Enrique Vazquez

Dynamic Kinetic Resolution: Asymmetric Transfer Hydrogenation of α-Alkyl-Substituted β-Ketoamides

Dynamic kinetic resolution (deracemization) of various alpha-alkyl-substituted beta-ketoamides 1 via asymmetric transfer hydrogenation proceeded efficiently to give the corresponding syn-beta-hydroxy amides 3 in high diastereo- and enantioselectivities. Specifically, subjection of 1 to HCO(2)H and Et(3)N in the presence of 0.5-1 mol % of pentafluorobenzenesulfonyl-DPEN-Ru catalyst 2b at 30-40 degrees C in either PhCH(3) or CH(2)Cl(2) generated the syn-hydroxy product 3 selectively in 15-33:1 dr, 93-97% ee, and 75-88% isolated yields.

Reactive resin facilitated preparation of an enantiopure fluorobicycloketone

A facile preparation of enantiopure ethyl (1S,5S,6S)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate is described. The key feature of the synthesis involves copper-catalyzed enantioselective intramolecular cyclopropanation of a diazoketone to form endo-fluorocyclopropane in a single operation. Removal of a problematic chloroketone impurity using a reactive resin treatment enabled a high throughput enantiopurity upgrade by chiral HPLC. The development of a scalable synthesis of is presented, including details of the selection of catalyst and ligand optimization, incorporation of a reactive resin treatment and selection of chiral HPLC media and conditions.

Evaluation of core-shell particle columns for ion-pair reversed-phase liquid chromatography analysis of oligonucleotides.

An investigation into the use of core-shell particle columns for separation of short (∼21 base pairs) RNA oligonucleotides by ion-pair reversed-phase liquid chromatography (IP-RPLC) showed improved resolution for a number of test analytes relative to conventional (fully-porous) reversed-phase columns. The best resolutions were obtained using columns packed with smaller sub-2μm core-shell particles.