Trifluoromethyl sulfoxides are a new class of trifluoromethylthiolating reagent. The sulfoxides engage in metal‐free C−H trifluoromethylthiolation with a range of (hetero)arenes. The method is also ...applicable to the functionalization of important compound classes, such as ligand derivatives and polyaromatics, and in the late‐stage trifluoromethylthiolation of medicines and agrochemicals. The isolation and characterization of a sulfonium salt intermediate supports an interrupted Pummerer reaction mechanism.
May I interrupt? Taking advantage of the interrupted Pummerer reaction, trifluoromethyl sulfoxides engage in the metal‐free C−H trifluoromethylthiolation of (hetero)arenes, including drug molecules and natural products. This new class of trifluoromethylthiolating reagent exploits a new strategy for trifluoromethylthiolation in which sulfonium salts are assembled and selectively deconstructed.
Sulfonamides are present in a range of useful molecules, such as drugs and agrochemicals. In recent years, the functionalization of sulfonamides via S–N bond cleavage has received increased ...attention. In this report, we detail an accessible and low-cost route for transforming primary sulfonamides into the corresponding sulfonic acids/sulfonates via sulfonyl pyrroles. The reaction is demonstrated with a range of substrates including aryl and alkyl sulfonamides, and in the late-stage functionalization of several sulfonamide-containing drug molecules.
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C2 and C3 substituted benzothiophenes are common structures in medicinal and materials chemistry. The cross-coupling of phenols with benzothiophenes is a useful route towards these important ...molecules. In this report we reveal an efficient C–H/C–H-type cross-coupling of benzothiophenes, activated as their S-oxides, with phenols to give C2/C3 arylated benzothiophenes. Whereas previous reports describe cross-coupling at the ortho-position between phenols and sulfoxides, this procedure allows para-functionalization of phenols that typically have their ortho positions blocked.
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Due to their ubiquity in nature and frequent use in organic electronic materials, benzothiophenes are highly sought after. Here we set out an unprecedented procedure for the formation of ...benzothiophenes by the twofold vicinal C−H functionalization of arenes that does not require metal catalysis. This one‐pot annulation proceeds through an interrupted Pummerer reaction/3,3‐sigmatropic rearrangement/cyclization sequence to deliver various benzothiophene products. The procedure is particularly effective for the rapid synthesis of benzothiophenes from non‐prefunctionalized polyaromatic hydrocarbons (PAHs).
Thio‐Fusion: Benzothiophene werden aus unfunktionalisierten Arenen in einer Sequenz aus unterbrochener Pummerer‐Reaktion, 3,3‐sigmatroper Umlagerung und Cyclisierung erhalten. Der Prozess benötigt keine Metalle, verläuft über eine doppelte C‐H‐Funktionalisierung und kann genutzt werden, um eine einfache π‐Verlängerung von polyaromatischen Kohlenwasserstoffen zu erreichen.
An efficient, enantio‐ and diastereoselective, copper‐catalyzed coupling of imines, 1,3‐enynes, and diborons is reported. The process shows broad substrate scope and delivers complex, chiral ...homopropargyl amines; useful building blocks on the way to biologically‐relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.
Aus Drei mach Eins: Die entio‐ und diastereoselektive Kupfer‐katalysierte Dreikomponenten‐Kupplung von Iminen, 1,3‐Eninen und Diborverbindungen liefert komplexe, chirale Homopropargylamine, nützliche Bausteine für biologisch und medizinisch relevante Verbindungen. Funktionalisierte Homopropargylamine mit bis zu drei benachbarten Stereozentren können in einem einzigen Schritt synthetisiert werden.
Objectives. To investigate the expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) in the synovium of human RA patients as well as the level of soluble TREM-1 in the ...plasma of RA patients. Methods. Twenty-four RA synovial samples were analysed by gene expression oligonucleotide microarrays. Expression levels of TREM-1 mRNA in murine CIA paws were determined by quantitative PCR (qPCR). TREM-1 protein expression was detected by immunohistochemistry in five RA synovial samples and two OA synovial samples. TREM-1-positive cells from five RA synovial tissues were analysed by FACS staining to determine the cell type. Activation of TREM-1 was tested in five RA synovial samples. Soluble TREM-1 was measured in serum from 32 RA patients. Results. The expression of TREM-1 mRNA was found to increase 6.5-fold in RA synovial samples, whereas it was increased 132-fold in CIA paws. Increased numbers of TREM-1-positive cells were seen in RA synovium sections and these cells co-expressed CD14. Using a TREM-1-activating cross-linking antibody in RA synovial cultures, multiple pro-inflammatory cytokines were induced. The average amount of soluble TREM-1 in plasma from RA patients was found to be higher than that in plasma from healthy volunteers. Conclusions. These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.
Copper‐catalyzed borylative multicomponent reactions (MCRs) involving olefins and C−N electrophiles are a powerful tool to rapidly build up molecular complexity. The products from these reactions ...contain multiple functionalities, such as amino, cyano and boronate groups, that are ubiquitous in medicinal and process chemistry programs. Copper‐catalyzed MCRs are particularly attractive because they use a relatively abundant and non‐toxic catalyst to selectively deliver high‐value products from simple feedstocks such as olefins. In this Minireview, we explore this rapidly emerging field and survey the borylative union of allenes, dienes, styrenes and other olefins, with imines, nitriles and related C−N electrophiles.
Copper‐catalyzed borylative multicomponent couplings, involving olefins and C−N electrophiles, constitute an efficient approach to high‐value amine and nitrile products. This Minireview assesses the progress in this rapidly emerging field and surveys the borylative union of allenes, dienes, styrenes, and related olefins, with imines, nitriles, and related electrophiles.
Previous research in humans suggests a relationship between drug abuse and impulsivity as shown by selection of a smaller immediate reward over a larger delayed reward. However, it is not clear ...whether impulsivity precedes drug abuse or drug abuse influences impulsivity.
The hypothesis of the present experiment was that rats selected for choosing smaller, immediate over larger, delayed food would acquire IV cocaine self-administration faster than those choosing larger, delayed food rewards.
Female rats were screened for locomotor activity and trained on a delay discounting procedure that allowed them access to two response levers and a food pellet dispenser. Under a fixed-ratio (FR) 1 schedule, responding on one lever resulted in immediate delivery of one 45 mg pellet, while responding on the other lever resulted in delivery of three 45 mg pellets after a variable delay that increased after responses on the delay lever and decreased after responses on the immediate lever. For each rat, a mean adjusted delay (MAD) was calculated for each daily session, and stability was defined as MADs varying less than 5 s across 5 days. Based on their average MADs, rats were separated into low impulsive (LoI) and high impulsive (HiI) groups, implanted with an indwelling IV catheter, and trained to lever press for cocaine (0.2 mg/kg) under an FR1 schedule.
There were no differences in locomotor activity between the LoI and HiI groups; however, a greater percentage of the HiI group acquired cocaine self-administration, and they did so at a significantly faster rate than the LoI rats.
Performance on the delay discounting model of impulsivity predicted vulnerability to subsequent acquisition of cocaine self-administration.
Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper‐catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone ...motifs. The reaction proceeds with high enantio‐ and diastereocontrol, and can deliver products containing quaternary stereocenters. The utility of the products is demonstrated through further manipulations.
The quinazolinone motif is an important feature in natural products and drug candidates although enantioselective approaches to such scaffolds remain rare. An enantioselective Cu‐catalyzed borylative cyclization delivers pyrroloquinazolines, featuring quaternary stereocenters and synthetic handles for further derivatization, with high enantio‐ and diastereocontrol.
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