Vinylogous Michael cascade reactions employing silyl glyoxylates and silyl glyoximides

I. Vinylation-Initiated Vinylogous Michael Cascade of Silyl Glyoxylates and Elaboration to Nitrocyclopentanols: An investigation of the reaction parameters required to achieve a vinylation-initiated vinylogous Michael cascade of silyl glyoxylates and nitroalkenes was performed. The reaction achieved the (Z)-enol silane products with complete regio- and diastereoselectivity. A rationale for the high levels of selectivity is discussed. Discussion of how the probable mechanism of the three-component coupling was discerned (vinylogous Michael, [3,3] rearrangement, or Diels-Alder type pathway) is presented. This method provides an easily accessible synthetic equivalent to the unusual a-keto ester homoenolate. These (Z)-enol silane products were further elaborated to nitrocyclopentanols via a highly diastereoselective Henry cyclization. Rationale for the diastereoselectivity is presented as well as an analysis of this methodology's impact compared to other methods for highly substituted nitrocyclopentanols is also presented. II. Alkynylation-Initiated Vinylogous Michael Reaction of Silyl Glyoxylates and Elaboration to Cyclopentanol Derivatives: An investigation of the reaction parameters necessary to accomplish an alkynylation-initiated Kuwajima-Reich/vinylogous Michael cascade of silyl glyoxylates and nitroalkenes is presented. The title three-component coupling provided tetrasubstituted silyloxyallenes with high levels of regio- and diastereoselectivity. The impressive selectivity of this transformation was investigated through a quantum mechanical study using the density functional theory approach at the level of B3LYP/6-311G(d). This study corroborated previous studies on the identity of the transient secondary nucleophile as the (Z)-glycolate enolate and provided a rationale for the excellent diastereoselectivity observed through nitro group coordination to the (Z)-glycolate enolate. A discussion of the additional empirical studies performed to confirm the proposed mechanism is also presented. The tetrasubstituted silyloxyallene products were then derivatized to cyclopentenols and cyclopentitols. III. Silyl Glyoximides as Asymmetric Conjunctive Reagents Through Long-Range Stereoinduction: The utility of silyl glyoximides as a new class of asymmetric conjunctive reagents in the vinylation-initiated vinylogous Michael cascade with vinyl Grignard and nitroalkenes is presented. The reaction affords the desired gamma-adducts with excellent regio-and diastereoselectivity. A rationale for this long range stereochemical transmission is proposed. A discussion of the benefits of silyl glyoximides compared to silyl glyoxylates in terms of the current methodology is presented. Initial studies towards the various Henry cyclizations are also presented

On the importance of fiber curvature to the elastic moduli of electrospun nonwoven fiber meshes

Adequate mechanical integrity of nonwoven fabrics is generally a prerequisite for their practical usage. Nonwoven fiber mats of poly(trimethyl hexamethylene terephthalamide) (PA 6(3)T) with average fiber diameters from 0.1 to 3.6 microns were electrospun from solutions in dimethylformamide and formic acid and their in-plane mechanical response characterized. Two quantitative microstructure-based models that relate the Young’s moduli of these fabrics to those of the fibers are considered, one assuming straight fibers and the other allowing for curved fibers. It is found that the model allowing for curved fibers provides a quantitative relationship between the Young’s moduli of the mats and those of the fibers themselves. The governing factors that affect the mechanical properties of nonwoven mats are the porosity of the mats, the intrinsic fiber modulus, and the average fiber diameter, curvature (or “curl”) and distance between fiber-to-fiber junctions. Especially for submicron diameter fibers, both the intrinsic fiber properties and fiber curvature make important contributions to the mechanical behavior of their nonwoven fabrics.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract ARO W911NF-07-D-0004

Updated estimated incidence and prevalence of serious fungal infections in Trinidad and Tobago

Objective: : To estimate the incidence and prevalence of serious fungal infections in Trinidad and Tobago (T&T), with a population of 1 394 973 million. Methods: : The medical literature was searched to obtain published data on the incidence and prevalence of fungal infections in the Caribbean. If data were unavailable, estimations were performed using the frequencies of fungal infection in populations at risk. Asthma and pulmonary tuberculosis rates were used to derive the prevalence of allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitization (SAFS), and chronic pulmonary aspergillosis (CPA). Results: : The estimated annual burden of fungal infections was 46 156 persons (3.3% of the population), including 21 455 women with recurrent vulvovaginal candidiasis, 118 persons with invasive aspergillosis, 3637 adults with ABPA, 4800 with SAFS, and 178 with CPA. Annually, we estimated 70 cases of candidemia and 14 647 cases of tinea capitis in children. Of the 11 000 persons living with HIV/AIDS, it was estimated that there were 40 cases of cryptococcal meningitis, 88 cases of disseminated histoplasmosis, and 124 cases of Pneumocystis pneumonia. Conclusion: : There seems to be an extensive burden of fungal infections in T&T. Hence, targeted interventions are required to improve clinical and laboratory diagnosis and a national surveillance system should be implemented.S

Arylboronic acid-catalyzed racemization of secondary and tertiary alcohols

Funding: Florida Gulf Coast University; University of St Andrews; UK Engineering and Physical Sciences Research Council - EP/J018139/1, EP/L016419/1, EP/V051423/1; Leverhulme Trust - ECF-2014-005.The use of 2-carboxyphenylboronic acid (5 mol %) and oxalic acid (10 mol %) with 2-butanone as a solvent for the racemization of a range of enantiomerically pure secondary and tertiary alcohols is demonstrated. The process is postulated to proceed via reversible Brønsted acid-catalyzed C–O bond cleavage through an achiral carbocation intermediate.Publisher PDFPeer reviewe

Managing anxiety disorders in adults

The GP has a key role in identifying patients presenting with anxiety symptoms and ensuring appropriate acute and long-term management. There are two key messages for GPs to follow: once you have made a diagnosis of an anxiety disorder, tell the patient you have a treatment for it. Second, do not let your anxiety lead you to prescribe inappropriately or overinvestigate for all possible differential diagnoses

Flagellum Pumping Efficacy in Shear-Thinning Viscoelastic Fluids

Microorganism motility often takes place within complex, viscoelastic fluid environments, e.g., sperm in cervicovaginal mucus and bacteria in biofilms. In such complex fluids, strains and stresses generated by the microorganism are stored and relax across a spectrum of length and time scales and the complex fluid can be driven out of its linear response regime. Phenomena not possible in viscous media thereby arise from feedback between the "swimmer" and the complex fluid, making swimming efficiency co-dependent on the propulsion mechanism and fluid properties. Here we parameterize a flagellar motor and filament properties together with elastic relaxation and nonlinear shear-thinning properties of the fluid in a computational immersed boundary model. We then explore swimming efficiency over this parameter space. One exemplary insight is that motor efficiency (measured by the volumetric flow rate) can be boosted vs.\ degraded by moderate vs.\ strong shear-thinning of the viscoelastic environment.Comment: 15 pages, 8 figure

Silicon-Based Solid-State Batteries: Electrochemistry and Mechanics to Guide Design and Operation

Solid-state batteries (SSBs) are promising alternatives to the incumbent lithium-ion technology; however, they face a unique set of challenges that must be overcome to enable their widespread adoption. These challenges include solid-solid interfaces that are highly resistive, with slow kinetics, and a tendency to form interfacial voids causing diminished cycle life due to fracture and delamination. This modeling study probes the evolution of stresses at the solid electrolyte (SE) solid-solid interfaces, by linking the chemical and mechanical material properties to their electrochemical response, which can be used as a guide to optimize the design and manufacture of silicon (Si) based SSBs. A thin-film solid-state battery consisting of an amorphous Si negative electrode (NE) is studied, which exerts compressive stress on the SE, caused by the lithiation-induced expansion of the Si. By using a 2D chemo-mechanical model, continuum scale simulations are used to probe the effect of applied pressure and C-rate on the stress-strain response of the cell and their impacts on the overall cell capacity. A complex concentration gradient is generated within the Si electrode due to slow diffusion of Li through Si, which leads to localized strains. To reduce the interfacial stress and strain at 100% SOC, operation at moderate C-rates with low applied pressure is desirable. Alternatively, the mechanical properties of the SE could be tailored to optimize cell performance. To reduce Si stress, a SE with a moderate Young's modulus similar to that of lithium phosphorous oxynitride (∼77 GPa) with a low yield strength comparable to sulfides (∼0.67 GPa) should be selected. However, if the reduction in SE stress is of greater concern, then a compliant Young's modulus (∼29 GPa) with a moderate yield strength (1-3 GPa) should be targeted. This study emphasizes the need for SE material selection and the consideration of other cell components in order to optimize the performance of thin film solid-state batteries

Construction of Cyclopentanol Derivatives via Three-Component Coupling of Silyl Glyoxylates, Acetylides, and Nitroalkenes

The three-component coupling of Mg acetylides, silyl glyoxylates, and nitroalkenes results in a highly diastereoselective Kuwajima-Reich/vinylogous Michael cascade that provides tetrasubstituted silyloxyallene products. The regio- and diastereoselectivity were studied using DFT calculations. These silyloxyallenes were converted to cyclopentenols and cyclopentitols via a unique Lewis acid assisted Henry cyclization. The alkene functionality present in the cyclopentanol products can be elaborated using diastereoselective ketohydroxylation reactions