Development of a syn‐Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines

Direct coupling of enolizable aldehydes with C‐alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti‐isomers. The combination of proline and a urea Brønsted base cocatalyst is key for the reactions to proceed under very mild conditions (3–10 mol % catalyst loading, dichloromethane as solvent, ?20 °C, 1.2 molar equivalents of aldehyde) and with virtually total stereocontrol (syn/anti ratio up to 99:1; ee up to 99 %). Some possibilities of further chemical elaboration of adducts are also briefly illustrated.     

Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes

An effective asymmetric route to functionalized 1,6‐ and 1,7‐enynes has been developed based on a direct cross‐aldol reaction between ω‐unsaturated aldehydes and propargylic aldehydes (α,β‐ynals) promoted by combined α,α‐dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio‐ and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β‐ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson–Khand conditions.     

Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain

Fluorescence-guided surgery (FGS) is routinely utilized in clinical centers around the world, whereas the combination of FGS and photodynamic therapy (PDT) has yet to reach clinical implementation and remains an active area of translational investigations. Two significant challenges to the clinical translation of PDT for brain cancer are as follows: (1) Limited light penetration depth in brain tissues and (2) Poor selectivity and delivery of the appropriate photosensitizers. To address these shortcomings, we developed nanoliposomal protoporphyrin IX (Nal-PpIX) and nanoliposomal benzoporphyrin derivative (Nal-BPD) and then evaluated their photodynamic effects as a function of depth in tissue and light fluence using rat brains. Although red light penetration depth (defined as the depth at which the incident optical energy drops to 1/e, ~37%) is typically a few millimeters in tissues, we demonstrated that the remaining optical energy could induce PDT effects up to 2 cm within brain tissues. Photobleaching and singlet oxygen yield studies between Nal-BPD and Nal-PpIX suggest that deep-tissue PDT (>1 cm) is more effective when using Nal-BPD. These findings indicate that Nal-BPD-PDT is more likely to generate cytotoxic effects deep within the brain and allow for the treatment of brain invading tumor cells centimeters away from the main, resectable tumor mass.     

Stability of a Crank–Nicolson pressure correction scheme based on staggered discretizations

In the context of LES of turbulent flows, the control of kinetic energy seems to be an essential requirement for a numerical scheme. Designing such an algorithm, that is, as less dissipative as possible while being simple, for the resolution of variable density Navier–Stokes equations is the aim of the present work. The developed numerical scheme, based on a pressure correction technique, uses a Crank–Nicolson time discretization and a staggered space discretization relying on the Rannacher–Turek finite element. For the inertia term in the momentum balance equation, we propose a finite volume discretization, for which we derive a discrete analogue of the continuous kinetic energy local conservation identity. Contrary to what was obtained for the backward Euler discretization, the dissipation defect term associated to the Crank–Nicolson scheme is second order in time. This behavior is evidenced by numerical simulations. Copyright © 2013 John Wiley & Sons, Ltd.     

Multi-Technique Analysis of Soot Reactivity from Conventional and Paraffinic Diesel Fuels

A 2.0 L, 4-cylinder, turbocharged, common rail diesel engine was used for generating soot samples. Three fuels were tested: a “first fill” diesel fuel, a gas-to-liquid fuel (GTL) and a hydrotreated fuel derived from vegetable oils (HVO). A stationary low-load operating mode (1667 rpm and 78 Nm) was selected for testing, and some modifications in the injection process (strategy, timing and pressure) were evaluated experimentally to assess their influence in the soot reactivity. The collected soot samples were characterized using a thermogravimetric analyzer (TGA), a differential scanning calorimeter (DSC), a diffuse reflectance infrared Fourier transform spectrometer (DRIFTS) and a surface area analyzer. All techniques anticipated that HVO and GTL soot samples are more reactive (i.e. show higher potential to be oxidized at lower temperatures leading to more efficient regeneration processes in a Diesel Particle Filter – DPF) compared to diesel soot. Additionally, the four characterization techniques showed the same tendencies when analyzing the effect of the engine operating parameters. In view of the results, the paraffinic fuels – HVO and GTL – here tested confirm their promising perspective for future use in automotive diesel engines, while some guides are proposed to enhance the soot reactivity via calibration of engine operating parameters.     

Cahn–Hilliard/Navier–Stokes Model for the Simulation of Three-Phase Flows

In this article, we describe some aspects of the diffuse interface modelling of incompressible flows, composed of three immiscible components, without phase change. In the diffuse interface methods, system evolution is driven by the minimisation of a free energy. The originality of our approach, derived from the Cahn–Hilliard model, comes from the particular form of energy we proposed in Boyer and Lapuerta (M2AN Math Model Numer Anal, 40:653–987,2006), which, among other interesting properties, ensures consistency with the two-phase model. The modelling of three-phase flows is further completed by coupling the Cahn–Hilliard system and the Navier–Stokes equations where surface tensions are taken into account through volume capillary forces. These equations are discretized in time and space paying attention to the fact that most of the main properties of the original model (volume conservation and energy estimate) have to be maintained at the discrete level. An adaptive refinement method is finally used to obtain an accurate resolution of very thin moving internal layers, while limiting the total number of cells in the grids all along the simulation. Different numerical results are given, from the validation case of the lens spreading between two phases (contact angles and pressure jumps), to the study of mass transfer through a liquid/liquid interface crossed by a single rising gas bubble. The numerical applications are performed with large ratio between densities and viscosities and three different surface tensions.