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

• peaks were detected in the fluorine spectra. The product yield calculated from the relative ratio of the product to the total integral area was comparable with the NMR yield calculated with hexafluorobenzene as internal standard in the high-field spectrometer (see Supporting Information File 1, Table S1

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• transformation was investigated as shown in Scheme 2. Various 1-arylethanol derivatives were firstly examined. Substrates bearing p-methyl (1b) or p-tert-butyl (1c) groups afforded the desired products 2b and 2c in moderate yields. Halogen substituents such as fluorine (1d) and chlorine (1e) atoms were tolerated

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

• acids B(C6F5)3 and B(C6H5)3 as electron acceptors, respectively [29]. B(C6F5)3 displays high chemical stability and Lewis acidity [30]. Moreover, its good solubility endows the possibility to form Lewis acid–base adducts in films by solution processing. The strong electron attraction of the fluorine

• spectrum (see Figure 9b), which were different from the same chemical environment of fluorine atoms in the original B(C6F5)3. To further explore the interaction of the Lewis acid–base pairs, Huang et al. added B(C6F5)3 to pyridine group-capped diketopyrrolopyrrole (DPP) molecules, i.e., DPPPy-Py-F (16

• , Figure 5) [29][39]. As illustrated in Figure 12a, BCF can narrow down the bandgap of the exciplex because of the stronger electrophilicity of the fluorine atoms. Similarly, Yamaguchi et al. used molecular modifications to introduce stronger electron donors to luminescent molecules and obtained stronger

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• bonds have been substituted with fluorine atoms. Within this family of molecules, perfluoroalkyl groups represent an industrially relevant moiety, capable of modifying the physicochemical properties of the scaffold that they are attached to. Such properties and a distinctive reactivity – or inert

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• observed in most of the compounds except for derivatives 4b, 4d, 4p, and 4u. All aromatic compounds showed resonances at δ = 6.50–8.00 ppm. Compounds 4b and 4c indicated the fluorine coupling effect on the aromatic protons. The carbaldehyde proton in compound 4h resonates at δ = 8.00 ppm, while compound 4k

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

• spectroscopy (Scheme 3h). Formation of 4a could have occurred from the direct reaction of the N–H nitrogen of 3a with NFSI, which would agree with the propensity for NFSI to react with some hard oxygen and nitrogen nucleophiles at the sulfur atom instead of at the fluorine atom [39][40]. Similarly, NFSI has

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• enaminone 15r, which was prepared in situ prior to cyclization. The pyrrolizine 19r was obtained within 90 seconds of microwave heating, and in 99% yield over the two steps. The rapidity of the condensation probably reflects both the inductive electron-withdrawing effect of fluorine and the minimal steric

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• example, when benzaldehydes substituted with fluorine or chlorine in the para-position were employed in catalytic reaction with anthranilamide (1a), the corresponding derivatives 3i,j were isolated in 58 and 69% yield, respectively. The rates of enantioselectivity for both reactions were lower and

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

• 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

• . Crystal structure of compound 3. Colour codes: carbon = grey, mitrogen = blue, oxygen = red, hydrogen = white. Crystal structure of 1H-1,2,3-triazole compound 5c: Colour codes: carbon = grey, nitrogen = blue, oxygen = red, fluorine = yellow, hydrogen = white. Crystal structures of compound 7b. Colour

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives. Keywords: functionalization; metathesis; nitrile oxide

• are considered as to be of type II, only a handful of literature data are available on the behavior of fluorine-containing olefins or perfluorinated alkenes. The incorporation of fluoroalkyl moieties (such as difluoromethyl, trifluoromethyl and perfluoroalkyl groups) into an organic molecule can often

• ) late-stage fluorination, when the fluorine atom is incorporated in the final step of the synthetic protocol (e.g., deoxofluorinations) or ii) application of various commercial fluorine-containing scaffolds (e.g., fluorine-containing amines, fluorine-containing alkenes etc.) [49][50][51][52][53][54][55

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• introduction of highly electronegative halides, such as fluorine or chlorine, on the phenyl ring afforded the substituted 9-methylanthracenes in lower yields. In addition, the method proposed by Lee and co-workers presented advantages that included shorter reaction times and milder reaction conditions [37

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. Mimicking the natural cellulose synthases machinery can be foreseen to provide synthetic Cellulose I. Some enzymes offer the flexibility to produce modified cellulose structures. Cellulose oligomers with fluorine substitution at C-2, C-3 or C-6 position were prepared by cellodextrin phosphorylases [78

• , fluorine, and carboxymethyl groups, prevented the formation of insoluble aggregates by disrupting hydrogen-bond networks. Dramatic differences in the conformation (e.g., radius of gyration and glycosidic bond conformation) and aggregation behaviour (i.e., crystallinity and solubility) were observed for

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• to oxidize ethylbenzene without significant loss of activity and metal leaching. The authors have suggested a mechanism for the reaction involving radical species bearing a benzylic carbon–vanadium bond. Fluorine presents unique features and may lead to essential changes in the structural and

• also been reported for the direct C(sp3)–H fluorination. Chen and co-workers [94] described a fluorination method employing Selectfluor as fluorine source and the commercially available V2O3 to give fluorine-containing compounds under mild conditions and with moderate to good yields (Scheme 10B,C). The

• /hemiacetal avoiding undesirable elimination to the enamine, or attack at other electrophilic sites in complex substrates. The presence of a fluorine source like diethylaminosulfur trifluoride (DAST) or the Lewis acid boron trifluoride diethyl etherate (BF3·OEt2) result in the formation of reactive iminium or

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

• Teruo Umemoto Yuhao Yang Gerald B. Hammond Department Chemistry, University of Louisville, Lousiville, Kentucky 40292, USA 10.3762/bjoc.17.123 Abstract This review deals with the historical development of all N-F fluorinating agents developed so far. The unique properties of fluorine make

• salt; fluoropyridinium salt; fluorosulfonimide; Introduction Fluorinated organic compounds occupy an important position in pharmaceuticals [1], agrochemicals [2], and materials [3]. Especially, in the first two areas, the presence of fluorine has attracted attention during the last decades. Nowadays

• , a considerable number of medicines [4][5] and agrochemicals [6] contain at least one fluorine atom in their structures. The fluorine atom has unique properties such as the highest electronegativity, extremely low polarization, strong C–F bonds, and the smallest size after a hydrogen atom [7]. Thus

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

• . Additionally, difluorination was observed with negligible amounts because the monofluorinated product is rendered more electronically deficient by the first fluorine atom. Based on an analysis by DFT calculations, the postulated reaction pathway of manganese-catalyzed C–H fluorination is described in Figure 1

• fluorine activation (see 22i–j), and the oxygen-containing natural terpenoid ambroxide was methylated at the methylene position next to the O atom on the tetrahydrofuran ring (see 22k). This manganese-catalyzed late-stage approach enables the direct methylation of unactivated C–H bonds with excellent site

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

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• profile with two transitions located at 386 and 400 nm. Methyl-substituted derivative 4b gave a slight red shift of 10 nm as compared to 4a. In contrast, fluorine and trifluoromethyl-substituted derivatives 4e and 4f show nearly the same emission. However, derivative 4g containing an electron-donating

• . Due to their low donating effect, the methyl group in product 4b induce an addition of yellow regions into the external phenyl rings. However, the electron-deficient fluorine atom in derivative 4e results in a decrease of the electron density of the tetrahydroacridine core and the external phenyl

• ground state from the optimized chemical structure of obtained molecules (Table 5). The calculated permanent dipole moments µ (D) have considerably increased values for 4f and 4g, which show significant changes in their experimental emission properties. The presence of six fluorine atoms induces a large

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• significant effect of the structure of the substituent at the nitrogen atom of the heterocycle on the OSC efficiency was also shown [29][30]. Thus, fluorine-substituted polymers 18a,b in the composition with PC61BM showed a PCE of only 0.9–1.4%, while an OSC based on ethoxylated derivative 19a was

• ][32][33]. In the course of further studies, the key influence of the nature of both the substituent at the nitrogen atom of isoindigo and at the bithiophene moiety on the OSC efficiency was confirmed. Thus, the introduction of fluorine atoms to thiophene rings in compound 22b leads to an increase in

• the above described study, Liu et al. demonstrated that this type of compounds is promising by means of introducing fluorine atoms into the thiophene ring [43]. The use of compound 29c (ratio of monomer units n/m = 2:1) as an acceptor component of the OSC made it possible to achieve one of the highest

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

• fluorine-containing organic molecules combined with the 1,4-quinone moiety can be considered as a challenging problem of current organic synthesis. Thus, the main goal of the present study was to check the course of [3 + 2]-cycloaddition reactions of electron-deficient CF3-substituted nitrile imines 7 with

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• -fluorinated analogs [25]. Considering the ever-growing demand for organofluorine compounds, the development of new methodologies that allow the incorporation of fluorine atoms into bioactive molecules is highly desired and will also be addressed herein. Recently, the use of indol-3-ylmethanols as

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• that the fluorine atom is too small to overly impact the overall packing. This structure has a planar conformation similar to that of 2,3,7,8,12,13,17,18-octaethylporphyrin [41]. Due to the high disorder in the crystal structure (the fluorine atom is disordered over the four meso positions) an accurate

• accounting of the interaction profile is not possible. However, there is the appearance of an F···H interaction between the ethyl groups and the fluorine atom which is projected throughout the crystal packing (Supporting Information File 1, Figure S57). In compounds 21 and 22, the number of β-halogen atoms

• mono- and di-halo-substituted porphyrins are only marginally different. The difference between the meso-free and fluorine derivatives is minimal. For the chloro to iodo derivatives, the disubstitution only exhibits a marginal decrease in the out-of-plane distortion relative to the mono-substitution

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

• enzymes [1][2][3][4][5][6][7]. The introduction of additional fluorine atoms into a monofluorinated carbohydrate is an attractive way of modulating the binding affinity and pharmacokinetic properties of fluorinated glycomimetics. Hydrophobic segments incorporating multiple C–F bonds could (1) reduce the

• biomedical applications due to their ability to inhibit the glycan and glycosaminoglycan biosynthesis [34][35][36][37]. The fluorine substituent has typically been introduced into these GlcNAc and GalNAc analogues using nucleophilic fluorination. The primary position (C6 hydroxy group) was fluorinated by

• DAST [22][25][26][30][35], or reaction of C3/C4 methanesulfonate or trifluoromethanesulfonate esters with a source of nucleophilic fluorine, such as TBAF or KF [22][25][34]. Although these fluorinations usually proceeded with inversion of configuration, the acetylated 3-fluoro-GlcNAc analogue was most

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• ]. Longer reaction times and lower temperatures were used to improve the first step that resulted in very good yields. Recently, Xiao et al. used this method for the synthesis of 13 new fluorine-containing proguanil derivatives which were found to be more active than proguanil in five human cancerous cell

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

• acids (ANA) are analogs of RNA where the hydroxy group at C2' is inverted (Figure 1G). In fluoroarabino nucleic acids (FANA) this C2' hydroxy group is replaced by fluorine. Arabino- and fluoroarabino nucleosides have demonstrated anticancer and antiviral activities (as reviewed in [173]). β-ᴅ

• , the natural DNA sequence had a half-life of 1 min [202]. The incorporation of fluorine at the C4' position has long constituted a challenge owing to the instability of the glycosidic bond in the resulting nucleosides. This modification is desirable due to its involvement in the mode of action of the

• natural antibiotic nucleocidin [203][205]. Damha reasoned that the incorporation of fluorine at both C2' and C4' could lead to a stable nucleoside due to the glycosidic bond stabilization brought about by 2'-fluorination [206] which turned out to be correct after successful isolation of both 2',4'-diF-rU

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• gram scale. The introduced bromine atom can be converted into fluorine and allyl groups. Keywords: bromination; C–H transformation; hydrogen abstraction; manganese; radical; Introduction Organic halides are versatile precursors for various synthetic protocols and are frequently used to introduce a

• reaction proceeded regioselectively at the methine C(sp3)–H bond of isoamyl benzoate (1b) to give 2b in 64% yield. Isoamyl benzoates bearing halogen atoms, such as fluorine, chlorine, or bromine, on the phenyl ring were also suitable substrates and gave C(sp3)–H brominated products 2c–e in 49–60% yields

• functionalized upon the introduction of other functional groups, such as fluorine and allyl groups. We hope that this C(sp3)–H bromination reaction will become a useful method to synthesize organic compounds with bromine atom(s). Several examples of C(sp3)–H halogenation. Substrate scope. a80 °C. b45 min. c4 h