Development and Applications of an Amide Linchpin Reagent.

Linchpin reagents are building blocks that can be chemoselectively functionalized to afford products with a common, useful functional group. In this work, we describe the development and validation of the first amide linchpin reagent and demonstrate its use as a doubly electrophilic building block for the synthesis of a variety of amides, including challenging classes. The linchpin reagent was first functionalized via rhodium-catalyzed electrophilic amination.

Enabling Unfavorable Hydroamination Reactions Using a Chemoselective N-O Bond Reduction.

Despite major advances, intramolecular alkene hydroamination reactions often face limitations. Herein, a redox-enabled process featuring oxidation of an amine to a hydroxylamine, a concerted hydroamination step, followed by catalytic reduction of -oxide is shown to be broadly applicable. Catalyst screening and optimization showed that a KOsO(OH)-pinacol complex rapidly and chemoselectively reduces the -oxide cycloadduct in the presence of hydroxylamine and dimethyl sulfoxide.

Oxidative Syntheses of ,-Dialkylhydroxylamines.

Despite the wide utility of hydroxylamines in organic synthesis, relatively few are commercially available, and there is a need for direct, efficient, and selective methods for their synthesis. Herein, we report two complementary methods to accomplish direct oxidation of secondary amines using UHP as an oxidant. The first method uses 2,2,2-trifluoroethanol (TFE) and a large excess of amine.

Cope-Type Hydroamination of Vinylboronates.

Aminoboronic acid derivatives can serve as versatile synthetic intermediates and pharmacophores but remain difficult to synthesize. Herein we report a synthesis of the β-aminoboronic acid motif via anti-Markovnikov hydroamination of vinylboronates. This reaction benefits from the activating effect of the boronate substituent and forms novel BON-containing heterocycles, oxazaborolidine zwitterions.

Sphingosine Kinases Promote Ebola Virus Infection and Can Be Targeted to Inhibit Filoviruses, Coronaviruses, and Arenaviruses Using Late Endocytic Trafficking to Enter Cells.

Entry of enveloped viruses in host cells requires the fusion of viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. These viral fusion proteins need to be triggered by host factors, and for some viruses, this event occurs inside endosomes and/or lysosomes. Consequently, these 'late-penetrating viruses' must be internalized and delivered to entry-conducive intracellular vesicles.