Direct C7-H Arylation of Pyrazolo[1,5-a]azines with Aryl Chlorides.

C7-Arylated pyrazolo[1,5-a]azines are important structural motifs with profound applications in drug and material research. Here, we report a general and straighforward synthesis of these bi(hetero)aryls via palladium-catalyzed direct C-H arylation, employing low-cost and abundant (hetero)aryl chlorides as the aryl source. The catalytic system is robust and covers a wide substrate scope regarding heteroarenes as well as (hetero)aryl chlorides, with possible extension to the C-H arylation of [1,2,4]triazolo[1,5-a]pyrimidines. This study also presents a rare example of using (hetero)aryl chlorides for the direct C-H arylation of six-membered heteroarenes.

Influence of Achiral Phosphine Ligands on a Synergistic Organo- and Palladium-Catalyzed Asymmetric Allylic Alkylation.

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.

Mechanistic implications of Li-S cell function through modification of organo-sulfur cathode architectures.

Copolymeric organo-sulfur based electrodes provide a unique framework to explore and subsequently improve lithium-sulfur (Li-S) cells. There is a general difference in the way copolymers trap lithium during cell function compared to inorganic carbon-sulfur composites. Using a chain-like polyterpene copolymeric architecture involving the copolymerization of squalene monomer with sulfur (poly(S-r-squalene)), the first evidence for distinguishable differences in the entrapment of lithiated species, when using different copolymeric architectures, is provided. Investigation of poly(S-r-squalene) as an active cathode material via X-ray Absorption Near-Edge Structure (XANES) spectroscopy and high-resolution solid-state Nuclear Magnetic Resonance (NMR) reveal notable differences compared to previously studied poly(S-r-DIB) (proposed to have a less branched architecture) between the lithium environments present during electrochemistry that can be directly linked to the copolymeric structural features. Subtle but pertinent effects based on the copolymeric architecture related to the solid-electrolyte interphase (SEI) formed from the electrolytic components are also uncovered through these techniques. This work offers a comprehensive study on poly(S-r-squalene) and reveals that foundational inverse vulcanisation conditions such as choice of crosslinking monomer can dramatically impact lithium transport and SEI formation for the copolymeric electrode.

Catalytic Synthesis of Trifluoromethyl Cyclopropenes and Oligo-Cyclopropenes.

The synthesis of trifluoromethylated cyclopropenes is often associated with important applications in drug discovery and functional materials. In this report, we describe the use of readily available chiral rhodium(II) catalysts for a highly efficient asymmetric cyclopropenation reaction of fluorinated donor-acceptor diazoalkanes with a broad variety of aliphatic and aromatic alkynes. Further studies highlight the unique reactivity of fluorinated donor-acceptor diazoalkanes in the synthesis of oligo-cyclopropenes. Subsequent C-H functionalization of trifluoromethyl cyclopropenes furnishes densely substituted cyclopropene frameworks and also allows the alternative synthesis of bis-cyclopropenes.

[Dialogue between general practitioner and patient regarding tobacco and alcohol consumption, from the patient's standpoint]. / Dialogue entre médecin généraliste et patient : les consommations de tabac et d'alcool en question, du point de vue du patient.

BACKGROUND: General practitioners (GP) are key players in screening and counselling for smokers and alcohol drinkers exceeding French guidelines for low-risk consumption thresholds. Tackling the subject from the patients' perspective, the authors aim at estimating the proportion of the population having discussed their smoking and alcohol consumption with their GPs, and to pinpoint the factors associated with their having done so. METHODS: The data (n=6346) are derived from nationwide representative phone survey in mainland France conducted by the French public health monitoring center Baromètre de Santé publique France. RESULTS: Among the persons aged 18-75 having consulted a GP over the last 12 months (82.5%), 36.7% stated that smoking had been discussed in consultation while 16.8% had talked about alcohol use. For both substances, being a man, a smoker, an excessive alcohol user and having a chronic illness were not only independently associated with being questioned by one's doctor, but also with more frequent patient initiative. About 87% considered it normal to be asked by their GP about their alcohol intake, this proportion being higher among men and people with high incomes. CONCLUSION: Even though a large portion of the population would deem it normal to discuss smoking and alcohol intake in consultation with a GP, the subjects are rarely broached. Our results underline the need to bolster efforts at systematic screening for substance use by GPs.

Halide Anion Triggered Reactions of Michael Acceptors with Tropylium Ion.

Tropylium bromide undergoes noncatalyzed, regioselective additions to a large variety of Michael acceptors. In this way, acrylic esters are converted into ß-bromo-α-cycloheptatrienylpropionic esters. The reactions are interpreted as nucleophilic attack of bromide ions at the electron-deficient olefins and the approach of the tropylium ion to the incipient carbanion. Quantum chemical calculations were performed to elucidate the analogy to the amine- or phosphine-catalyzed Rauhut-Currier reactions. Subsequent synthetic transformations of the bromo-cycloheptatrienylated adducts are reported.

Elucidation of structures and lithium environments for an organo-sulfur cathode.

Composite organo-sulfur cathodes provide a unique platform for the realization of lithium-sulfur (Li-S) cells. However, difficulties arise in the interpretation of the function of these electrodes in Li-S cells and the role they play in suppressing the so-called 'shuttle effect'. This work focuses on monitoring in detail the structural evolution and lithium environments during charge-discharge cycles in a lithium half-cell of an organo-sulfur cathode, which was synthesised by inverse vulcanisation with 1,3-diisopropenylbenzene. For the first-time in organo-sulfur materials, high resolution solid state 7Li-1H and 13C-1H double resonance NMR spectroscopy coupled with X-ray absorption near-edge structure (XANES) and X-ray diffraction (XRD) are used to develop a detailed structural model of the cathode material and its lithium environments as a function of cycle number. This work provides the first experimental evidence via 2D NMR spectroscopy of distinct molecular proximities of the lithium species with respect to the sulfur, the organic skeleton and the electrolyte in the cathode material. This approach enables us to develop unparalleled understanding of the mechanisms of the high charge capacity of 607 mA h g-1, rationalising initial capacity drop and suppression of capacity fade with cycling. These results also show new possibilities on how to better understand electrode function to further increase the lithium capacities of organo-sulfur cathode materials, which can in turn lead to performance-enhanced Li-S cells.

Efficient Synthesis of α-Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem-Difluoroalkenes.

A facile synthetic procedure for the preparation of α-trifluoromethyl carboxylic acids and esters was achieved through multicomponent coupling reactions between gem-difluoroalkenes, cesium fluoride, and carbon dioxide. The products were generated in moderate to excellent yields, and the synthetic utility of this method was demonstrated through the preparation of trifluoromethylated versions of popular nonsteroidal anti-inflammatory drugs (NSAIDs).

Tropylium-Promoted Oxidative Functionalization of Tetrahydroisoquinolines.

Structural modification of the tetrahydroisoquinoline (THIQ) framework is of significant interest to organic chemists due to its central role in heterocyclic and medicinal chemistry. Here we demonstrate an efficient metal-free method for the oxidative functionalization of THIQs at the C1 position, which is amenable to a diverse range of C-C coupling reactions. These reactions proceed through a hydride abstraction involving the tropylium ion followed by quenching the generated iminium intermediates with nucleophiles to afford THIQ derivatives with excellent efficiencies and interesting selectivities.

NHC-Catalyzed Metathesis and Phosphorylation Reactions of Disulfides: Development and Mechanistic Insights.

The development of efficient methods for the metathesis and phosphorylation reactions of disulfide compounds is of widespread interest due to their important synthetic utility in polymer, biological, medicinal and agricultural chemistry. Herein, we demonstrate the use of N-heterocyclic carbenes (NHCs) as versatile organocatalysts to promote these challenging reactions under mild conditions. This metal- and oxidant-free protocol is operationally simple with very short reaction times. The interplay between the nucleophilicity and basicity of NHCs in these reactions were also elucidated by NMR studies and high-level ab initio calculations.

Corey-Chaykovsky Reactions of Nitro Styrenes Enable cis-Configured Trifluoromethyl Cyclopropanes.

Trifluoromethyl-substituted cyclopropanes are an attractive family of building blocks for the construction of pharmaceutical and agrochemical agents. This work demonstrated the utilization of fluorinated sulfur ylides as versatile reagents for Corey-Chaykovsky cyclopropanation reactions of nitro styrenes. This protocol favored the synthesis of cis-configured trifluoromethyl cyclopropanes for a broad range of substrates with excellent yields and good diastereoselectivities.

Promotion of Organic Reactions by Non-Benzenoid Carbocyclic Aromatic Ions.

The first three primary members of the non-benzenoid carbocyclic aromatic ion family, namely cyclopropenium, cyclopentadienide, and cycloheptatrienium (tropylium) ions, have planar cyclic structures with (4n+2)π electrons in fully conjugated systems. They fulfill Hückel's rule for aromaticity and hence possess extraordinary stability. Since the historic discovery of tropylium bromide in the late 19th Century, these non-benzenoid aromatic ions have attracted a lot of attention because of their unique combination of stability and reactivity. The charge on the aromatic ions makes them more prone to nucleophilic/electrophilic reactions than the neutral benzenoid counterparts. Within the last seven years, there has been a large number of investigations in utilizing aromatic ions to mediate organic reactions. This Review highlights these recent developments and discusses the potential of aromatic ions in promoting synthetically useful organic transformations.

The Resurgence of the Highly Ylidic N-Heterocyclic Olefins as a New Class of Organocatalysts.

In recent decades, N-heterocyclic carbenes have become established as a prevalent family of organocatalysts. N-Heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes, have recently also emerged as efficient promoters for CO2 fixation and polymerization reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry.

Ionic Nature of a Gemini Surfactant at the Air/Water Interface.

The ionic state of an adsorbed gemini surfactant at the air/water interface was investigated using a combination of surface potential and surface tension data. The combined model was developed and successfully described the experimental data. The results verified the existence of three ionic states of the gemini surfactant in the interfacial zone. Furthermore, the model can quantify the adsorbed concentrations of these species. At low concentrations, the fully dissociated state dominates the adsorption. At high concentrations, the fully associated state dominates, accounting for up to 80% of the total adsorption. In the middle range, the adsorption is dominated by the partially associated state, which has a maximum percentage of 80% at a critical micelle concentration of 0.5. The variation in the ionic state is a unique characteristic of gemini surfactants, which can be the underlying mechanism for their advantages over conventional surfactants.

Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes.

The reductive formylation of amines using CO2 and hydrosilanes is an attractive method for incorporating CO2 into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N-heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO2 and Ph2SiH2. A rhodium-based bis(tzNHC) complex (tz=1,2,3-triazol-5-ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.

Simple synthetic receptors for aspirin.

Shallow methylene-bridged cavitands appended with simple H-bond donor/acceptor groups are shown to bind aspirin. The structural features needed in a synthetic receptor for aspirin binding are defined.

Synthesis of isocoumarins through three-component couplings of arynes, terminal alkynes, and carbon dioxide catalyzed by an NHC-copper complex.

A copper-catalyzed multicomponent coupling reaction between in situ generated ortho-arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO2-incorporating reaction was the use of a versatile N-heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three-component reaction.

Minimally invasive resection of heart valve papillary fibroelastoma: two case reports and review of the literature.

BACKGROUND: Cardiac papillary fibroelastomas are rare, accounting for approximately 10% of all cardiac tumors, with 44% of cases located on the aortic valve and only 15% of cases located on the tricuspid valve. However, the optimal management of papillary fibroelastomas remains varied. CASE PRESENTATION: We present two successful instances of treating heart valve papillary fibroelastomas through minimally invasive surgery. These cases involved heart valve papillary fibroelastomas located in two common sites: the aortic valve on the left heart, which was accessed via an upper hemi-sternotomy, and the tricuspid valve on the right heart, which was accessed via beating heart total thoracoscopy. CONCLUSION: The article consistently demonstrates the effectiveness of a minimally invasive surgical approach in managing heart valve papillary fibroelastomas. This study provides further evidence by presenting two cases of heart valve papillary fibroelastomas - one on the aortic valve and the other on the tricuspid valve - that were successfully treated using this approach, resulting in favorable outcomes.

Diagnostic performance of MRI perfusion and spectroscopy for brainstem glioma grading.

OBJECTIVE: This study investigated the roles of dynamic susceptibility contrast (DSC) perfusion and multivoxel magnetic resonance spectroscopy (MRS) in grading brainstem glioma (BSG). PATIENTS AND METHODS: Our retrospective study comprised 12 patients, including 6 with pathology verified low-grade BSGs and 6 with high-grade BSGs. We examined differences in age, relative cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and the metabolite ratios of choline (Cho)/N-acetyl aspartate (NAA) and Cho/creatine (Cr) between these two groups using the Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve analysis was used to establish cutoff values and assess their usefulness in grading BSG. RESULTS: The Cho/NAA metabolite ratio had the strongest preoperative predictive performance for identifying the correct histological grade among BSGs, with an area under the ROC curve (AUC) value of 0.944 (cutoff: 3.88, sensitivity [Se]: 83.3%; specificity [Sp]: 100%), followed by the Cho/Cr ratio (cutoff: 3.08; AUC: 0.917; Se: 83.3%; Sp: 100%), rCBF (cutoff: 3.56, AUC: 0.917; Se: 83.3%; Sp: 100%), rCBV (cutoff: 3.16, AUC: 0.889; Se: 100%; Sp: 66.7%), and age (cutoff: 9.5 years, AUC: 0.889; Se: 100%; Sp: 83.3%). CONCLUSIONS: rCBF and rCBV values comparing solid tumors with the normal brain parenchyma and the metabolite ratios for Cho/NAA and Cho/Cre may serve as useful indices for establishing BSG grading and provide important information when determining treatment planning and prognosis in patients with BSG.

Palladium-catalyzed oxidative C-H/C-H cross-coupling of pyrazolo[1,5-a]azines with five-membered heteroarenes.

The use of Pd(OAc)2 as the catalyst and AgOAc as the oxidant enabled the direct regioselective oxidative C-H/C-H cross-coupling of pyrazolo[1,5-a]pyrimidines or pyrazolo[1,5-a]pyridines with various five-membered heteroarenes without the need of pre-activation and/or directing groups. Successful coupling partners include thiophenes, benzothiophenes, thiazoles, furans, oxazoles, indoles and imidazo[1,2-a]pyridines.