Silver-catalyzed formal insertion of arynes into Rf-I bonds.

An unprecedented silver-catalyzed formal insertion of arynes into Rf-I (Rf = CF3, C2F5) bonds has been developed. This protocol provides easy access to various ortho-perfluoroalkyl iodoarenes under mild conditions. In this insertion reaction, an ionic atom-transfer reaction of RfI occurs, and a silver-mediated metathesis process is involved in the efficient transfer of the electropositive iodine atom.

Nucleophilic difluoromethylation of epoxides with PhSO(NTBS)CF₂H by a preorganization strategy.

Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF2H (2; TBS=tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF3⋅Et2O was found to be crucial for the reaction.

On the status of β-cell dysfunction and insulin resistance of breast cancer patient without history of diabetes after systemic treatment.

To estimate the status of β-cell dysfunction and insulin resistance of breast cancer (BC) patient without history of diabetes mellitus (DM) after systemic treatment through an oral glucose tolerance test (OGTT) and insulin releasing test (IRT). All the 128 BC patients without history of DM after systemic treatment underwent OGTT and IRT test. Fasting and 2-h glucose levels were measured to confirm undiagnosed DM and prediabetes.

Copper-mediated trifluoromethylthiolation of α-diazoesters.

A novel Cu-mediated trifluoromethylthiolation of diazo compounds has been developed that provides a convenient synthetic route for the efficient α-trifluoromethylthiolation of simple esters under mild reaction conditions. The reaction is typically carried out at room temperature, and water could be used to promote the reaction.

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine.

Background: 1,1-Difluoroalkenes cannot only be used as valuable precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods.

Results: The combination of (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl) and triphenylphosphine (PPh3) can be used for the synthesis of gem-difluoroolefins from carbonyl compounds.

Rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolomics approach to study the effects of jieduquyuziyin prescription on systemic lupus erythematosus.

Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) prescription, has been widely used for the clinical treatment of systemic lupus erythematosus (SLE). However, the complex chemical constituents of JP and the multifactorial pathogenesis of SLE make research on the therapeutic mechanism of JP in SLE challenging. In this paper, a serum metabolomics approach based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was employed to acquire the metabolic characteristics of serum samples obtained from mice in the SLE model group, JP-treated group, prednisone acetate (PA)-treated group and control group.

[Study on intervention effect of Jieduquyuziyin prescription systemic lupus erythematosus by HPLC-Q-TOF/MS].

To establish a metabonomic method based on high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS), in order to study the changes in serum metabolites of systemic lupus erythematosus (SLE) mice after treatment of Jieduquyuziyin prescription, the pathogenesis of SLE and mechanism of drug action. The orthogonal partial least squares (OPLS) was applied for the pattern recognition of experimental data, finding a significant difference in the control group, the SLE model group, the Jieduquyuziyin prescription-treated group and the prednisone acetate-treated group. According to the OPLS load diagram, 12 differential metabolites, including traumatic acid, PAF, 12 (S)-HEPE, 15(S)-HETrE and Hepoxilin B3 were identified by using accurate mass combined with MS/MS data After treatment with Jieduquyuziyin prescription, the relative contents of PAF, 12 (S)-HETE were close to the level of the control group.

[Extraction, purification and identification of type II collagen from Agkistrodon acutus].

The object of the research was to extract, purify and identify the type II collagen of Agkistrodon acutus. Type II collagen of A. acutus was extracted by enzyme decomposition method, and purified by ion exchange column chromatography.

Divergent rearrangements of cyclopropyl-substituted fluoroepoxides involving C-F bond cleavage and formation.

Unprecedented divergent rearrangements of cyclopropyl-substituted fluoroepoxides are reported. In the presence of a catalytic amount of benzoic acid, cyclopropyl-substituted fluoroepoxides efficiently undergo 1,5-fluorine migration. However, when the fluoroepoxides are heated with K2CO3 at 60 °C, 1,2-fluorine migration occurs.

Stereoselective nucleophilic fluoromethylation of aryl ketones: dynamic kinetic resolution of chiral α-fluoro carbanions.

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state.

AgF-mediated fluorinative homocoupling of gem-difluoroalkenes.

A novel silver(I)-fluoride-mediated homocoupling reaction of β,β-difluorostyrene derivatives is described. The transformation is initiated via nucleophilic addition of silver(I) fluoride to β,β-difluorostyrenes, which is followed by dimerization of the corresponding benzylsilver intermediates. The reaction shows good substrate scope, functional group tolerance, and represents the first report on the reactivity of (α-trifluoromethyl)benzylsilver species.

Copper-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3 via C-F bond cleavage.

A novel Cu-catalyzed gem-difluoroolefination of diazo compounds is described. This transformation starts from readily available TMSCF3 and diazo compounds, via trifluoromethylation followed by C-F bond cleavage, to afford the desired 1,1-difluoroalkene products.

Synthesis of gem-difluorocyclopropa(e)nes and O-, S-, N-, and P-difluoromethylated compounds with TMSCF(2)Br.

Two-in-one: Me3 SiCF2 Br is an efficient difluorocarbene source and is compatible with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1] cycloaddition with alkenes/alkynes and hydroxide ion promoted α-addition with (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine oxides give the corresponding gem-difluorinated compounds with broad functional-group tolerance.

Silver-mediated trifluoromethylation-iodination of arynes.

An unprecedented silver-mediated vicinal trifluoromethylation-iodination of arynes that quickly introduces CF(3) and I groups onto aromatic rings in a single step to give o-trifluoromethyl iodoarenes has been developed. A new reactivity of AgCF(3) has been revealed, and 2,2,6,6-tetramethylpiperidine plays an important role in this difunctionalization reaction.

Copper-mediated fluoroalkylation of aryl iodides enables facile access to diverse fluorinated compounds: the important role of the (2-pyridyl)sulfonyl group.

The (2-pyridyl)sulfonyl group was found to be a multifunctional group in the preparation of structurally diverse fluorinated products. It not only facilitates the copper-mediated (or catalyzed) cross-coupling reaction between α-fluoro sulfone 4a and aryl iodides, but also enables further transformations of the coupling products 2.

Tuning the reactivity of difluoromethyl sulfoximines from electrophilic to nucleophilic: stereoselective nucleophilic difluoromethylation of aryl ketones.

A stereoselective synthesis of enantiomerically enriched difluoromethyl tertiary alcohols by tuning the reactivity of difluoromethyl sulfoximines from electrophilic to nucleophilic difluoromethylating agents is reported. The key feature of this chemistry is the diastereoselective addition of the difluoromethyl sulfoximine to the prochiral carbon of the ketone. The present method was used to prepare enantiomerically enriched difluoromethyl secondary alcohols and difluorinated analogues of the natural products gossonorol and boivinian B, demonstrating the potency of the method.

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3: the important role of water as a promoter.

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF(3) reagent has been developed as a new method to prepare α-trifluoromethyl esters. This trifluoromethylation reaction represents the first example of fluoroalkylation of a non-fluorinated carbene precursor. Water plays an important role in promoting the reaction by activating the "CuCF(3)" species prepared from CuI/TMSCF(3)/CsF (1.

Enantioselective synthesis of cyclopropanes that contain fluorinated tertiary stereogenic carbon centers: a chiral α-fluoro carbanion strategy.

Chiral transfer: the fluorinated sulfoximine (see scheme; Ts=p-toluenesulfonyl) was synthesized and used as the first chiral fluoromethylenation reagent for the synthesis of cyclopropanes that contain fluorinated tertiary stereogenic carbon centers in good yields, good diastereoselectivity, and excellent enantioselectivity.

From olefination to alkylation: in-situ halogenation of Julia-Kocienski intermediates leading to formal nucleophilic iodo- and bromodifluoromethylation of carbonyl compounds.

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of -CF(2)I and -CF(2)Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF(2)Br(-) and CF(2)I(-) to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds.

Copper-catalyzed di- and trifluoromethylation of α,β-unsaturated carboxylic acids: a protocol for vinylic fluoroalkylations.

Dual action: the Lewis acid CuF(2) ⋅2 H(2)O efficiently catalyzes the reaction between electrophilic fluoroalkylating agents and α,β-unsaturated carboxylic acids by dually activating both reactants, thus affording di- and trifluoromethyl alkenes in high yields with excellent E/Z selectivity.

Reactions of sulfur- and phosphorus-substituted fluoroalkylating silicon reagents with imines and enamines under acidic conditions.

Nucleophilic fluoroalkylation reactions of imines and enamines with α-phenylthio, α-phenylsulfonyl, and α-diethylphosphoryl substituted fluorinated silanes have been investigated. The reactions are promoted by hydrofluoric acid generated in situ from potassium hydrodifluoride and trifluoroacetic acid. Sulfur reagents worked well with both imines and enamines, whereas phosphorus reagent efficiently coupled only with enamines.

Efficient and direct nucleophilic difluoromethylation of carbonyl compounds and imines with Me3SiCF2H at ambient or low temperature.

Since 1995, Me(3)SiCF(2)H has been widely believed to be an inefficient difluoromethylating agent, which requires harsh reaction conditions to cleave its rather inert Si-CF(2)H bond. However, it has now been found that, by using a proper Lewis base activator, Me(3)SiCF(2)H can efficiently difluoromethylate various aldehydes, ketones, and imines to give the corresponding products in good to excellent yields at room temperature or even at -78 °C.

Selective fluoroalkylation of organic compounds by tackling the "negative fluorine effect".

The presence of fluorine on a carbanion center will dramatically influence the nucleophilic alkylation reactions. Based on our own experience, we noticed that the fluorine substitution on the carbanionic carbon poses a negative effect in many nucleophilic fluoroalkylation reactions [we propose this effect as "negative fluorine effect (NFE)"]. Two factors were believed to contribute to the NFE: (1) thermal instability of fluorinated carbanions caused by α-elimination (self-decomposition) and (2) the intrinsic nucleophilicity of fluorinated carbanion influenced by the fluorine atoms (such as hard/soft nature of the fluorinated carbanions).