were recorded on a Bruker-400 spectrometer. Coupling constants (J) are given in Hz. The following abbreviations were used to designate the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet, br = broad. Melting points were measured

• copies of 1H, 13C, and 19F NMR spectra. Funding This work was supported by the American Association of Colleges of Pharmacy (2018 New Investigator Award to H. V. L.), the National Institute of General Medical Sciences (P30GM122733 pilot project award to H. V. L.), and funds from the Department of

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• monofluorinated product 2c in 51% yield. Analysis of the milled mixture by 1H and 19F NMR spectroscopy also revealed the presence of difluorinated products 2c' and 2c''. The product composition of the reaction of 1c with NFSI (1.0 equiv) remained unchanged at lower milling speeds (25 Hz vs 30 Hz), but the use of

• , we reacted a mixture of NFSI and imidazole (3a) by ball milling. Analysis by NMR spectroscopy of the crude reaction mixture showed that 1-(benzenesulfonyl)imidazole (4a) had been formed in 41% yield (Scheme 3a). Complementarily, 19F NMR spectroscopy of the crude reaction mixture evidenced a

• distinctive peak at 65.8 ppm in the 19F NMR spectrum (Scheme 3g), which was assigned to phenylsulfonyl fluoride (PhSO2F) [35], a byproduct often obtained in reactions with NFSI [36][37]. Trying to improve the rheology of the reaction mixture and to increase the basicity of the medium, we milled 3a and NFSI in

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• yield obtained for the synthesis of 3bc (R1 = 5-OMe, 75%), the aromatic aldehyde 2c substituted with a similar electron-rich group (R1 = 5-NEt2) gave only a regular 40% yield for 3bb. The structures of the new Schiff bases 3 were characterized by 1H, 13C, and 19F NMR spectroscopy and HRMS techniques

• . The structural assignments for the synthesized quinolines 1a–f were consistent with the 1H, 13C, and 19F NMR spectra described in the literature [14]. When the 1H NMR spectral data were recorded in CDCl3 as a solvent for the 3aa–be series and compared with the NMR spectral data of the 1a–f series, the

• similar structures described in the literature [7][14][22]. The CF3 group bonded at C-4 was assigned as a quartet with 1JCF ≈ 274.6 Hz, with chemical shifts of 123.52 ppm, on average. The 19F NMR spectra in CDCl3 showed a singlet at −61.70 ppm, on average, in relation to the CF3 group. Furthermore, there

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• Vertex 70 spectrometer in KBr pellets. The NMR spectra were recorded with Varian VXR-300 (400, 500, 600) instruments (300, 400, 600 MHz for 1H, 188 MHz for 19F and 100, 125, 150 MHz for 13C) in CDCl3 and DMSO-d6 solutions, with TMS as an internal standard. Multiplets were assigned as s (singlet), d

• determination, 1H/13C/19F NMR spectra for all compounds.

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• base led to the identification of Pd(PPh3)4 (10 mol %), arylboronic acid (1 equiv), K3PO4 (2 equiv) in THF/H2O 1:1 as ideal conditions providing enamides 2aa and 3aa in a 93:7 ratio in 90% 19F NMR yield (Table S1 in Supporting Information File 1). The optimized conditions were applied to the scope

• -substituted enamides. Substrate scope of the Suzuki coupling leading to enamides 2 and 3. aRatio determined by 19F NMR; byield determined by 19F NMR using PhCF3 as an internal standard; cisolated yield; disolated as a mixture of isomers E/Z = 64:36. Proposed mechanisms for the formed Suzuki coupling retention

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• were characterized by 1H NMR, 13C NMR, HRMS, and 19F NMR (5b, 5c and 5h) spectroscopy wherever applicable. The structures of compounds 3, 5c and 7b were unambiguously confirmed by single crystal X-ray analysis diffraction method. Single crystal X-ray structure analysis supported the formation of the

• protons of –N–CH2-CH2–Ph. A singlet peak at δ 1.86 is attributed to methyl protons on the imidazole ring. The 19F NMR spectrum of 1H-1,2,3-triazole compound 5c showed a singlet at δ −113.61 corresponding to one fluorine atom of the phenyl ring. The high-resolution mass spectrometric data at 317.1141 (M

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• described how attempts to synthesize 22-1 proved to be unsatisfactory [42] and in 1995, they reported their synthesis characterized only by 19F NMR and described that the salts were moisture-sensitive [84]. The synthesis is sensitive to solvents and the amount of Brønsted acids (HX). N,N’-Difluoro-1,4

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• was observed at the less sterically hindered benzylic position. The proposed reaction mechanism for radiofluorination is depicted in Figure 2. Although the trans-difluoro-substituted Mn(IV) complex is the reactive F-transfer intermediate in 19F chemistry, the formation of a trans-18F-difluoro

Correction: Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2021, 17, 1725–1726, doi:10.3762/bjoc.17.120

• graphical abstract is shown in Scheme 2. We apologize for any inconvenience caused. Corrected Scheme 4 of the original article. Scope of the Et3B and the DICAB-initiated SF5Cl additions on alkynes. Unless noted otherwise, isolated yields are reported. aYield estimated by 19F NMR analysis of the crude

• mixture using 2-fluoro-4-nitrotoluene as an internal standard. Corrected graphical abstract of the original publication. Supporting Information Supporting Information File 130: General information, synthetic procedures, additional optimization results, NMR spectra for known compounds (1H, 19F) and full

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• uracil with fluorine or trifluoromethyl improved PNA binding affinity for complementary DNA and RNA [127]. Moreover, fluorination increased the cellular uptake of PNAs [127]. Fluorinated uracil derivatives are also useful probes for studying different binding modes of PNA using 19F NMR [128]. PNA

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• device (1H: 600 MHz; 13C: 150 MHz; 19F: 565 MHz) in CDCl3. If not otherwise specified, the chemical shift (δ) is given in ppm. Materials Reactions were carried out under an argon atmosphere using predried glassware, if not noted otherwise. Benzhydrazides 1 were synthesized according to a previously

• . Proposed reaction pathway. Optimization of the copper-mediated C−H/N−H functionalization with terminal alkyne 2a.a Supporting Information Supporting Information File 232: Characterization data for 3 and copies of 1H, 13C, and 19F NMR spectra. Funding Generous support by National Natural Science

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• and benzophenone and freshly distilled before use; anhydrous DMF was purchased and used as received. The NMR spectra were measured on a Bruker AVIII instrument (1H at 600 MHz, 13C at 151 MHz, and 19F at 565 MHz). Chemical shifts are reported relative to residual undeuterated solvent peaks (for CDCl3

• : 1H NMR δ = 7.26 ppm, 13C NMR δ = 77.0 ppm; for 1,1,2,2-tetrachloroethane-d2 (C2D2Cl4): 1H NMR δ = 6.0 ppm, 13C NMR δ = 73.8 ppm) or to CFCl3 (19F NMR δ = 0.00 ppm) used as external standard. Multiplicities of the signals in 13C NMR spectra were assigned based on supplementary 2D measurements (COSY

• , 133.4 (2i-C), 134.2, 135.0 (CH each), 138.1, 139.0 (2i-C), 140.8 (q, 2JC,F = 40.8 Hz, C(3)), 174.5, 177.3 (2C=O); 19F NMR (CDCl3, 565 MHz) δ −62.82 ppm; UV–vis (CH2Cl2) λmax (log ε) 247 (4.45), 266 (4.24), 275 (4.25), 340 (3.72), 409 (2.61), 496 nm (1.70); IR (neat) νmax: 3082, 1677 (C=O), 1588, 1521

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• the 13C NMR spectrum due to the observed distorted quartet at δ 163.7 for the C=O group displaying 2JCF coupling and a quartet at δ 120.3 with a 1JCF coupling constant of 291 Hz. 19F NMR and HRMS further confirmed the presence of the recovered TFA salt of ent-pavettamine (28). However, attempts to

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• conversion and debenzylation. The values [Hz] of selected coupling constants. Boldfaced values illustrate the trends discussed in the text. Supporting Information Supporting Information File 89: Experimental procedures and spectral data. Supporting Information File 90: Copies of 1H, 13C, 19F, and 2D NMR

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• during the glycosylation with glycosyl fluorides in liquid SO2 is proved by 19F NMR spectroscopy. A sulfur dioxide-assisted glycosylation mechanism that proceeds via solvent separated ion pairs is proposed, whereas the observed α,β-selectivity is substrate-controlled and depends on the thermodynamic

• anomeric ratio observed initially for mannoside 3c (α/β = 82:18, Scheme 1). Finally, we proved the formation of the fluorosulfite species by employing 19F NMR spectroscopy (Figure 1). Glycosylation of the reaction mixture was treated with Et3N to stabilize the possibly formed fluorosulfite anions in form

• of an ammonium salt. The 19F NMR spectra of the water-soluble components was than compared to the standard obtained from the reaction between TBAF and SO2. The peak that corresponds to the FSO2− anion was observed at 38.34 ppm (TFA as an external standard, −76.55 ppm) [77]. Also DFT calculations were

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• ribonucleotide had a high resemblance to the unmodified uridine, allowing it to be used as a probe for RNA structure determination through 19F NMR [211]. This modification led to RNA which was stable and predominantly in the C3'-endo (north) conformation [211], similar to the 2',4'-diF-RNA previously reported by

• , following removal of the 3'-O-acetyl group with NH3/MeOH, some TBDMS transfer to the C3' position is seen [211]. 5'-DMT protection then led to the pre-amidite [211]. 19F NMR results show that not only does this modification allow for discernment between ssRNA and dsRNA, but it also allows for the

• nucleoside preorganization [219]. In 2011, a work detailing the first synthesis of both isomers of 3'-fluoro-modified hexitol nucleic acid (FHNA and Ara-FHNA) (Figure 1I) was published (Scheme 9 and Scheme 10) [221]. The incorporation of fluorine has long been used in siRNA [224], miRNA [225], and for 19F

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• BioSpin Ascend 400 spectrometer (162 MHz). 19F NMR spectra were recorded on a Bruker BioSpin Ascend 400 spectrometer (377 MHz). IR spectra were recorded on JASCO FT/IR-680Plus instrument. High-resolution mass spectra (HRMS) were recorded on a Bruker micrOTOF II ESI(+)/TOF instrument. General procedure for

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• containing fluorine have been particularly well characterized for their use as spectroscopic probes, mainly in 19F NMR applications [12][13][14][15]. It is typical that the incorporation of fluorine into certain molecular fragments changes the local polarity as well as the electronic and conformational

• is usually neglected for further investigations. Structural disturbances are also not welcome in spectroscopic studies of fluorine-labeled proteins by 19F NMR spectroscopy. Effectively, it is much better and easier to study a protein that is properly folded, rather than a protein that is misfolded

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• preferential formation of stable tetrahedral species I instead of the CF3 ketones 2 in the reaction mixture. However, all the yields were moderate to good. This fact could be explained by the appearance of hydrate products 4 in the 19F NMR spectrum of the crude reaction mixture [72], while the hydrates 4

• ), and e) our group in this work. Substrate scope of esters 1 for trifluoromethylation by HCF3 under the optimized conditions. aDetermined by 19F NMR of the crude 2 with trifluorotoluene as an internal standard. bIsolated yield. cIsolated yield of gram-scale reaction by using 1 g of substrate. Optimized

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• phenomenon is shown by a large downfield shift in the 19F NMR spectrum of 8 compared to the neutral precursor 7. Following these studies on the evaluation of fluorine atom(s) substitution on cation behavior, Olah et al. then investigated the expected destabilizing effect resulting from the presence of

• spectroscopic evidence for the complete ionization of several α-(trifluoromethyl) alcohol precursors 9a–c in a superacidic FSO3H–SbF5–SO2 medium. They also brought experimental 19F NMR variation values up to Δδ = +24.8 ppm (Scheme 3). This suggests a partial stabilization of the cationic center by

• partial stabilization of the cationic center by the phenyl groups. Similarly, Laali et al. observed significant 19F NMR downfield chemical shifts upon the formation of α-(trifluoromethyl)pyrenylcarbenium- and α-(trifluoromethyl)anthracenylcarbenium ions 12a–d from the corresponding carbinols 11a–d (Scheme

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• use of 19F NMR in the broad field of chemical biology [Cobb, S. L.; Murphy, C. D. J. Fluorine Chem. 2009, 130, 132–140] and present here a summary of the literature from the last decade that has the technique as the central method of analysis. The topics covered include the synthesis of new

• fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate

• biosynthesis and biodegradation of fluorinated organic compounds is also described. Keywords: biotransformation; chemical biology; fluorine; 19F NMR; probes; protein structure; Introduction Although fluorine is abundant in the environment, it is not a nutrient nor is it a feature of biochemistry for most

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• conditions.a Substrate scope for the synthesis of the α-organylthio esters 3.a Substrate scope for the synthesis of the β-organylthio ketones 4.a Supporting Information Supporting Information File 204: Experimental procedures, characterization data, control experiments, and copies of the 1H, 13C, and 19F NMR

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• )-4-methylbenzene (1a) under batch conditions. Flow cyclization of 1-(1-azidovinyl)-4-methylbenzene (1a). Supporting Information Supporting Information File 110: Description of general methods, general procedures, characterization data for all compounds and copies of 1H,13C,19F, NOESY spectra