Copper-Mediated Oxidative Chloro- and Bromodifluoromethylation of Phenols.

The first oxidative chloro- and bromodifluoromethylation of phenols with (CH)SiCFX and CuX (X = Cl or Br) in the presence of Selectfluor under mild reaction conditions was developed. This protocol provided a practical and efficient method for the synthesis of a diverse range of biologically valuable and synthetically challenging chloro- and bromodifluoromethyl aryl ethers. Preliminary mechanistic studies suggest that this reaction proceeded through a difluorocarbene-involved oxidative coupling process.

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins.

A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with -trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor-acceptor complex between Hantzsch ester and -trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility.

Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation.

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction.

-Trifluoromethoxyphthalimide: A Shelf-Stable Reagent for Nucleophilic Trifluoromethoxylation.

Due to the unique properties of the OCF group, trifluoromethyl ether compounds play an important role in pharmaceuticals and agrochemicals. Recently, considerable attention has been focused on the development of practical and convenient reagents for the direct incorporation of the OCF group into organic compounds. Herein, we reported a new trifluoromethoxylating reagent -trifluoromethoxyphthalimide (Phth-OCF).

Photoredox-Catalyzed and Silane-Mediated Hydrofluoromethylation of Unactivated Alkenes with Fluoroiodomethane in Water.

The first hydrofluoromethylation of unactivated alkenes with fluoroiodomethane and hydrosilanes is developed by merging photoredox catalysis and silane-mediated deiodination processes. The key to the success of this reaction is the use of water as the solvent to enhance the activity of CHF radical toward unactivated alkenes.

Visible-Light-Induced Nickel-Catalyzed Radical Cross-Couplings to Access α-Aryl-α-trifluoromethyl Alcohols.

A photochemically induced nickel-catalyzed radical cross-coupling of phthalimido trifluoroethanol with aryl bromides to furnish α-aryl-α-trifluoromethyl alcohols is reported. This reaction proceeds via a photoinduced charge transfer of an electron donor-acceptor complex between Hantzsch ester and phthalimido trifluoroethanol, followed by 1,2-hydrogen atom transfer, to generate the α-hydroxytrifluoroethyl radical for the cross-coupling of aryl bromides. No exogenous photocatalysts or stoichiometric metal reductants are required in this mild and operationally simple protocol.

General Synthesis of -Trifluoromethyl Compounds with -Trifluoromethyl Hydroxylamine Reagents.

-CF compounds constitute valuable targets in medicinal chemistry. Extensive studies have been reported for the preparation of -CF compounds through fluorination and trifluoromethylation of N-containing compounds. The development of new synthetic methods from abundant and easily available substrates is highly desirable but still challenging.

Photoredox catalyzed C-H trifluoroethylamination of heteroarenes.

The first C-H trifluoroethylamination of heteroarenes with previously unknown -trifluoroethyl hydroxylamine reagents was achieved under photoredox catalyzed conditions. In the presence of an iridium(III) photoredox catalyst, a variety of heteroarenes, such as indoles, benzofurans, and benzothiophenes, were smoothly converted to the trifluoroethylaminated products in moderate to high yields and with excellent regioselectivity.

Electrochemical Trifluoromethoxylation of (Hetero)aromatics with a Trifluoromethyl Source and Oxygen.

Trifluoromethoxylated aromatics (ArOCF ) are valuable structural motifs in the area of drug discovery due to the enhancement of their desired physicochemical properties upon the introduction of the trifluoromethoxy group (CF O). Although significant progress has been made recently in the introduction of CF O group into aromatics, current methods either require the use of expensive trifluoromethoxylation reagents or require harsh reaction conditions. We present a conceptually new and operationally simple protocol for the direct C-H trifluoromethoxylation of (hetero)aromatics by the combination of the readily available trifluoromethylating reagent and oxygen under electrochemical reaction conditions.

Nucleophilic and Radical Heptafluoroisopropoxylation with Redox-Active Reagents.

The heptafluoroisopropyl group (CF(CF ) ) is prevalent in pharmaceuticals and agrichemicals. However, heptafluoroisopropoxylated (OCF(CF ) ) compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox-active N-OCF(CF ) reagents.

The role of G-protein-coupled receptor kinase 2 in diabetic mechanical hyperalgesia in rats.

Background: Previous studies have indicated a negative correlation between GRK2 expression and pain development and transmission. Here, we investigated whether G-protein-coupled receptor kinase 2 (GRK2) was involved in regulating diabetic mechanical hyperalgesia (DMH).

Methods: The adeno-associated viral vectors containing the GRK2 gene (AAV-GRK2) were used to up-regulate GRK2 protein expression.

Chemoselective Hydro(Chloro)pentafluorosulfanylation of Diazo Compounds with Pentafluorosulfanyl Chloride.

Pentafluorosulfanyl chloride (SF Cl) is the most prevalent reagent for the incorporation of SF group into organic compounds. However, the preparation of SF Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF Cl in n-hexane under gas-reagent-free conditions.

Photoredox-Catalyzed Addition of Dibromofluoromethane to Alkenes: Direct Synthesis of 1-Bromo-1-fluoroalkanes.

Reported herein is a direct and efficient route to 1-bromo-1-fluoroalkanes through the reaction of unactivated alkenes with dibromofluoromethane under photoredox catalysis. The key to the success of these addition reactions is the employment of a suitable photoredox catalyst. In particular, hydro- and bromo-bromofluoromethylated products were chemoselectively formed using THF and DMF/HO as solvents, respectively.

Copper and Zinc Copromoted Bromo(chloro)trifluoromethylation of Alkenes and Alkynes with Trifluoromethanesulfonic Anhydride.

The first copper and zinc copromoted trifluoromethylation using trifluoromethanesulfonic anhydride (TfO) as a trifluoromethylating reagent has been developed. The reaction of alkenes or alkynes with TfO in the presence of CuX (X = Br, Cl), Zn powder, and 2,2'-bipyridine affords bromo(chloro)trifluoromethylated products in good yields. CuX plays a dual role as the catalyst and halide source, whereas 2,2'-bipyridine acts as both the activation reagent and ligand.

Copper-catalyzed chemoselective C-H functionalization of quinoxalin-2(1)-ones with hexafluoroisopropanol.

An unexpected three-component reaction of quinoxalin-2(1H)-ones, tert-butyl peroxybenzoate (TBPB), and hexafluoroisopropanol (HFIP) is described. Under CuBr-catalyzed and TBPB-oxidized conditions, a variety of hydroxyhexafluoroisobutylated quinoxalin-2(1H)-ones were formed. Furthermore, the first hexafluoroisopropoxylation of the quinoxalin-2(1H)-ones with HFIP is also demonstrated with Cu2O as the catalyst and PhI(OAc)2 as the oxidant.

Silver-Catalyzed C-H Aryloxydifluoromethylation and Arylthiodifluoromethylation of Heteroarenes.

The oxidative C-H aryloxydifluoromethylation and arylthiodifluoromethylation of heteroaromatic compounds through the decarboxylation of easily accessible aryloxydifluoroacetic acids and arylthiodifluoroacetic acids, respectively, are disclosed. These reactions are promoted by the combination of catalytic AgNO and Selectfluor or KSO to give ArOCF- and ArSCF-substituted heteroaromatic compounds in moderate to high yields.

Nickel-Mediated Trifluoromethylation of Phenol Derivatives by Aryl C-O Bond Activation.

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes.

Cascade trifluoromethylthiolation and cyclization of -[(3-aryl)propioloyl]indoles.

A cascade oxidative trifluoromethylthiolation and cyclization of -[(3-aryl)propioloyl]indoles with AgSCF is described. This protocol allows for the synthesis of novel bis(trifluoromethylthiolated) or trifluoromethylthiolated pyrrolo[1,2-]indol-3-ones in moderate to good yields. Mechanistic investigations indicated that radical processes were probably involved in these transformations.

Oxidative Hydro-, Bromo-, and Chloroheptafluoroisopropylation of Unactivated Alkenes with Heptafluoroisopropyl Silver.

Oxidant-induced three-component hydro-, bromo-, and chloroheptafluoroisopropylation of unactivated alkenes are disclosed. In these reactions, the CF(CF) radical was generated from the oxidation of AgCF(CF). Then the addition of this perfluorinated radical to alkenes, followed by hydrogenation, bromination, or chlorination, gave the corresponding difunctionalized CF(CF)-containing products in high yields.

Hydrotrifluoromethylthiolation of Unactivated Alkenes and Alkynes with Trifluoromethanesulfonic Anhydride through Deoxygenative Reduction and Photoredox Radical Processes.

An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of trifluoromethanesulfonic anhydride (Tf O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf O in the presence of PMePh and H O under visible-light photoredox catalysis gave the addition products.

Polymicrobial bacteremia after treatment of transcatheter arterial chemoembolization: A case report.

Rationale: Bacteremia caused by polymicrobial infections are rare but dangerous. We report a case of hepatic abscess combined with polymicrobial bacteremia in a 49-year-old male patient after surgery and transcatheter arterial chemoembolization (TACE).

Patient Concerns: The patient was admitted to hospital with metastatic liver cancer for periodic chemotherapy and developed a high fever and tenderness to the liver following surgery and TACE.

Argentination of Fluoroform: Preparation of a Stable AgCF Solution with Diverse Reactivities.

The transformation of a large-volume industrial by-product and stable greenhouse gas fluoroform (HCF ) to useful products has recently received significant attention. Now, a simple and scalable preparation of AgCF by treatment of HCF with t-BuOK and AgOAc is disclosed. The reactivity of the HCF -derived AgCF has been demonstrated by hydrotrifluoromethylation of alkenes and C-H trifluoromethylation of (hetero)arenes.

Genetic polymorphisms of melatonin receptors 1A and 1B may result in disordered lipid metabolism in obese patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a condition in which a woman's levels of the sex hormones (estrogen and progesterone) are out of balance, leading to the growth of ovarian cysts. PCOS can affect the menstrual cycle, fertility, cardiac function and even appearance of women. Therefore, we aimed to explore the genetic polymorphism of the melatonin receptors 1A and 1B in obese patients with PCOS to identify a new theoretical basis for its treatment.

Synthesis of CMeCF-Containing Heteroarenes via Tandem 1,1-Dimethyltrifluoroethylation and Cyclization of Isonitriles.

A tandem 1,1-dimethyltrifluoroethylation and cyclization of isonitriles with 3,3,3-trifluoro-2,2-dimethylpropanoic acid was developed. This protocol provides the efficient synthesis of a series of previously unknown CMeCF-containing heteroarenes, which are potentially useful in the drug discovery process.

Transition metal free decarboxylative fluoroalkylation of N-acrylamides with 3,3,3-trifluoro-2,2-dimethylpropanoic acid (TFDMPA).

A novel transition metal-free decarboxylative fluoroalkylation of activated alkenes and C-H functionalization cascade process has been developed. This approach provides an efficient way to construct valuable 1,1-dimethyl-2,2,2-trifluoroethyl substituted oxindoles.