Asymmetric synthesis of novel spirocycles via a chiral phosphoric acid catalyzed desymmetrization

A straightforward method for the asymmetric preparation of novel lactone and lactam spirocycles is described. An initial desymmetrization via a chiral Brønsted acid yields enantioenriched lactones which readily undergo a second cyclization to give the desired spirocycle.     

Screening of Three Transition Metal‐Mediated Reactions Compatible with DNA‐Encoded Chemical Libraries

The construction of DNA‐encoded chemical libraries (DECLs) crucially relies on the availability of chemical reactions, which are DNA‐compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium‐catalyzed reactions (Suzuki cross‐coupling, Sonogashira cross‐coupling, and copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.     

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P₁ agonist precursor developed by Merck.     

Approaches to Modeling Bed Drag in Pine Forest Litter for Wildland Fire Applications

Transport in Porous Media - Modeling flow in vegetative fuel beds is a key component in any detailed physics-based tool for simulating wildland fire dynamics. Current approaches for drag modeling,...     

Nowcasting Avalanches as Earthquakes and the Predictability of Strong Avalanches in the Olami-Feder-Christensen Model

Nowcasting earthquakes, suggested recently as a method to estimate the state of a fault and hence the seismic risk, is based on the concept of natural time. Here, we generalize nowcasting to a prediction method the merits of which are evaluated by means of the receiver operating characteristics. This new prediction method is applied to a simple (toy) model for the waiting (natural) time of the stronger earthquakes, real seismicity, and the Olami-Feder-Christensen earthquake model with interesting results revealing acceptable to excellent or even outstanding performance.     

Nickel‐Catalyzed Cross‐Electrophile Coupling with Organic Reductants in Non‐Amide Solvents

Cross‐electrophile coupling of aryl halides with alkyl halides has thus far been primarily conducted with stoichiometric metallic reductants in amide solvents. This report demonstrates that the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic reductant enables the use of non‐amide solvents, such as acetonitrile or propylene oxide, for the coupling of benzyl chlorides and alkyl iodides with aryl halides. Furthermore, these conditions work for several electron‐poor heterocycles that are easily reduced by manganese. Finally, we demonstrate that TDAE addition can be used as a control element to ‘hold’ a reaction without diminishing yield or catalyst activity.