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Search for "fluorination" in Full Text gives 156 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting
Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45
- incorporating the new F-lipopeptides were determined and compared to those of reference MBs of similar phospholipid composition. Results and Discussion Synthesis and characterization of the lipid–peptide conjugates Since the degree of fluorination of the hydrophobic chains of the lipid conditions the extent of
- , reflecting a progressive adsorption at the interface, then reached a plateau, and stabilized at the equilibrium surface pressure (πeq). The adsorption kinetics demonstrate that the F-lipopeptides formed stable monolayers at the interface. The πeq values increased with the degree of fluorination of the F
- , reflecting the insertion in the DPPC monolayer. The higher the degree of fluorination, the higher the amount inserted, with a maximal efficiency observed for lipopeptide 3 (C8F17). However, the behavior of the F-lipopeptide 2 with an odd number of carbon atoms (C7F15) is closer to that of 1 (C6F13) than to
Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement
Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40
- properties. These factors may translate into an altered structure and stability of a protein containing a fluorinated fragment. What consequences fluorination would have regarding the fitness and survival of the organism relying on fluorine-containing proteins remains an open question. In this context, the
- compared to proline (Figure 5) [19]. Although, the difference is small, it may have an impact on the overall features of the peptides and proteins that rely on polarity. 2.4 Proline puckering In addition to the general impact of fluorination, there are some properties specifically attributed to the proline
- folding, thereby stabilizing or destabilizing particular secondary structure folds. Fluorination creates a pucker bias due to orbital interactions of the carbon–fluorine bond within the molecule, known as the gauche-effect [50]. The parent proline structure has a negligible energetic difference between
Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system
Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39
- of fluorine(s) into organic molecules usually leads to significant changes in the chemical and physicochemical properties of the original compounds [5][6]. Hence, the fluorination and related fluoro-functionalization of drug candidates are powerful strategies in drug design to appropriately bias
- cost of target compounds [11][12][13][14][15]. Thus, the development of low-cost and straightforward chemical synthetic technologies, including fluorination and trifluoromethylation, are matters of considerable importance to pharmaceutical and agrochemical industries. Fluoroform (HCF3, HFC-23) is an
The preparation and properties of 1,1-difluorocyclopropane derivatives
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
- ) were successful. Therefore, alternative methods such as intramolecular cyclizations, exchange fluorination, and transformation of functional groups in fluorinated rings have been developed in order to provide access to fluorinated cyclopropanes with electron-withdrawing substituents. 1.1
Decarboxylative trifluoromethylthiolation of pyridylacetates
Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23
- lithium pyridylacetates undergo decarboxylative fluorination upon treatment with an electrophilic fluorination reagent to afford fluoromethylpyridines under catalyst-free conditions. Furthermore, we demonstrated the one-pot synthesis of fluoromethylpyridines from methyl pyridylacetates by saponification
- of methyl esters and subsequent decarboxylative fluorination (Scheme 1a) [21]. Herein, we describe the application of this method to decarboxylative trifluoromethylthiolation with an electrophilic trifluoromethylthiolation reagent (Scheme 1b) [22], which enables easy installation of the
- -trifluoromethylthiolated product 9 in 36% yield, along with 6% yield of disubstituted product 10 (Scheme 4). Increasing the amount of 6 did not improve the yield of products 9 and 10 significantly. Based on the abovementioned results and our previous study on decarboxylative fluorination [21], we propose a plausible
Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding
Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13
- of iodofluorobenzene derivatives with nitro-cyanostilbenes is reported. The systematic variation of the fluorination degree and pattern indicates the relevance of the halogen bond strength for the induction of liquid crystalline properties. The modular self-assembly approach enables the efficient
- fluoroiodoazobenzenes with varying fluorination degree at the iodobenzene moiety was used to investigate the impact of halogen bonding on the properties of the assemblies. Since cyanostilbene molecules are known to show aggregation-induced emission (AIE) behaviour the photophysical properties of the resulting
- induction of liquid crystallinity in our assemblies, we synthesised a series of azo compounds with decreasing fluorination degree at the halogen bond donating iodobenzene [12]. Reducing the number of the fluorine atoms at the halogen bond donating moiety lowers the polarisation of the iodine atom and thus
Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols
Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8
- fluoride species, which can subsequently react with the alcohol, delivering thionoester 4. β-Fluoride elimination is a known decomposition pathway of −SCF3 and has even been exploited in synthetic trifluoromethylthiolation and fluorination processes [32][33][34]. The formation of the side-product 4a could
Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction
Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260
- typically introduced into a saturated cycle by nucleophilic fluorination reactions [10][11][12][13][14][15][16][17]. For compounds bearing gem-difluorinated fragments, an alternative pathway based on the construction of the cycle from building blocks may be considered [18]. However, the latter frequently
Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD®/Olah’s reagent under solvent-free conditions
Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254
- and not as fluorination of acyl fluorides. Thus, the acyl fluoride moiety is commonly sacrificed as a “leaving group” in reactions. On the other hand, the transformation to CF3 derivatives from carboxylic acids are traditionally examined. In 1960, Engelhardt [27] performed the deoxyfluorination of
Controlled decomposition of SF6 by electrochemical reduction
Beilstein J. Org. Chem. 2020, 16, 2948–2953, doi:10.3762/bjoc.16.244
- degradation of SF6 [17][18]. Other elegant approaches have described the use of SF6 as precursor of reagent for fluorination or pentafluorosulfanylation. Very interestingly, the photochemical activation of this gas was described and allowed the in situ transformation of alcohols into alkyl fluorides [19][20
Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose
Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237
- approach using Et3N·3HF as an alternative to the DAST reagent. We controlled the stereochemistry of the nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-4-O-triflate-β-ᴅ-talopyranose using Et3N·3HF or in situ generated Et3N·1HF. The influence of the fluorine atom at C2 on reactivity
- various deoxyfluorination reaction conditions. In our specific case, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 with the use of Et3N·3HF. As proposed by the group of Linclau [20], we support the involvement of an oxiranium intermediate (results reinforced by
- elimination byproduct. These results suggest that addition of Et3N dictates the selectivity for the C4 fluorination. With the optimized conditions in hand, we investigated the use of other triflate analogues (Figure 3a). Under optimized conditions (Table 2, entry 2), triflate analogues 16–18 [19] gave
Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity
Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216
- . Stereoselective fluorination is an emerging strategy for controlling the conformations of organic molecules. The highly polarized C–F bond tends to align in predictable ways with adjacent functional groups, due to a combination of hyperconjugative and/or dipolar interactions [18][19][20][21]. This knowledge led
- products. We were forced to conclude that the rather complex structure of 3 was incompatible with the Jacobsen catalytic system. Since the one-step difluorination method (Scheme 1) was unsuccessful, we decided to pursue a stepwise fluorination approach [26][27] (Scheme 2). Thus, the allylic alcohol 7 [28
- obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the
Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination
Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213
- ACF itself consists of the fluorination of AlCl3 by chlorofluoroalkanes [40][41]. Nevertheless, in C6D6, the formation of 5 and 6 and the Friedel–Crafts product CF2=CHCH2C6D5 (9) was observed from 14. Based on these findings, a general scheme can be drafted to illustrate the sequential generation of
Synthesis of novel fluorinated building blocks via halofluorination and related reactions
Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208
- cyclic olefins, such as diesters, imides, and lactams with varied functionalization patterns and different structural architectures is described. The synthetic methodologies were based on electrophilic activation through halonium ions of the ring olefin bonds, followed by nucleophilic fluorination with
- transformation, and COOH→CF3 transformation), is also an important nucleophilic fluorination method [2][3][4][5][10][11][18]. The synthesis of fluorinated compounds via deoxyfluorination [21][22][23][24][25][26][27][28][29][30] or utilizing sulfur fluoride deoxyfluorinating reagents [31][32] is a highlighted
Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction
Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200
- expensive and time-consuming procedure [2]. Fluorination is a common strategy employed as part of the optimization process during the design of new chemical compounds, which includes the modulation of a variety of properties such as lipophilicity, biological half-life, and biosorption [3][4]. This role
- helps in explaining the expressive amount of fluorine-containing agrochemical candidates (around 30%) as well as pharmaceuticals (around 20%) [5][6]. In this sense, the chemistry of fluorine-containing compounds has been extensively investigated in order to better understand the effects of fluorination
- and their unusual physicochemical properties. Lastly, Müller [11] explained that these features along with fluorine’s strict monovalent binding mode and little polarizability, when covalently bound, guarantee fluorination the well-known ability of modulating physicochemical properties. Although the
Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis
Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183
- fluorination methods, of which direct C–H fluorination is among the most powerful. Despite the challenges and limitations associated with the direct fluorination of unactivated C–H bonds, appreciable advancements in manipulating the selectivity and reactivity have been made, especially via transition metal
- catalysis and photochemistry. Where transition metal catalysis provides one strategy for C–H bond activation, transition-metal-free photochemical C–H fluorination can provide a complementary selectivity via a radical mechanism that proceeds under milder conditions than thermal radical activation methods
- review, we highlight photosensitized C–H fluorination as a recent strategy for the direct and remote activation of C–H (especially C(sp3)–H) bonds. To guide the readers, we present the developing mechanistic understandings of these reactions and exemplify concepts to assist the future planning of
Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups
Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182
- Nantes, France Medicinal Chemistry, Oncology R&D, AstraZeneca, Cambridge CB4 0WG, UK 10.3762/bjoc.16.182 Abstract A systematic comparison of lipophilicity modulations upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl substituents, at a single carbon atom, is provided using directly comparable
- , and easily accessible model compounds. In addition, comparison with relevant linear chain derivatives is provided, as well as lipophilicity changes occurring upon chain extension of acyclic precursors to give cyclopropyl containing compounds. For the compounds investigated, fluorination of the
- isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent. Keywords: aliphatic fluorination; cyclopropane; isopropyl; isostere; lipophilicity; oxetane; Introduction The introduction of small alkyl groups onto bioactive compounds as space filling
Synthesis of 6,13-difluoropentacene
Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181
- significant effect on the molecular shape, is fluorination [5]. Suzuki et al. showed in 2004 the strong effect of perfluorination on the electronic properties [6]. While unsubstituted pentacene (1, PEN, Figure 1) is known to be a p-type semiconductor, the perfluorinated counterpart perfluoropentacene (2, PFP
- ) showed an n-type behavior. In their synthesis and structural as well as electronic characterization of F4PEN 3, Bettinger et al. showed that the electronic properties of pentacenes are not a simple linear function of the degree of fluorination [7][8]. They reported that the fluorination in the 2,3,9,10
- herringbone structure of 1–3. Here, the synthesis and characterization of 6,13-difluoropentacene (5, F2PEN) is reported. Since the central ring of pentacenes is known to be a weak spot (because of light-induced dimerization or oxidation) [2] the effects of fluorination in these positions are of interest
Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination
Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163
- alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6
- previously tested the reactivity of 8 in the intermolecular aldol addition to ethyl glyoxalate [62]. As these attempts met with failure, we have turned our attention to enantioselective fluorination reactions [63][64][65]. Specifically, we decided to explore the enantioselective electrophilic fluorination of
- was successfully utilized for the synthesis of several bioactive molecules [79][80][81]. Herein we present its adaptation for the enantioselective fluorination of 2-oxo-aldehyde-derived Ugi adducts 8 leading to the installment of a fluorine-bound quaternary stereocenter at the peptidyl position. It
On the hydrolysis of diethyl 2-(perfluorophenyl)malonate
Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153
- range by fluorination (directly or indirectly) of initial organic molecules. In the ongoing project, we are interested in synthesizing 2-(perfluorophenyl)malonic acid (2, Figure 1) as a new ligand for the preparation of 3d and 4f heterometallic coordination compounds. Results and Discussion To our
Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines
Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151
- fluorination usually increases polarity of a molecule due the newly introduced polar C–F bond. A CF3 group introduces a dipole of a similar size (see Figure 2), however, due to its high molar volume it increases the hydrophobicity of a molecule [75]. The overall outcome may appear paradoxical: a CF3 group can
- compounds 5 and 6 follow generally similar chiral bias to 3 and 4. The pKa data for the free amino acids shows that there is an identical reduction of the pKa values from fluorination (Figure 10B and C). It was then found that neither the side-chain conformation markers (J coupling at 2-CH) nor the trans
- between the diastereomeric species. Indeed, this conclusion was further corroborated by the rotation barrier data, which showed higher Δwater/benzene for the less lipophilic diastereomer, 6 (Table 4). Overall, the effects from fluorination in both diastereomeric compounds, 5 and 6, were found to be weak
Pauson–Khand reaction of fluorinated compounds
Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138
- most profound influence [10][11][12]. Regarding the development of new synthetic methodologies for the preparation of such molecules, these can be divided in two main categories: fluorination reactions [13][14][15][16] and the use of fluorinated building blocks [17]. The difference between them is that
Fluorohydration of alkynes via I(I)/I(III) catalysis
Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135
- suppressed catalysis. The prerequisite for this substructure was established by molecular editing and was complemented with a physical organic investigation of possible determinants. Keywords: α-fluoroketone; alkyne; fluorination; hypervalent iodine; organocatalysis; Introduction The venerable role of
- non-covalent interactions [8][9][10]. These collective attributes render fluorination a valuable strategy in drug discovery [11] and agrochemical development [12]. In the conception of enabling fluorination technologies, the α-fluorocarbonyl motif has emerged as a prominent target scaffold [13
- ]. Remarkable advances in the direct fluorination (F2/N2) of carbonyl compounds by Sandford and co-workers [14][15] are noteworthy in this regard, and mitigate the expense and poor atom economy associated with stoichiometric approaches. Moreover, this substructure provides a versatile entry point for subsequent
Heterogeneous photocatalysis in flow chemical reactors
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
Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117
- heteroaromatic systems, especially those comprising two heteroatoms such as pyrazoles [28][29], isoxazoles [30], and thiazoles [31][32]. Recently, we reported the selective fluorination of isoxazoles, to give monofluorinated isoxazoles 3 or trifluorinated isoxazolines 4 in moderate to good yields (Scheme 1) [33
- fluorinated diketone, 2-fluoro-1,3-diphenylpropane-1,3-dione (7a), the corresponding enaminoketone 8a was obtained in only low yield (Scheme 4, entry 4) and we did not attempt the conversion of 8a towards the α-fluorinated boron ketoiminate 9a. Next, we attempted the selective fluorination of 6b to obtain the
- desired fluorinated analog 9b. However, in the synthesis of F-BKIs through the selective fluorination of the corresponding BKIs, the use of 1 equiv of Selectfluor did not give any product and performing the reaction with excess amounts of Selectfluor gave rise to the corresponding α,α-difluorinated
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