Diethylaminosulfur 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.

N-Fluoroalkylated Morpholinos - a New Class of Nucleoside Analogues.

The first concise and efficient synthesis of some fluorine-containing morpholino nucleosides has been developed. One synthetic strategy was based on the oxidative ring cleavage of the vicinal diol unit of uridine, cytidine adenosine and guanosine derivatives, followed by cyclisation of the dialdehyde intermediates by double reductive amination with fluorinated primary amines to obtain various N-fluoroalkylated morpholinos. Another approach involved cyclisation of the diformyl intermediates with ammonia source, followed by dithiocarbamate formation and desulfurization-fluorination with diethylaminosulfur trifluoride yielding the corresponding morpholine-based nucleoside analogues with a N-CF3 element in their structure.

The synthesis and manipulation of certain Diels–Alder adducts of levoglucosenone and iso-levoglucosenone

Diels–Alder cycloaddition reactions between the biomass-derived platform molecule levoglucosenone (2) and various cyclic dienes such as α-terpinene produced a range of adducts, including compound 28. Manipulation of these adducts then afforded a series of derivatives. So, for example, reductions of the associated carbonyl groups delivered the corresponding alcohols including compound 29 and on reaction of these with diethylaminosulfur trifluoride rearranged fluorination products such as tetracycle 30 were obtained. An analogous suite of compounds was obtained by manipulation of the Diels–Alder adducts derived from reacting the same dienes with iso-levoglucosenone that was itself obtained through simple manipulation of levoglucosenone. Our earlier studies suggest that various of these derivatives could be used in the production, via ring-opening metathesis polymerisation (ROMP), of new bio-based polymers.

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

AbstractThe unprecedented DAST-mediated (DAST = diethylaminosulfur trifluoride) deoxygenative fluorination of benzoyl-, TBDPS-, and Bn-protected 1-(β-d-4-thioarabinofuranosyl)uracil at the sugar portion was examined. Three kinds of nucleoside (Ns) products were formed: target thiolane Ns, ring-contracted thietane Ns, and anhydro Ns products. The reaction pathway was determined by the electronic effect of the protecting groups at the sugar and base moieties. The benzoylated uracil starting material gave the 2,2′-anhydronucleoside (anhydro Ns) as a major product, whereas the silylated and benzylated starting materials furnished the corresponding fluorinated products, in which the ring-contracted thietanes predominantly formed. The desired thiolane Ns could be obtained as major product by the addition of a pyridine derivative as an additive. Upon reacting N 3-benzoylated 1-(β-d-4-thioarabinofuranosyl)uracil with DAST in the presence of 2,4,6-collidine, the target 2′-deoxy-2′-β-fluoro-4′-thiouracil nucleoside could be obtained in 72% isolated yield along with the corresponding thietane Ns (7%) and anhydro Ns (3%) (thiolane Ns/thietane Ns/anhydro Ns = 10.3:1.00:0.43), with recovery of the starting material (12%). In this study, the first stereoselective synthesis of the β-anomer of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabino-pentofuranosyl)cytosine (4′-thioFAC) has been developed.

(Diethylamino)sulfur Trifluoride (DAST) for Fmoc-Amino Acyl Fluoride Synthesis

(Diethylamino)sulfur Trifluoride (DAST) for Fmoc-Amino Acyl Fluoride Synthesis

Syntheses of Clofarabine and Related C2′-β-fluorinated Nucleoside Analogues

A multistep synthesis of 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine (clofarabine) is described from methyl β-D-ribofuranoside. A new improved method for preparation of 1,2-diacetyl D-ribofuranose derivative was developed via acetolysis of tri-O-pivaloylated D-ribofuranoside and plausible mechanism of the reaction was proposed. Synthesis of 3′,5′-di-O-pivaloyl-2,6-dichloropurine β-D-riboside along with isomeric 2′,5′-di-O-pivaloyl nucleoside was carried out by stereoselective glycosylation reaction of 2,6-dichloropurine with peracylated D-ribofuranose followed by regioselective 2´-O-deacetylation of protected β-ribonucleoside with different bases. Mild C2′-β-fluorination of the purine 3′,5′-di-O-pivaloyl ribonucleoside with an excess of diethylaminosulfur trifluoride afforded protected 2,6-dichloropurine 2′-fluoro β-D-arabinoside as the key intermediate. Efficient route to clofarabine was also investigated using anion glycosylation of 2-chloroadenine potassium salt with the 1-α-bromide and potassium tert-butoxide in binary solvent mixture, chromatography for separation of a mixture of anomeric nucleosides (a β/α ratio of 3.0:1) and deacylation of benzoylated 2′-fluoro β-nucleoside. Novel N6-isopentyl clofarabine analogue was synthesized by a direct alkylation of the parent nucleoside

Theoretical study on the mechanism of the benzaldehyde deoxyfluorination by sulfuryl fluoride and tetramethylammonium fluoride

AbstractOrganic fluoride compounds have a potential widely application in pharmaceutical, chemical, and material industries. The deoxyfluorination of C=O bonds is one of important ways to synthesize the organic fluorides. Recently, one efficient aldehyde deoxyfluorination strategy by sulfuryl fluoride (SO2F2) and tetramethylammonium fluoride (TMAF) under mild condition was proposed with low cost and high yield, and SO2F2 was produced by the reaction of 1,1′‐sulfonyldiimidazole (SDI) and KF in formic acid solvent. Herein, a density functional theory (DFT) study was performed to investigate the nature of this reaction including the SO2F2 formation and the aldehyde deoxyfluorination. The calculated results indicate that in the SO2F2 formation, the formic acid plays an important role and participates in the reaction with SDI and KF to transfer proton and convert imidazole cation into imidazole, and in the aldehyde deoxyfluorination by SO2F2 and TMAF, this study points out that there are two C–F coupling steps in this process, and the second one along a SN2 pathway is the rate‐determining step with a free energy barrier of 9.6 kcal/mol. The fluoride anions (F−) come from TMAF as fluorination reagent, which agree well with experimental results. And SO2F2 acts as deoxidization reagent. In comparison with the benzaldehyde deoxyfluorination by diethylaminosulfur trifluoride (DAST), the aldehyde deoxyfluorination strategy by SO2F2 and TMAF owns thermodynamic and kinetic advantages. This theoretical study could provide theoretical insights to design new reagent for the deoxyfluorination of C=O bonds.

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride-Preparation of New Antitumor Ecdysteroid Derivatives.

Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive compounds. Four ecdysteroids, including a new constituent of Cyanotis arachnoidea, were selected as starting materials for DAST-catalyzed transformations. The newly prepared compounds represented combinations of various structural changes DAST was known to catalyze, and a unique cyclopropane ring closure that was found for the first time. Several compounds demonstrated in vitro antitumor properties. A new 17-N-acetylecdysteroid (13) exerted potent antiproliferative activity and no cytotoxicity on drug susceptible and multi-drug resistant mouse T-cell lymphoma cells. Further, compound 13 acted in significant synergism with doxorubicin without detectable direct ABCB1 inhibition. Our results demonstrate that DAST is a versatile tool for diversity-oriented synthesis to expand chemical space towards new bioactive compounds.

DAST-mediated ring-opening of cyclopropyl silyl ethers in nitriles: facile synthesis of allylic amides via a Ritter-type process.

A diethylaminosulfur trifluoride (DAST)-mediated ring-opening reaction of cyclopropyl silyl ethers in nitriles produced allylic amides in moderate to good yields (up to 87%). Time course studies using ReactIR and O-isotopic labeling mechanistic studies suggested that the present reaction occurs via a Ritter-type process, leading to the formation of allylic amides.

Synthesis of 2-Chloro-2′-Deoxyadenosine (Cladribine) and New Purine Modified Analogues

Theefficient two-step synthesis of 2-chloro-2′-deoxyadenosine (cladribine) via the anion glycosylation of purine potassium salt with the glycosyl chloride in binary solvent mixtures is described. A new method for preparation of diprotected 2-chloro-6-fluoropurine 2′-deoxy-β- D-riboside was developed by treatment of the 2,6-dichloropurine precursor with diethylaminosulfur trifluoride (DAST). Novel N6-alkylated cladribine analogue was synthesized by amination of acylated 2,6-dihalogenopurine nucleosides. It was found that a mild hydrolysis reaction of acylated 2-chloro-6-fluoropurine 2′-deoxy-β-D-riboside gave rise to new purine hydroxylated nucleoside.

Rapid Access to Fluorinated Anilides via DAST-Mediated Deoxyfluorination of Arylhydroxylamines.

A new strategy for the synthesis of fluorinated anilides in the absence of metals and oxidants has been developed. This deoxyfluorination of N-arylhydroxylamines with diethylaminosulfur trifluoride (DAST) proceeded smoothly under mild conditions, and the ortho- or para-fluorinated aromatic amine products were prepared in moderate to good yields. Structurally diverse fluorinated anilides, including heterocyclic and pharmaceutically relevant molecules, can be efficiently constructed by this protocol.

Cover Feature: Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds (Eur. J. Org. Chem. 41/2021)

The Cover Feature shows some of the transformations of molecules using diethylaminosulfur trifluoride (DAST). This minireview reveals that DAST does not only act as a fluorinating reagent, which as a result of nucleophilic substitution replaces the hydroxyl group with a fluorine atom but is also a mediator of other processes. It participates in rearrangement and cyclization reactions, resulting in valuable heterocyclic compounds, both fluorinated and non-fluorinated. Thus, it leads to significant building blocks as well as biologically active molecules. The authors would like to thank Gabriela Orczykowska for the graphic project and creation. More information can be found in the Minireview by M. Kaźmierczak and M. Bilska-Markowska.

Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds

AbstractNucleophilic fluorination is one of the fundamental reactions in organic chemistry, as well as a convenient tool for the synthesis of fluorinated building blocks with a potential biological activity. In this minireview, diethylaminosulfur trifluoride (DAST) mediated reactions leading to valuable building blocks and bioactive compounds will be discussed. We focused on results that have been published since 2010. Transformation of β‐amino alcohols, heterocyclic frameworks synthesis, as well as rearrangement reactions have been described in detail.

Diethylaminosulfur Trifluoride: A Novel, Low-Cost, Stable Double Thiolation Reagent for Imidazo[1,2-α]pyridines.

We report a novel, inexpensive double thiolation reagent that sulfurizes a broad range of imidazo[1,2-α]pyridines under mild conditions. Importantly, diethylaminosulfur trifluoride, as a common nucleophilic fluorinating reagent, was utilized as a novel thiolation reagent.

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.

Facile fabrication of F-doped biomass carbon as high-performance anode material for potassium-ion batteries

Heteroatom doping can effectively improve the electrochemical activity of carbon materials. In this paper, three kinds of fluorine-doped biomass carbon are synthesized using industrial hemp core as the precursor and Poly tetra fluoroethylene (PTFE), Diethylaminosulphur trifluoride (DAST) and Hydrofluoric acid (HF) as fluorinating agents, respectively. Among them, the PTFE-treated biomass carbon (PTFE-CHEMP) is wrapped by fluorine-containing nanotubes, which has the most defects, the most F doping amount and the optimum pore size, and is beneficial to the adsorption of K+. When used as the anode of potassium ion batteries (PIBs), the PTFE-CHEMP electrode can provide an average reversible capacity of 369.6 mAh g−1 (200 mA g−1) in 500 cycles. Even at a high current of 2000 mA g−1, it can still provide an excellent rate capability of 229.3 mAh g−1. Kinetic analysis verify that its excellent rate performance comes from the K+ storage mechanism dominated by surface-driven behavior. In addition, the constant current intermittent titration technique (GITT) shows that it still has the storage capacity for K+ at high potentials. This work not only provides a reference for subsequent research on fluorine-doped biomass carbon, but also provides a potential solution for the production of low-cost, high-capacity PIBs anodes.