Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• ). Structural determination of compound 3а was performed by IR and 1Н, 13С, and 19F NMR spectroscopy as well as by LCMS and HRMS analysis. Performing the reaction with substrate 1а under the optimum conditions (see Table 1, entry 18), we examined a variety of (het)aryl- and alkenylboronic acids 2b–w as coupling

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• determined by 19F NMR spectroscopy. The values in parentheses are the isolated yield of 3. aAtropisomers of 3fA and 5fA were detected. b3.0 equiv of 2 were used. cThe reaction was carried out using 3.0 equiv of 2 in the presence of 20 mol % each of Co(acac)2·2H2O and dppp at 110 °C in a sealed tube

• . Synthesis of the fluoroalkylated indenone 6 and the indanone 7 from the indenol 3aA. The yields were determined by 19F NMR spectroscopy. The values in parentheses are the isolated yields. Stereochemical assignment of 5aA and 7 based on NMR techniques. The cross-peaks were observed through HMBC measurements

• . Proposed reaction mechanism. Screening for the reaction conditions of the cobalt-catalyzed [2 + 3] cycloaddition using the fluoroalkylated alkyne 1a and 2-formylphenylboronic acid (2A). Supporting Information Supporting Information File 454: Experimental procedures, characterization data (1H, 13C, 19F NMR

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• , decreases the environmental impact, and has new modes of action. In analytical chemistry, fluorine nuclei (19F) are ideal for quantitative integration in NMR spectroscopy, comparable to 1H NMR spectroscopy [25][26]. In contrast to 13C signals, fluorine signals are well-resolved, and the nuclear spin of

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• fluorinated isobutanol, cyclopropylmethanol and 3-oxetanylmethanol derivatives are given in Figure 5. They were measured by a 19F NMR-based method developed by our group [22][27], which is suitable for measuring the octanol/water partition coefficients P of (fluorinated) non-UV active substrates. As expected

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• °C, 19F NMR monitoring of the reaction’s progress indicated the appearance of a second product beside the 1,4-cyclohexadien-1-iminium salt 4-Ch. Further investigations revealed that the new product was the dihydrofluorene 7, resulting from 4-Ch by an intramolecular electrophilic aromatic substitution

• reaction of propyn-1-iminium salt 1a with styrene in acetonitrile was considered first and was monitored by 19F NMR spectroscopy. Whereas no reaction appeared to occur at room temperature, a slow transformation into two fluorine-containing products was observed at 70 °C, which after neutralization and work

• interest to know whether it would react with propyn-1-iminium salts 1 as a styrene or a 1,3-diene. With 3-(4-bromophenyl)propyn-1-iminium salt 1c in acetonitrile, no reaction was observed at 20 °C, but within two hours at 45 °C, an unclean reaction took place, which became evident by a multitude of 19F NMR

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• of 0 °C instead of 20 °C, for 30 min, complete conversion was achieved and the three products E,Z-9 and 10 were present in a 62:8:26 ratio as determined by 19F NMR, the remaining 4% being attributed to acetylated analogues of 9 (Table 3, entry 1). After purification, two products were obtained as a

• heterocyclic ether 10, the addition of TBAB as a bromide source was explored. To our delight, after 30 min at 0 °C, the crude 19F NMR showed that only 4% of 10 and 96% of 9 as an 84:16 E/Z mixture had formed (Table 3, entry 2). Separation of the two E/Z isomers proved challenging by column chromatography and a

• ) and CSA (2 equiv) an 84% conversion into mainly brominated lactone 15 (79%) with traces of hydroxylated lactone 14, and of bromoalkene Z-13 was determined by crude 19F NMR. The remaining 8% appeared to be the β-chloromethyllactone 19 (see Scheme 7 below), an analogue of 15 as determined by NMR

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• [49][50]. The presence of a fluorine-rich group in the structure is also beneficial for the NMR studies based on the detection of the 19F nucleus [51][52][53]. Limited attention has been given to the polarity effects in the proline analogues though. Few studies reported peptides containing proline

• analogues in complex biological systems such as peptides and proteins, especially in 19F NMR labelling, where fluorinated prolines can serve as spectroscopic probes. Potential areas for the application of fluorinated prolines are numerous, and include the design of molecular recognition systems [101

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• compounds [8][9]. The former takes advantage of the superb properties of the 18F-radioisotope as positron emitter (t1/2 = 109 min, 97% β+ emission), while the latter benefits from the excellent performance of the 19F isotope in NMR (100% natural abundance, high sensitivity, lack of endogenous background

• -aldol reaction affording the final product (Scheme 34). This mechanism was experimentally supported by the beneficial effect of water and the observation of HF-loss by 19F NMR. The catalytic version of this process was also studied. The best results in terms of efficiency and stereoselectivity were

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• organocatalyst, Selectfluor® was employed as the terminal oxidant, and an amine/HF complex enlisted as the fluoride source (please see Supporting Information File 1 for full details). The reaction was performed in CHCl3 at ambient temperature and the crude reaction mixtures were analysed by 19F NMR spectroscopy

• , carbonyl and alkynyl group are optimally preorganised with a C5 linker. With this in mind, the amide derivatives 12 and 13 were exposed to the standard reaction conditions. Curiously, the reactions were extremely ineffective yielding the respective α-fluoroketones in only 15% yield as determined by 19F NMR

• spectroscopical yields determined by 19F NMR analysis of the crude reaction mixtures using ethyl fluoroacetate as an internal standard. (A) Hammett plot varying the para-substitution on the alkyne (ρ ≈ 0). (B) Hammett plot varying the para-substitution on the catalyst (ρ < 0). An overview of the I(I)/I(III

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• : Experimental procedures, product characterization data (mp, NMR, IR, HRMS, [α]D, HPLC), and spectra (1H, 13C, and 19F NMR, HPLC). Supporting Information File 336: Crystallographic details for 12. Acknowledgements We thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. Funding We thank

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• analyzed by 19F NMR spectroscopy. A series of typical photocatalysts (for example, iridium catalysts) were ineffective in promoting the reaction. Rewardingly, a gold catalyst, [AuCl(μ-dppm)]2 [25][26][27], provided reasonable yields of 3a after one day of irradiation along with a full conversion of the

• . Yield determined by 19F NMR spectroscopy using an internal standard. Proposed mechanism of the fluoroalkylation reaction. Supporting Information Supporting Information File 332: Full experimental details, compound characterization, and copies of NMR spectra.

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

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

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• fluorescence data for 4-fluoroisoxazoles 3b and 3c, and non-fluorinated compound 2ca. Optical properties of BKIs and F-BKIs. Supporting Information Supporting Information File 68: General procedures and analytical data, including copies of 1H NMR, 13C NMR and 19F NMR spectra. Acknowledgements We wish to

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• trifluoromethoxylation methodologies. Effect of KH2PO4 – other substrates. a Conditions as for entry 15 (Table 2), 1 h residence time; b conditions as for entry 14 (Table 2), 18 h reaction time; c 0.5 equiv KH2PO4, CH3CN/CH2Cl2 1:1; d 2 equiv KH2PO4. 19F NMR yields are reported. A) Properties and B) synthesis of CF3O

• -bearing arenes; C) trifluoromethoxylation using the “second” Ngai reagent. Optimization of residence time. 19F NMR yields are reported. Scope of photoredox trifluoromethoxylation in continuous-flow. In case of different products, the major isomer is shown. The position of the CF3O group in the minor

• isomer is marked with a star. 19F NMR yields are reported. a CH3CN/CH2Cl2 3:2, 0.08 M; b CH3CN/CH2Cl2 1:1, 0.05 M; c CH3CN/CH2Cl2 5:3, 0.05 M; d CH3CN/CH2Cl2 3:2, 0.02 M; e CH3CN/CH2Cl2 5:4, 0.057 M. Reaction optimization under flow conditions. Influence of bases on the photoredox trifluoromethoxylation

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• . Interestingly, stirring 1a in DMSO solution in the presence of 30 mol % of PdCl2 at 140 °C for 17 h produced two products (56% yield for the more polar product and 37% yield for the less polar product) after purification with column chromatography. Spectroscopic analyses (i.e., 1H, 19F, and 13C nuclear magnetic

• procedures for the synthesis and characterization of fluorinated benzils 2a and 2b, fluorinated bisbenzils 3a and 3b, and nonfluorinated bisbenzil 3c. 1H, 13C, and 19F NMR spectra of 2a, 2b, and 3a–c. Cartesian coordinates of the optimized geometries of 1a, 1c, 2a, and 3a obtained from DFT calculations

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• isomers, the transoid (in which the two cyclopalladated oxazolones are in an anti arrangement) and the cisoid (syn arrangement). The presence of the two isomers in 3 is clear from the observation of two sets of signals due to the CF3CO2– ligand in the 19F NMR spectra. The major isomer shows one singlet

• stereoisomer, despite the presence of two isomers in the starting materials 3. The 1H NMR and 13C NMR spectra clearly showed the chemical equivalence of the two ortho-palladated fragments, while 19F NMR spectra showed the equivalence of the bridging trifluoroacetate ligands. This means that only the transoid

• universal attenuated total reflectance (UATR) accessory made of thallium bromide-iodide crystals (KRS-5). The 1H, 13C{1H} and 19F NMR spectra were recorded on Bruker Avance-300 and -400 spectrometers (δ in ppm; J in Hz). All spectra were recorded at room temperature in solution, using CDCl3 as deuterated

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• substrates. Based on 19F NMR studies, the authors suggested the following mechanism: first the in situ generation of a CuCF2H complex from TMSCF2H in equilibrium with the corresponding cuprate (Cu(CF2H)2−) occurred followed by the reaction with terminal alkynes under basic conditions. The resulting

• either from the pre-isolated (K(DMF))Cu(Ot-Bu)2 or in situ from CuCl, t-BuOK in DMF in a nearly quantitative yield. The copper reagent was used for the pentafluoroethylation of a panel of (hetero)aryl iodides and bromides (up to 99% 19F NMR yield) and its synthetic utility was further demonstrated with

• , pyrimidine and quinolone derivatives, for instance, when the PhenCuCF2CF3 complex was used as the pentafluoroethyl source (24 examples, up to 99% 19F NMR yield and up to 93% isolated yield, Scheme 15). Note that a complete mechanistic study was recently reported to explain the reactivity of this well

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• , triptycene-H), 7.03 (d, 4H, pyrrole-H), 6.62 ppm (s, 4H, pyrrole-H); 13C NMR (151 MHz, CDCl3) δ 146.4, 144.7, 143.5, 135.0, 134.3, 132.3, 131.6, 130.9, 126.3, 126.2, 125.6, 122.5, 119.0, 92.3, 86.4, 29.8; 11B NMR (128 MHz, CDCl3) δ 0.32 (t, J = 28.7 Hz); 19F NMR (377 MHz, CDCl3) δ −145.04 (dd, J = 57.5, 28.7

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• worse results in each case. We assume it is associated with a much greater reactivity of this reagent in relation to PyFluor. The mechanism of the PyFluor-mediated deoxyfluorination of the α-hydroxy-β-aminophosphonates 5 was previously proposed. Based on spectroscopic studies (19F,1H-HOESY, 1H,1H-NOESY

• with potential biological activity. Experimental General methods 1H NMR, 13C NMR, 19F NMR and 31P NMR spectra were obtained on a Bruker ASCEND 400 (400 MHz) and a Bruker ASCEND 600 (600 MHz) spectrometer. All 2D spectra were recorded on a Bruker ASCEND 600 (600 MHz) spectrometer. 1H NMR chemical shifts

• were expressed in parts per million downfield from tetramethylsilane (TMS) as an internal standard (δ = 0) in CDCl3 or CD3CN. 13C NMR chemical shifts were expressed in parts per million downfield from CDCl3 (δ = 77.0) or CD3CN (δ = 1.39) as internal standards. 19F NMR chemical shifts were expressed in

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• ), which suggested that the radical process was probably involved in these transformations. Notably, no TEMPO-trapped product was detected by 19F NMR spectra of the crude reaction mixtures. On the basis of these results and literature studies [21][23][42][43][44][45][46][47], a plausible reaction mechanism

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• ) were added and the mixture was reacted at rt for 24 hours unless otherwise annotated. The yields are those of isolated products, and the dr was determined by 19F NMR analysis of the crude mixture. The results in parentheses are those of isolated products after the dissolution–filtration process: The

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• of TIPS-ethynyl-substituted BODIPY derivatives 3–6 were characterized by 1H and 19F NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallographic analysis. The solid-state structures of the diethynyl-substituted BODIPYs were unambiguously elucidated by X-ray diffraction analysis (3a

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• and 8 were proved by 1H, 13C, 15N, 19F and 77Se NMR and mass spectrometry. The composition of the products was confirmed by elemental analysis. Molecular ions of the synthesized compounds were observed in their mass spectra. Two doublets of the olefinic protons of the SCH=CHSe group with 3J = 6.3–6.6

• Information Supporting Information File 234: Experimental section and 1H, 13C, 15N, 19F and 77Se NMR spectra of all synthesized compounds. Acknowledgements The authors thank Baikal Analytical Center SB RAS for providing the instrumental equipment for structural investigations.

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• (Triaz)), 28.8 (s, 2 CHCH3 (Triaz)), 124.4 (s, CArH), 124.5 (s, CArH), 131.0 (s, CArH), 134.2 (s, CArH), 140.8 (s, CIV), 145.8 (s, CH (IPr)), 148.9 (s, CIV), 177.5 (s, Ccarbene); 19F{1H} NMR (282 MHz, CDCl3, 298 K) δ (ppm) −78.6 (s); anal. calcd for C33H41CuF3N3O3S: C, 58.26; H, 6.07; N, 6.18; found: C

• (IPr)), 31.3 (s, CCH3), 35.0 (s, CIV), 37.6 (s, CH3), 123.4 (s, CIV), 123.9 (s, CArH), 124.2 (s, C4 and C5), 124.4 (s, CArH), 126.6 (s, CArH), 129.4 (s, CArH), 130.5 (s, CArH), 130.9 (s, CArH), 134.3 (s, CIV), 144.8 (s, CIV), 145.2 (s, CIV), 152.0 (s, CIV), 152.8 (s, CIV), 179.4 (s, Ccarbene); 19F{1H

• (s, CHCH3 (Triaz)), 31.3 (s, CCH3), 35.0 (s, CIV), 37.8 (s, CH3), 123.6 (s, CIV), 124 (s, CArH), 126.2 (s, CArH), 129.0 (s, CArH), 131.1 (s, CArH), 134.3 (s, CIV), 145.0 (s, CIV), 149.2 (s, CIV), 153.4 (s, CIV); 19F{1H} NMR (282 MHz, CDCl3, 298 K) δ (ppm) −154.9 (s, BF4), −155.0 (s, BF4); anal. calcd

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• ), 19F NMR (376 MHz, CDCl3) δ 69.06; HRMS–APCI (m/z): [M + H]+ calcd for C38H35F2N2O2, 589.2644; found, 589.2661. The enantiomeric purity was confirmed by HPLC analysis: CHIRAL ART Cellulose-SB column, n-hexane/chloroform 95:5, 1.0 mL/min, 40 °C; (S)-2: tR = 9.86 min, (R)-2: tR = 21.29 min, UV detection