Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• 19F NMR spectroscopy to monitor the consumption of the gem-difluoro starting material 1, which was completely consumed within 16 h (Figure 3). However, a 48 h time course gave a superior yield (Table 1, entry 13 vs entry 20). We hypothesize this might be due to the volatile nature of the gem

• . Additionally, 30% of the aniline byproduct was also isolated, which explains the modest yields of this reaction and the sluggish nature. To investigate the mechanism of the current transformation, we conducted a series of experiments including a time course of the reaction using 19F NMR spectroscopy (Figure 3

• and beyond. The Z-geometry of INT-1 was determined from its 3JH−F coupling constant of 35.7 Hz in the 1H NMR with a matching J value in the 19F NMR. This is in agreement with Cao’s report on the geometry of N-(α-fluorovinyl)azoles [33]. The configurations of the E- and Z-isomers were determined by

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• of enones 2a,e,n with an excess (5 equiv) of AlBr3 or AlCl3 in CH2Cl2 solution at room temperature for 3 days afforded complex mixtures of compounds. Then, the protonation of compounds 1 and 2 in TfOH was investigated by means of NMR spectroscopy. According to the 1H, 13C, and 19F NMR data, hydroxy

• -protonated forms B is substantially delocalized from the carbonyl group to vinyl carbon C3. For fluorophenyl-substituted compounds and cations 1d and Ad, 2d and Bd, also a large downfield shift of the corresponding fluorine signals is observed in the 19F NMR spectra (∆δ = 25.3–25.7 ppm), which shows a

• ketones 1a,c,f,i into the corresponding enones 2 and indanones 3 in TfOH at 80 °C for shorter reaction time under the conditions of incomplete conversion of the starting compounds.a 1H, 13C, and 19F NMR data of compounds 1, and 2 in CDCl3 and their O-protonated forms A, and B, respectively, in TfOH

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• NEt3·3HF, AgHF2 could also be used. The complexes were found to be air-stable in the solid state and moderately stable in solution. They were unambiguously characterized on the basis of NMR studies including 19F NMR and X-ray crystal analysis. With the IMes ligand, an air-stable bis(NHC)Cu(I) complex

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• . To close the cycle and reform the oxo ligand on the Mn(V) species, a stoichiometric amount of iodosylbenzene is used in the reaction. While initial development of this reaction focused on incorporating the stable 19F, subsequent study expanded the scope to RLT of the unstable 18F radioisotope, an

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• found to shift to lower ppm values because the Hα nuclei have been affected by higher electron density caused by the formation of the halogen-bonded complex between 2a and DABCO. To confirm that the shift of Hα was indeed produced by a halogen-bonding interaction, 19F NMR analysis of compound 2d, which

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• stereochemistry of the main isomer, the 19F,1H-HOESY NMR spectrum of compound 6c was recorded. The spectrum shows direct correlation of one fluorine nucleus of the difluoromethyl phosphonate group with two cyclopropane protons at 1.75 and 2.91 ppm, respectively. Thus, it is conceivable that the major

• Pr2 and Pr4 (ΔG = −42.5 and −43.3 kcal·mol−1; cis-6c), respectively. This is consistent with the experimental results, since two sets of signals corresponding to the diastereoisomers trans-6c and cis-6c are always observed in the 19F NMR spectrum of the crude mixture, with a slight preference for the

• slight preference for one diastereoisomer. The presented results turn of a new page for the future of diazo chemistry. 19F,1H-HOESY spectrum of compound 6c. Previous works (A–D) and the extension (this work). Synthesis of diethyl 2-diazo-1,1,3,3,3-pentafluoropropylphosphonate (5). Scope of the

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• , obtaining white powders with a yield of 99% in each case. The resulting sodium salts of phosphonic acids 9 and 11 were subjected to 1H, 13C, 19F, and 31P NMR spectroscopic analysis as well as mass spectrometry (MS) confirming their purity. The spectroscopic data of 9 and 11 are in agreement with the

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• 19b–d in good yields (54–69%). We were pleased to see that the CF3-substituted aza-Nazarov product 19e was isolated as single diastereomer in 76% yield along with only 8% of the minor diastereomer. Surprisingly, aza-Nazarov products 19f with a 4-Cl substituent on the phenyl ring as well as 19g and 19h

• -Nazarov cyclization. X-ray crystal structure of compound 19l. Examples of aza-Nazarov reactions. Aza-Nazarov cyclization on gram scale. Scope of the aza-Nazarov cyclization with acyclic imines. aThe syntheses of aza-Nazarov products 19b, 19c, and 19f were described previously [35]. bThe reaction was

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• experiments with the aim of identifying further applications of 2 will be reported in due course. Experimental General information 1H NMR, 19F NMR and 13C NMR spectra were recorded on JEOL ECZ 400S spectrometers. Chemical shifts of 1H NMR are reported in ppm from tetramethylsilane (TMS) as an internal

• standard. Chemical shifts of 13C NMR are reported in ppm from the center line of a triplet at 77.16 ppm for deuteriochloroform. Chemical shifts of 19F NMR are reported in ppm from CFCl3 as an internal standard. All data are reported as follows: chemical shifts, relative integration value, multiplicity (s

• ), 153.9; 19F NMR (376 MHz, CDCl3) δ −80.5 (s, 1F), −80.6 (s, 1F); EIMS m/z: 250, 252 [M]+; HREIMS: [M]+ calcd for C8H5BrClFO, 249.9196, 251.9176; found, 249.9202, 251.9172. (3-Chloro-4-fluoro-4-phenoxybut-3-en-1-yn-1-yl)trimethylsilane (7): To a solution of 2a (0.5 mmol), bis(triphenylphosphine)palladium

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• enabled straightforward reaction monitoring via 19F NMR. To this end, a 1 T benchtop NMR equipped with a flow cell was connected to the reactor outlet and used to acquire a series of spectra. In particular, a series of 128 repetitions with a 90° pulse width and a relatively long repetition time of 5.2 s

• outlet. First, we verified that the NMR yield calculated directly from the benchtop 19F NMR spectrum was in good agreement with the high-field NMR yields calculated with an internal standard (see Supporting Information File 1, Table S1). Then, a program was developed to monitor the reaction yield over

• time by automatically acquiring, processing and integrating the 19F NMR spectrum of the reaction mixture flowing in the spectrometer (see relevant code in Supporting Information File 3). In particular, the python packages flowchem [35] and nmrglue [36] were used to control the spectrometer and process

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