Tris(pentafluorophenyl)borane and beyond: modern advances in borylation chemistry

As main-group chemistry, in particular boron chemistry, has expanded and developed over the past 20 years, one reagent has risen to prominence as well. Tris(pentafluorophenyl)borane, B(C6F5)3 (commonly known as BCF), has demonstrated extensive applications in a wide variety of reactions, including borylation, hydrogenation, hydrosilylation, frustrated Lewis pair (FLP) chemistry, Lewis acid catalysis, and more. The high Lewis acidity of B(C6F5)3 is derived from the electronic effects of its three C6F5 rings, rendering it a versatile reagent for a great number of reactions. In addition, the steric bulk of these rings also allows it to function as the Lewis acid in a FLP, granting this reagent yet another synthetically useful application. However, as main-group chemistry continues to evolve as a field, new reagents are required that go beyond BCF, increasing not only the range of reactions available but also the breadth of compounds attainable. Great strides have already been made in order to accomplish this task, and this review will highlight modern advances in boron chemistry relating to borylation reactions. Herein, we will show the recent uses of B(C6F5)3 in borylation reactions while also focusing on current advances in novel borane and borocation usage that eclipses that of the stalwart B(C6F5)3

The propargyl rearrangement to functionalised allyl-boron and borocation compounds

A diverse range of Lewis acidic alkyl, vinyl and aryl boranes and borenium compounds that are capable of new carbon–carbon bond formation through selective migratory group transfer have been synthesised. Utilising a series of heteroleptic boranes [PhB(C6F5)2 (1), PhCH2CH2B(C6F5)2 (2), and E-B(C6F5)2(C6F5)C=C(I)R (R=Ph 3 a, nBu 3 b)] and borenium cations [phenylquinolatoborenium cation ([QOBPh][AlCl4], 4)], it has been shown that these boron-based compounds are capable of producing novel allyl- boron and boronium compounds through complex rearrangement reactions with various propargyl esters and carbamates. These reactions yield highly functionalised, synthetically useful boron substituted organic compounds with substantial molecular complexity in a one-pot reaction

Spirometry: A practical lifespan predictor of global health and chronic respiratory and non-respiratory diseases

Objectives. 1. To review and discuss available evidence supporting that spirometry is an overlooked global health marker, that could be used regularly through the lifespan to monitor human health and predict risk of chronic respiratory and other chronic non-communicable diseases (NCDs). 2. To discuss the challenges and opportunities that this proposal faces.Summary of key data. First, spirometry is essential to assess and monitor respiratory health. Second, spirometry adds prognostic value to other well-accepted health markers used in clinical practice, such as blood pressure, body mass index, glucose and blood lipids, by identifying individuals at risk, not only of respiratory diseases, but also of other NCDs, particularly cardiovascular and metabolic disorders. Conclusion. Although we acknowledge that research gaps still exist, we propose that spirometry assessed during childhood, adolescence and early and late adulthood can be a reproducible, non-invasive, safe and affordable global health marker to identify individuals in the general population at risk of respiratory and non-respiratory NCDs. In this context, spirometry may act as the caged canaries that miners used to carry into mines to alert them of dangerous accumulations of gases, thus providing an early warning and save lives

Borane catalyzed selective diazo cross-coupling towards pyrazoles

Decomposition of donor-acceptor diazo compounds leads to the formation of reactive carbene intermediates. These can undergo a wide variety of carbene transfer reactions to yield synthetically useful products. Herein, we report a selective borane catalyzed cyclization reaction from the combination of two different diazo compounds to afford N-substituted pyrazoles. The selective decomposition of the more reactive α-aryl α-diazoester and subsequent reaction with a vinyl diazoacetate produces N-alkylated pyrazoles in a regioselective manner. Catalytic amounts of tris(pentafluorophenyl)borane (10 mol%) were employed to afford the pyrazole products (36 examples) in yields from 59 to 80%. Extensive DFT studies have been undertaken to interpret the mechanism for this reaction which was found to go through two tandem catalytic cycles, both catalyzed by B(C6F5)3

Chiral carbene–borane adducts: precursors for borenium catalysts for asymmetric FLP hydrogenations

The carbene derived from (1R,3S)-camphoric acid was used to prepare the borane adduct with Piers’ borane 7. Subsequent hydride abstraction gave the borenium cation 8. Adducts with 9-BBN and the corresponding (1R,3S)-camphoric acid-derived carbene bearing increasingly sterically demanding N-substituents (R = Me 9, Et 10, i-Pr 11) and the corresponding borenium cations 12–14 were also prepared. These cations were not active as catalysts in hydrogenation, although 9–11 were shown to undergo carbene ring expansion reactions at 50 °C to give species 15–17. The IBOX-carbene precursors 18 and 19 derived from amino alcohols (S)-valinol and (S)-tert-leucinol (R = i-Pr, t-Bu) were used to prepare borane adducts 20–23. Reaction of the carbenes 1,3-dimethylimidazol-2-ylidene (IMe), 1,3-di-iso-propylimidazol-2-ylidene (IPr) 1-benzyl-3-methylimidazol-2-ylidene (IBnMe), 1-methyl-3-phenylimidazol-2-ylidene (IPhMe) and 1-tert-butyl-3-methylimidazol-2-ylidene (ItBuMe) with diisopinocampheylborane (Ipc2BH) gave chiral adducts: (IMe)(Ipc2BH) 24, (IPr)(Ipc2BH) 25, (IBnMe)(Ipc2BH) 26, (IPhMe)(Ipc2BH) 27, and (ItBuMe)(Ipc2BH) 28. Triazolylidene-type adducts including the (10)-phenyl-9-borabicyclo [3.3.2]decane adduct of 1,3,4-triphenyl-1H-1,2,3-triazolium, rac-29 and the 9-BBN derivative of (S)-2-amino-2′-methoxy-1,1′-binaphthalene-1,2,3-triazolium 34a/b were also prepared. In catalytic studies of these systems, while several species were competent catalysts for imine reduction, in general, low enantioselectivities, ranging from 1–20% ee, were obtained. The implications for chiral borenium cation catalyst design are considered

Divergent elementoboration: 1,3-haloboration versus 1,1-carboboration of propargyl esters

This work showcases the 1,3‐haloboration reaction of alkynes in which boron and chlorine add to propargyl systems in a proposed sequential oxazoliumborate formation with subsequent ring‐opening and chloride migration. In addition, the functionalization of these propargyl esters with dimethyl groups in the propargylic position leads to stark differences in reactivity whereby a formal 1,1‐carboboration prevails to give the 2,2‐dichloro‐3,4‐dihydrodioxaborinine products as an intramolecular chelate. Density functional theory calculations are used to rationalize the distinct carboboration and haloboration pathways. Significantly, this method represents a metal‐free route to highly functionalized compounds in a single step to give structurally complex products

Contrasting frustrated Lewis pair reactivity with selenium- and boron-based Lewis acids

The activation of π‐bonds in diynyl esters has been investigated by using soft and hard Lewis acids. In the case of the soft selenium Lewis acid PhSeCl, sequential activation of the alkyne bonds leads initially to an isocoumarin (1 equiv PhSeCl) and then to a tetracyclic conjugated structure with the isocoumarin subunit fused to a benzoselenopyran (3 equiv PhSeCl). Conversely, the reaction with the hard Lewis acidic borane B(C6F5)3 initiates a cascade reaction to yield a complex π‐conjugated system containing phthalide and indene subunits

Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles

Background: Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective: We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods: Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results: Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion: Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.Peer reviewe

Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice

Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies

Development and evaluation of a cultural competency training curriculum

BACKGROUND: Increasing the cultural competence of physicians and other health care providers has been suggested as one mechanism for reducing health disparities by improving the quality of care across racial/ethnic groups. While cultural competency training for physicians is increasingly promoted, relatively few studies evaluating the impact of training have been published. METHODS: We recruited 53 primary care physicians at 4 diverse practice sites and enrolled 429 of their patients with diabetes and/or hypertension. Patients completed a baseline survey which included a measure of physician culturally competent behaviors. Cultural competency training was then provided to physicians at 2 of the sites. At all 4 sites, physicians received feedback in the form of their aggregated cultural competency scores compared to the aggregated scores from other physicians in the practice. The primary outcome at 6 months was change in the Patient-Reported Physician Cultural Competence (PRPCC) score; secondary outcomes were changes in patient trust, satisfaction, weight, systolic blood pressure, and glycosylated hemoglobin. Multiple analysis of variance was used to control for differences patient characteristics and baseline levels of the outcome measure between groups. RESULTS: Patients had a mean of 2.8 + 2.2 visits to the study physician during the study period. Changes in all outcomes were similar in the "Training + Feedback" group compared to the "Feedback Only" group (PRPCC: 3.7 vs.1.8; trust: -0.7 vs. -0.2 ; satisfaction: 1.9 vs. 2.5; weight: -2.5 lbs vs. -0.7 lbs; systolic blood pressure: 1.7 mm Hg vs. 0.1 mm Hg; glycosylated hemoglobin 0.02% vs. 0.07%; p = NS for all). CONCLUSION: The lack of measurable impact of physician training on patient-reported and disease-specific outcomes in the current has several possible explanations, including the relatively limited nature of the intervention. We hope that the current study will help provide a basis for future studies, using more intensive interventions with different provider groups