Sulfur Trifluoride Research Articles

Synthesis of Long‐Chain Polyamides via Main‐Chain Modification of Polyethyleneketones

AbstractLong‐chain polyamides (polyethyleneamides) were prepared from polyethylenes bearing in‐chain carbonyl groups (polyethyleneketones) by the oxime formation and successive Beckmann rearrangement. (Diethylamino)sulfur trifluoride (DAST) was utilized as a promoter, which allowed mild conversion of the oxime group in spite of low solubility of the polymers. The polyethyleneamide exhibited different tensile property compared to a commercial HDPE.

(Diethylamino)sulfur trifluoride (DAST)-mediated oxidation of benzylic alcohols and amines to carbonyl compounds

We report an efficient protocol for oxidation of primary/secondary benzyl alcohols and benzylamines to produce corresponding aldehydes or ketones. Our unified method involves the use of commercially available (diethylamino)sulfur trifluoride (DAST) as a reagent combined with DMSO as solvent and oxidant. The reaction provided corresponding carbonyl compounds in good to excellent yields with high purity and in short reaction times.

Synthesis of Long-Chain Polyamides via Main-Chain Modification of Polyethyleneketones.

Long-chain polyamides (polyethyleneamides) were prepared from polyethylenes bearing in-chain carbonyl groups (polyethyleneketones) by the oxime formation and successive Beckmann rearrangement. (Diethylamino)sulfur trifluoride (DAST) was utilized as a promoter, which allowed mild conversion of the oxime group in spite of low solubility of the polymers. The polyethyleneamide exhibited different tensile property compared to a commercial HDPE.

Fluorination of vanadates with organic fluorinating agents

The organic fluorinating agents [bis(2-methoxyethyl)amino]sulfur trifluoride (Deoxo-fluor®), diethylaminosulfur trifluoride (DAST), and N-fluorobenzenesulfonimide (NFSI) were used to inspect the efficiency of fluorination of monovanadate, HxVO4(3−x)− (V1), and decavanadate, HxV10O28(6−x)− (V10), in solution by 51V NMR spectroscopy. It was observed that either VOF4− or VO2F2− can be generated in acetonitrile solutions at room temperature after one hour selectively for HxVO4(3−x)−, while HxV10O28(6−x)− is more sensitive towards reduction and only NFSI can be used to generate VOF4−. The differences in reactivity can be attributed to the electrophilicity of fluorine in Deoxo-fluor® and DAST, and its nucleophilicity in NFSI. Tetrabutylammonium fluoride, triethylamine trifluoride, and hydrogen fluoride–pyridine adduct were also used under the same conditions for comparison of the efficiency and selectivity of fluorination. It was observed that only HF.pyridine provided a complete transformation of V1 and V10 into VOF4−. The pilot experiments introduced in this work are the first example of fluorination of polyoxometalates with organic fluorination agents and other less commonly used fluorides with organic cations and show their great potential in the synthesis of polyoxometalates with fluorido ligand.

Synthesis of Morita–Baylis–Hillman-fluorides using 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine

Morita–Baylis–Hillman (MBH)-fluorides are valuable platforms for asymmetric allylic substitution reactions. However, the preparation of MBH-fluorides requires the use of an explosive fluorinating reagent, namely (diethylamino)sulfur trifluoride (DAST). Thus, we herein report a safe, alternative method for the preparation of MBH-fluorides via the deoxyfluorination of MBH-alcohols using 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA). Accordingly, a variety of MBH-alcohols were smoothly converted to their corresponding MBH-fluorides in moderate to good yields without the requirement for an activator. This fluorination reaction was found to proceed via an SN1 process involving a stable allylic cation intermediate.

4-Fluoro-Threonine: From Diastereoselective Synthesis to pH-Dependent Conformational Equilibrium in Aqueous Solution.

4-Fluoro-threonine, the only fluoro amino acid of natural origin discovered so far, is an interesting target for both synthetic and theoretical investigations. In this work, we lay the foundation for spectroscopic characterization of 4-fluoro-threonine. First, we report a diastereoselective synthetic route, which is suitable to produce synthetic material for experimental characterization. The addition of the commercially available ethyl isocyanoacetate to benzyloxyacetaldehyde led to the corresponding benzyloxy-oxazoline, which was hydrolyzed and transformed into ethyl (4S*,5S*)-5-hydroxymethyl-2-oxo-4-oxazolidinecarboxylate in a few steps. Fluorination with diethylamino sulfur trifluoride (DAST) afforded ethyl (4S*,5S*)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate, which was deprotected to give the desired diastereomerically pure 4-fluoro-threonine, in 8–10% overall yield. With the synthetic material in our hands, acid–base titrations have been carried out to determine acid dissociation constants and the isoelectric point, which is the testing ground for the theoretical analysis. We have used machine learning coupled with quantum chemistry at the state-of-the-art to analyze the conformational space of 4-fluoro-threonine, with the aim of gaining insights from the comparison of computational and experimental results. Indeed, we have demonstrated that our approach, which couples a last-generation double-hybrid density functional including empirical dispersion contributions with a model combining explicit first-shell molecules and a polarizable continuum for describing solvent effects, provides results and trends in remarkable agreement with experiments. Finally, the conformational analysis applied to fluoro amino acids represents an interesting study for the effect of fluorine on the stability and population of conformers.

An expedient synthesis of cyanoformates via DAST-mediated C[sbnd]C bond cleavage of α-oximino-β-ketoesters

A new protocol to synthesize cyanoformates was developed using simple β-ketoesters as substrates. (Diethylamino)sulfur trifluoride (DAST) was used as a dual-role reagent to activate the oxime moiety and to donate a fluoride. The key intermediates, α-oximino-β-ketoesters, were prepared by highly efficient acid-assisted oximation of β-ketoesters. Then, the deconstruction of α-oximino-β-ketoesters by the fluorinative CC bond cleavage was demonstrated to provide cyanoformates. In this event, the fluoride addition followed by the CC bond cleavage selectively occurred in the ketones over esters. Due to simple and mild reaction conditions, variously functionalized cyanoformates were exemplified.

Reaction of Dialkylaminosulfur Trifluorides with β‐Keto Sulfonamides and β‐Keto Sulfones

AbstractThe reaction of β‐keto sulfones and β‐keto sulfonamides bearing an unsubstituted α‐methylene unit with (diethylamino)sulfur trifluoride (DAST) and morpholinosulfur trifluoride (morphDAST) led to α‐fluoro‐α‐(dialkylamino)thio‐β‐keto sulfones (sulfonamides). For the β‐keto sulfonamides bearing an α‐methyl substituent, the Cα−Cβ bond cleavage was observed upon reaction with DAST reagents, resulting in formation of (α‐fluoro‐α‐(dialkylamino)thio)ethyl sulfonamides. The structure of the products was confirmed by an X‐ray diffraction study, and mechanistic insights of the process have been presented.

Direct Synthesis of Thiocarbamoyl Fluorides and Trifluoromethylamines Through Fluorinative Desulfurization

Herein, a straightforward synthesis of thiocarbamoyl fluorides is reported starting from amines and carbon disulfide. The key to success is the fluorinative desulfurization of carbon disulfide with (diethylamino)sulfur trifluoride (DAST). The title compounds were obtained in moderate to very good isolated yields. Furthermore, we demonstrated also that thiocarbamoyl fluoride can be converted into their trifluoromethylamine analogues through simple treatment with silver fluoride.

Molecular rearrangements of poststerone derivative steroid core with formation of unique D-homostructures of pregnane and androstane series

20R-Hydroxy short-chain ecdysteroids were synthesized by chemo- and stereoselective reduction of poststerone acetonide with L-Selectride or LiAlH4. The same reaction with the excess of L- Selectride followed by the treatment of the reaction mixture with hydrochloric acid is accompanied by (8R)-13(14 → 8)abeo- rearrangements, which resulted in the contraction/expansion of C/D pregnane rings. The reaction of 20R-hydroxy poststerone analogs with (diethylamino)sulfur trifluoride (DAST) proceeds through intramolecular rearrangements and provides D-homo- or 13,14-seco- androstane structures.

Chaetoglobosins from Chaetomium globosum, an Endophytic Fungus in Ginkgo biloba, and Their Phytotoxic and Cytotoxic Activities

In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, Vb, and C (1-5), in three media. In the present work, five known chaetoglobosins, C, E, F, Fex, and 20-dihydrochaetoglobosin A (5-9), together with the four known compounds (11-14), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (7) with (diethylamino)sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin Fa (10), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds 1, 3-8, and 10 were assayed on radish seedlings; some of these compounds (1, 3, and 6-8) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds 1 and 8-10 showed remarkable cytotoxicity with IC50 values ranging from 3.15 to 8.44 μM, in comparison to the positive drug etoposide (IC50 = 2.13 μM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin Fa (10) displayed a markedly increased cytotoxicity but decreased phytotoxicity.

Studies toward terminal (fluoroalkyl)silanes. Investigation of diethylaminosulfur trifluoride (DAST) in exchange reactions with some terminal (hydroxyalkyl)silanes

Aiming at a convenient way toward the synthesis of terminal (fluoroalkyl)silanes, the effect of (diethylamino)sulfur trifluoride (DAST) on some terminal hydroxyalkylsilanes was investigated. Reaction of DAST with a substituted (hydroxyethyl)diphenylsilane led to the formation of the desired (2-fluoroethyl)diphenylsilane in considerable amounts although the competing elimination route was still the favored mechanism. This new reaction was studied under various parameters with the best conditions yielding the substitution product in a ratio of 1:4 over the undesired elimination product. In a different approach trying to optimize the outcome of the reaction, the presence of two bulky 2,4,6-trimethoxyphenyl (TMOP) groups on the silicon atom favored the elimination route.

The synthesis of a series of deoxygenated 2,3-difluoro-N-acteylneuraminic acid derivatives as potential sialidase inhibitors

Here we describe the successful syntheses of a series of 4-, 7-, 8- and 9-deoxygenated 2,3-difluoro-N-acetylneuraminic acid derivatives as potential mechanism-based inhibitors of sialidases. The syntheses commenced utilising an enzyme-catalysed aldolase reaction between N-acetyl mannosamine and β-fluoropyruvic acid to give 3-fluoro-N-acetyl-neuraminic acid. This common intermediate was then used in selective protection protocols and Barton–McCombie deoxygenations to generate the complete set of mono-deoxygenated 3-fluoro-N-acetylneuraminic acid derivatives. Finally, a fluorination step utilising (diethylamino)sulfur trifluoride (DAST) was used to successfully generate each of the target difluorides.

Morpholine sulfur trifluoride: Vibrational spectra, conformational properties and crystal structure

Analysis of the vibrational spectra and quantum chemical calculations for morpholine sulfur trifluoride, SF3N(CH2CH2)2O, demonstrate that the morpholine ring possesses chair conformation and occupies an equatorial position of the trigonal bipyramidal SF3 group. The compound exists in the gas phase as a mixture of two conformers. The conformer with the SF3 group in equatorial orientation relative to the six-membered morpholine ring is slightly more stable than the axial conformer and the equilibrium is surprisingly temperature independent. MP2 and B3LYP calculations with cc-pVTZ basis sets predict free energy differences ΔG°=G°ax−G°eq of +0.18 and +0.40kcal/mol, respectively. At temperatures below 12°C the title compound crystallizes and the structure of the equatorial conformer, which is the only form present in the crystal, was determined by X-ray diffraction. At 131(1)K a phase transition occurs and the low and high temperature forms were studied at 100 and 150K, respectively.

Fluorinated and rearranged gedunin derivatives

When treated with (diethylamino)sulfur trifluoride (DAST), 11α-hydroxygedunin gave 11β-fluorogedunin and 9,11-didehydrogedunin, whereas deacetylgedunin afforded two skeletal rearranged products 6 and 7, in which the Me-30 had shifted from position 8 to position 7. Of those products, 11β-fluorogedunin and 6 were shown to be more cytotoxic than gedunin on P-388 leukemia cells.

Stereoselective Preparation of 3‐Amino‐2‐fluoro Carboxylic Acid Derivatives, and Their Incorporation in Tetrahydropyrimidin‐4(1H)‐ones, and in Open‐Chain and Cyclic β‐Peptides

AbstractThe preparation of (2S,3S)‐ and (2R,3S)‐2‐fluoro and of (3S)‐2,2‐difluoro‐3‐amino carboxylic acid derivatives, 1–3, from alanine, valine, leucine, threonine, and β3h‐alanine (Schemes 1 and 2, Table) is described. The stereochemical course of (diethylamino)sulfur trifluoride (DAST) reactions with N,N‐dibenzyl‐2‐amino‐3‐hydroxy and 3‐amino‐2‐hydroxy carboxylic acid esters is discussed (Fig. 1). The fluoro‐β‐amino acid residues have been incorporated into pyrimidinones (11–13; Fig. 2) and into cyclic β‐tri‐ and β‐tetrapeptides 17–19 and 21–23 (Scheme 3) with rigid skeletons, so that reliable structural data (bond lengths, bond angles, and Karplus parameters) can be obtained. β‐Hexapeptides Boc[(2S)‐β3hXaa(αF)]6OBn and Boc[β3hXaa(α,αF2)]6‐OBn, 24–26, with the side chains of Ala, Val, and Leu, have been synthesized (Scheme 4), and their CD spectra (Fig. 3) are discussed. Most compounds and many intermediates are fully characterized by IR‐ and 1H‐, 13C‐ and 19F‐NMR spectroscopy, by MS spectrometry, and by elemental analyses, [α]D and melting‐point values.

Synthesis and Anti‐HIV‐1 Activity of New Fluoro‐HEPT Analogues: An Investigation on Fluoro versus Hydroxy Substituents

Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.

ChemInform Abstract: Synthesis of Fluorinated Derivatives of Methionine and 5′-Deoxy-5′-( methylthio)adenosine Using the McCarthy Transformation of Sulfoxides to α-Fluoro Thioethers.

Abstract Treatment of N-acetylmethionine sulfoxide methyl ester with diethylamino- sulfur trifluoride (DAST) or dimethylaminosulfur trifluoride (meDAST) yielded N-acetyl-S-(monofluoromethyl)homocysteine methyl ester as the sole fluorinated product. In contrast, treatment of 2′,3′-di-O-acetyl-5′-(methylthio)adenosine sulfoxide with DAST or meDAST unexpectedly produced three novel fluorinated products.

ChemInform Abstract: A Novel Route for the Synthesis of Deoxy Fluoro Sugars and Nucleosides.

The reaction of (diethylamino)sulfur trifluoride (DAST) with methyl 5-O-benzoyl-β-D-xylofuranoside (1) followed by column chromatography afforded the riboside 2 (62%) and the ribo-epoxide 3 (18%) (Scheme 1). Under similar reaction conditions, the α-D-anomer 4 gave the riboside 5 and the difluoride 6 in 60 and 9% yield, respectively. Treatment of the β-D-xyloside 10 with DAST gave, after chromatographic purification, the riboside 11 as the principal product (48%; Scheme 2). These results suggest that the C(3)−O−SF2NEt2 derivatives were initially formed in the case of the xylosides studied. The distinctive feature of the reaction of DAST with the β-D-arabinoside 12 consists in the formation of a 3- or 5-benzylideneoxoniumyl-substituted intermediate on one of the consecutive transformations, which finally give rise to the inversion of the configuration at C(3) affording the xylosides 17 (18%) and 18 (55%); the lyxoside 14 was also isolated from the reaction mixture in a yield of 25% (Scheme 3). In the presence of the non-participating 5-O-trityl group, i.e., from the reaction products of 21 with DAST, the compounds 23 and 24 were isolated in 16 and 52% yield, respectively (Scheme 4). It may be thus reasonable to conclude that, in the case of the β-D-arabinosides 12 and 21, the principal route of the reaction is the formation of the intermediate C(2)−O−SF2NEt2 derivative. Unlike 21, the α-D-arabinoside 26 was converted to the lyxo-epoxide 25 (53%) and the lyxoside 27 (14%), which implies the intermediate formation of the C(3)−O−SF2NEt2 derivative (Scheme 5).

Efficient regeneration of the 5-acetamido group of a neuraminic acid aryl glycoside from the O-nethyl acetimidate function under acidic conditions

Treatment of protected N-acetylneuraminic acid 2-formyl-4-nitrophenyl glycoside with (diethyl-amino)sulfur trifluoride (DAST) and methanol resulted, apart from the known transformation of the formyl group into a difluoromethyl one, in an undocumented formation of 5-(O-methyl acetimidate) of Neu5Ac. This imidate was converted into the target 5-acetamido derivative under the action of aqueous TFA. The yield of the target product (94%) was twice as high as that reported earlier.