Palladium(II)-Catalyzed Cyclization of Unsaturated Hydroperoxides for the Synthesis of 1,2-Dioxanes

The cyclization of γ,δ-unsaturated tertiary hydroperoxides in the presence of a palladium(II) catalyst afforded 1,2-dioxanes resembling biologically active natural products. A variety of substrates were screened, and synthetic manipulations were accomplished to construct compounds with structural similarity to antimalarial targets

Kinetic Resolution of Hydroperoxides with Enantiopure Phosphines: Preparation of Enantioenriched Tertiary Hydroperoxides

An efficient reductive kinetic resolution strategy capable of accessing optically active tertiary hydroperoxides is reported. Readily accessible tertiary hydroperoxides are resolved with commercially available (R)- or (S)-xylyl-PHANEPHOS with selectivity factors as large as 37. The resulting bis(phosphine oxide) can be recycled in high yields. The isolated mono(phosphine oxide) intermediate resolved hydroperoxides with the same selectivity as the parent bisphosphine

Phosphine-Catalyzed Reductions of Alkyl Silyl Peroxides by Titanium Hydride Reducing Agents: Development of the Method and Mechanistic Investigations

A method that allows for the reduction of protected hydroperoxides by employing catalytic amounts of phosphine is presented. The combination of a titanium(IV) alkoxide and a siloxane allowed for the chemoselective reduction of phosphine oxides in the presence of alkyl silyl peroxides. Subsequent reduction of the peroxide moiety by phosphine provided the corresponding silylated alcohols in useful yields. Mechanistic experiments, including crossover experiments, support a mechanism in which the peroxide group was reduced and the silyl group was transferred in a concerted step. Labeling studies with 17O-labeled peroxides demonstrate that the oxygen atom adjacent to the silicon atom is removed from the silyl peroxide

Lactams as EP₄ Prostanoid Receptor Agonists. 3. Discovery of <i>N</i>-Ethylbenzoic Acid 2-Pyrrolidinones as Subtype Selective Agents

Two distinct synthetic schemes were applied to access heteroatom-containing α-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. γ-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3