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Search for "fluorination" in Full Text gives 156 result(s) in Beilstein Journal of Organic Chemistry.
Halogen-containing thiazole orange analogues – new fluorogenic DNA stains
Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283
- chromophores have been studied by Armitage and co-workers [42][43]. According to these studies the fluorination of the symmetrical [42] and unsymmetrical [43] cyanine dyes results in reduced aggregation and significantly improved the photostability and photophysical properties of the dyes. The authors [43
The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers
Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280
- confirmed the presence of a primary fluoride. Hence, non-acidic epoxide opening conditions were investigated to circumvent the rearrangement (Scheme 4). Both the use of Bu4NH2F3 [18] and of the TBAF/KHF2 reagent combination [22] were successful (56% and 64%, respectively). While subsequent fluorination
Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion
Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279
- , and the aspartate protease pepsin. Results and Discussion Peptide design and structure To elucidate the impact of fluorination on proteolytic stability we previously designed the peptide FA (Figure 1b) that comprises the substrate specificities of α-chymotrypsin and pepsin [39][40]. Consequently, the
- hydrophobic than their hydrocarbon analogues [44][45]. Furthermore, fluorine substitution has been shown to polarize neighboring C–H bonds (here the γ-hydrogens) that could affect noncovalent interactions [9][11]. Since the amino acids used here (Figure 1a) differ in their degree of fluorination, spatial
- ’ substituted peptides, along with the control peptide FA, are almost or completely digested, P2’-HfLeuFA is still present to about 76%. In this case fluorination leads to protection against proteolysis by pepsin. Hfleu is obviously not well accommodated in this position. As already observed for position P1
Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds
Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277
- the singlet at 2.34 ppm belongs to the methyl group. This is consistent with known data on fluorinated diketones: stability of the enol tautomer increases with the degree of fluorination [29][30]. Apparently this could explain the difference in ratios of tautomers in addition products of structurally
The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands
Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276
- attracting increasing interest as around 100 peptides are on the pharmaceutical market [2]. Peptide fluorination has appeared as a general and effective strategy to enhance the stability against enzymatic, chemical and thermal denaturation while generally retaining the original structure and biological
Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres
Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262
- ]-Gly isosteres with control of the stereochemistry at the side chain will be discussed in this section. In particular, olefination reaction, defluorinative reduction of 3,3-difluoropropene derivatives and electrophilic fluorination of alkenylstannanes are presented. Pannecoucke’s group described the
- final saponification gave the monofluoroalkene-based dipeptide isostere 61. Finally, Fürstner’s group developed the silver-mediated fluorination of functionalized alkenylstannanes to access monofluoroalkenes [42]. Hydrostannation of the N-protected ynamines 62 followed by electrophilic fluorination with
- Selectfluor gave the corresponding (Z)-monofluoroalkenes 64 in good yields (Table 2). The reported results showed that the methodology was suitable to replace an amide bond and could be used in late-stage fluorination to access monofluoroalkene-based dipeptide isosteres. Xaa-ψ[CF=CH]-Xaa The preparation of
Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones
Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259
- modern drug discovery and development area [9][10]. As a result of intensive research efforts over the last decades, efficient fluorination and fluoroalkylation methods have emerged to prepare previously challenging molecules decorated with fluorine atoms or fluorinated groups which make them practically
Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides
Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258
- past decade, investigations mainly focused on direct fluorination or fluoroalkylation of aromatics [1][2][3][4][5]. Fluoroalkylated alkenes are a kind of important fluorinated structural motifs and have wide applications in medicinal chemistry and advanced functional materials [6][7][8][9]. However
Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts
Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254
- accessible from amino acids, are widely used in these kinds of reactions [13][14][15][16][17][18]. More recent examples demonstrate the applicability in various reactions like diastereoselective α-fluorination [19], total syntheses [20][21], cross-dehydrogenative couplings [22], selectivity-reversed Friedel
Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241
- nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule’s polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage
- fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are
- used to model the effects of fluorination on the lipophilicity, hydrolytic stability and on conformational properties. The conformational impact of the 2,2-difluoromethyl ester on several neutral and charged oligopeptides was also investigated. Our results demonstrate that partially fluorinated esters
Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence
Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233
- -amino ester stereo- and regioisomers, derived from unsaturated cyclic β-amino acids is described. The nucleophilic fluorinations involving hydroxy–fluorine exchange of some highly functionalized alicyclic diol derivatives have been carried out in view of selective fluorination, investigating substrate
- controlled efficient fluorination procedures. This high interest is clearly demonstrated by the number of various published papers on the field, and related recent comprehensive reviews [3][4][5][6][7][8][9][10][11][12]. The nucleophilic fluorination with commercially available organic fluorinating agents
- fluorination based on hydroxy–fluorine interconversion seems to be an eloquent, simple and efficient procedure for the creation of a certain fluorinated organic molecule, regio- and stereoselectivity, stereocontrol and substrate influence remain a challenge in the case of highly functionalized frameworks
Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis
Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228
- describe the synthesis of δ-amino acids that contain three vicinal C–F bonds positioned along the backbone. The ultimately successful synthetic approach emerged through the investigation of several methods based on both electrophilic and nucleophilic fluorination chemistry. We show that different
- the repeating (CHF)n motif within the target molecule via an iterative synthetic approach (Scheme 1, boxed). We reasoned that an aldehyde such as 7 could undergo electrophilic fluorination, mediated by a chiral organocatalyst [18][19][20], to generate the fluorinated aldehyde 8 as a single
- stereoisomer. Then, if the carbon chain of 8 could be extended by one atom to give the homologated aldehyde 9, fluorination could be repeated and the cycle could continue until the desired number of fluorine atoms was installed. This hypothetical approach had several attractions, including (i) the flexibility
One-pot multistep mechanochemical synthesis of fluorinated pyrazolones
Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189
- has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields. Keywords: fluorination; heterocycles
- designed a 2-step reaction related to our recent work on liquid assisted grinding effects of the fluorination of 1,3-dicarbonyl compounds, in which the dicarbonyl will initially form a pyrazolone in the first reaction prior to undergoing difluorination in the second step (Scheme 1) [17]. Notably this
- the hydrazine is slow, meaning that the nucleophilicity is greatly retarded compared to lower acid loadings. Nonetheless, considering that the subsequent fluorination step should proceed optimally under basic conditions [17], the lowest amount of acid which also provided a good yield was thus chosen
Mechanochemical synthesis of small organic molecules
Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186
- poor selectivity in mono- or polybrominations (Scheme 26). They have also explored halogenations of 1,3-dicarbonyl compounds to obtain dihalo derivatives in excellent yield [100]. In 2016, Browne and co-workers reported selective mechanochemical fluorination of 1,3-dicarbonyl compounds using
- reaction of electron-rich arenes [88][98]. Mechanochemical aryl halogenation reaction using trihaloisocyanuric acids [100]. Mechanochemical fluorination reaction by LAG method [102]. Mechanochemical Ugi reaction [116]. Mechanochemical Passerine reaction [116]. Mechanochemical synthesis of α-aminonitriles
Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles
Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170
- most important field of application of this catalytic principle. Based on several highly spectacular recent reports, we thus wish to discuss some of the most important achievements in this field within the context of this review. Keywords: amination; chlorination; fluorination; hydroxylation
- , enantiospecific nucleophilic displacement reactions [66][67]. α-Fluorinations The stereoselective electrophilic α-fluorination of carbonyl compounds became a thoroughly investigated field over the course of the last 15 years [68][69][70][71][72]. A variety of different catalytic approaches, either relying on the
- nucleophiles dates back to 2002, when Kim and Park described the first use of cinchona alkaloid-based quaternary ammonium salts A (i.e., derivative A1) for the enantioselective α-fluorination of β-ketoesters 1 by using N-fluorobenzenesulfonimide (NFSI, 2) as the fluoride-transfer reagent [73] (Scheme 2). By
Strategies toward protecting group-free glycosylation through selective activation of the anomeric center
Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123
- from β-D-glucose pentaacetate, α-fluoro-D-glucose can be obtained with the key fluorination effected by using Olah’s reagent. The appeal of this procedure is obvious. It is an operationally simple and stereo- and regioselective method to obtain tri- and oligosaccharides containing a sucrose moiety
Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications
Beilstein J. Org. Chem. 2017, 13, 863–873, doi:10.3762/bjoc.13.87
- analogue P2, the LUMO energy decreased by 0.10 eV compared to P1 (indicating an increased electron affinity upon fluorination) and the corresponding HOMO level stabilized by 0.24 eV. Hence, both molecular energy levels could be tailored by the introduction of fluorine. In the case of P3, the HOMO level
- on the optoelectronics and photovoltaic performances has been demonstrated. It was observed that the incorporation of fluorine, a strong electron-withdrawing group, resulted in deeper HOMO energy levels for the polymer P2 as compared to polymer P1. The fluorination also enhances the intramolecular
- interaction between the polymer chains, which is reflected in the higher hole mobility of P2 over P1. Though the photovoltaic parameter values are very low for these polymers, it was observed that fluorination could increase the overall device performance by ≈110%. The effect of increased planarity along the
Synthesis of ribavirin 2’-Me-C-nucleoside analogues
Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74
- decrease in the order: H5’b-H4’ > CH3 > H1’. The selective excitation of H1’ in 13a led to nOes with decreasing intensities in the order: H5’b-H4’ > CH3 > H3’, whereas for 13b the order was CH3 > H5’b-H4’. This second series of nOes confirms that CH3 is closer to H1’ in 13b than in 13a. The fluorination of
- fluorinated analogue 3 required a more complicated pathway. This included the selective protection of the 3’,5’ positions, the stereoselective methylation and the fluorination of the 2’ position. The synthesized compounds are currently investigated for their antiviral activities. Experimental Experimental
- . Structural study of isomeric compounds 13. Synthesis of 5-(2’-C-methyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxamide (2). Synthesis of the 2’-keto derivatives 12a/12b. Fluorination of ethyl 1-benzyl-4-(2’-C-methyl-3’,5’-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl)-1,2,3-triazole-5-carboxylate
Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif
Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72
- then applied to diastereoisomers 8b and 8c as illustrated in Scheme 3. Fluorination of the isomer mixture 8b/8c with Et3N·3HF at 140 °C gave 9b and the racemic 9c as an inseparable mixture. Triflation of this product mixture generated 10b and 10c, isomeric products which could now be separated by
- chromatography. Finally fluorination of 10b and 10c in separate reactions with Et3N·3HF at 120 °C furnished nitrile 11b (51% yield) and 11c (31% yield) respectively. The structure and stereochemistry of both products were unambiguously confirmed by X-ray structure analysis (Scheme 3). Reduction of 11b with
Synthesis of 1-indanones with a broad range of biological activity
Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48
- derivatives 123 via the Nazarov cyclization followed by electrophilic fluorination, has been described in 2007 by Ma et al. [65]. This reaction was catalyzed by Cu(II) triflate and proceeded in the presence of N-fluorobenzenesulfonimide (NFSI) 122 as a fluorinating reagent (Scheme 39). Scientists are
Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring
Beilstein J. Org. Chem. 2016, 12, 2823–2827, doi:10.3762/bjoc.12.281
- also rendered fluorine containing compounds important in the development of organic materials such as liquid crystals [8][9]. Strategic fluorination can add polarity to a molecule, however, such compounds do not generally increase in their hydrophilic capacity, thus selective fluorination leads to
- polar-hydrophobic properties [10]. Although selective mono-fluorination and CF3 incorporation have had wide currency, the difluoromethylene (CF2) motif has received relatively less attention despite possessing unique properties [11][12][13][14]. For example CH2F2 shows the highest molecular dipole (1.97
- byproducts. The reaction of ketones 5a–c with 1,2-ethanedithiol in the presence of catalytic BF3·OEt2 afforded the corresponding bis-dithianes 6a–c in moderate to good yields [26] (Scheme 2). The reaction of diketone 5c also afforded the monoderivatised ketone 9 as a minor product. Direct fluorination of
Comparing blends and blocks: Synthesis of partially fluorinated diblock polythiophene copolymers to investigate the thermal stability of optical and morphological properties
Beilstein J. Org. Chem. 2016, 12, 2150–2163, doi:10.3762/bjoc.12.205
- blends. Here we explore the impact of backbone fluorination in block copolymers of poly(3-octyl-4-fluorothiophene)s and poly(3-octylthiophene) (F-P3OT-b-P3OT). Two block co-polymers with varying block lengths were prepared via sequential monomer addition under Kumada catalyst transfer polymerisation
- , suggesting that such materials may be interesting for enhanced thermal stability of organic photovoltaic active layers based on similar systems. Keywords: conjugated block-copolymer synthesis; fluorination; microphase stabilization; polythiophene; temperature-dependent Raman spectroscopy; Introduction With
- fluorination which increases backbone rigidity [41][42]. As an initial exploration, this contribution presents the synthesis and purification of two block copolymers of poly(3-octylthiophene) (P3OT) and poly(3-fluoro-4-octylthiophene) (F-P3OT) with different relative block lengths. The thermal behavior of the
Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics
Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182
- Homoleptic zinc(II) complexes of di(phenylacetylene)azadipyrromethene (e.g., Zn(WS3)2) are potential non-fullerene electron acceptors for organic photovoltaics. To tune their properties, fluorination of Zn(WS3)2 at various positions was investigated. Three fluorinated azadipyrromethene-based ligands were
- chelated with zinc(II) and BF2+ and the optical and electrochemical properties were studied. Fluorination had little effect on the optical properties of both the zinc(II) and BF2+ complexes, with λmax in solution around 755 nm and 785 nm, and high molar absorptivities of 100 × 103 M−1cm−1 and 50 × 103 M
- −1cm−1, respectively. Fluorination of Zn(WS3)2 raised the oxidation potentials by 0.04 V to 0.10 V, and the reduction potentials by 0.01 V to 0.10 V, depending on the position and type of substitution. The largest change was observed for fluorine substitution at the proximal phenyl groups and CF3
Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine
Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75
- 75 °C (conditions used for fluorination of 11), or in dichloromethane at rt was attempted. Disappointingly, only unreacted 15 was recovered. A very slow formation of several unidentified fluorine-containing compounds (19F NMR) was observed on prolonged reaction times. Oxidative debenzylation of 19
- analysis. Since fluorination of 12 with DAST failed to introduce fluorine at C-4β due to formation of orthoester 25, the reaction of 1,6:2,3-dianhydro-β-D-talopyranose 14 with DAST was utilized to give 1,6:2,3-dianhydro-4-deoxy-4-fluoro-β-D-talopyranose (30) with retention of the configuration at C-4 [39
- reported in [20]. Our synthesis of 5 is more practical (55% from 10 in 3 steps) than the earlier preparations which were reported troublesome owing to low yields (28% and 10%, respectively) of the key fluorination step [18][20]. For the remaining fluoro derivatives of 1,6-anhydro-2-azidohexopyranoses
A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids
Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64
- may undergo stereoselective trap by H2O to form alcohol epimers 2; these may then undergo a stereospecific SN2 reaction to form fluoride epimers 8; c) the fluorination and/or hydroxylation of cation 10, forming fluoride epimers 8 and alcohol epimers 2, respectively, may be reversible. This has several
- effects: firstly, reversible hydroxylation means that alcohol epimers 2 may convert to fluoride epimers 8 via cation 10 (pathway (a)); secondly, reversible fluorination and/or hydroxylation means that the diastereoselectivity of formation and/or 2 may be governed by product stability and not inherent
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