Rapid Access to Isoprenoid Quinones through X@RONa-Catalyzed Redox Chain Reaction.

Dodecameric sodium alkoxide clusters encaging a halide anion (X@RONa) were shown to be C-C bond formation catalysts in the redox chain reaction of quinones. With up to 30 mol % tert-decanol as the catalyst and stoichiometric base NaH, a great number of chemically sensitive isoprenoid quinones, including health-relevant Coenzyme Q and Vitamin K family compounds, were easily made in one step from their parent quinones and polyprenyl halide. The X@RONa clusters and possible cluster-derived intermediates were studied by characterization techniques, control experiments, and theory. The X@RONa clusters likely facilitated the C-alkylation step by preventing O-alkylation, promoting dissociation of halide from the alkyl chain, and transporting hydride into the nonpolar solvent.

Kinetic Resolution of Sulfoximines via Asymmetric Organocatalyzed Formation of Benzothiadiazine-1-oxides.

A catalytic kinetic resolution of sulfoximines has been developed through chiral phosphoric acid-catalyzed intramolecular dehydrative cyclizations. A variety of racemic sulfoximines bearing an ortho-amidophenyl moiety underwent asymmetric dehydrative cyclizations using this method, yielding both the recovered sulfoximines and benzothiadiazine-1-oxide products with good to high enantioselectivities (with s-factor up to 61). The diverse derivatizations of the chiral products into a wide range of S-stereogenic center-containing S,N-heterocycles have demonstrated the value of this method.

Enantioselective Dearomatization of Substituted Phenols via Organocatalyzed Electrophilic Amination.

Highly efficient and stereoselective dearomatization of substituted phenols was achieved via chiral phosphoric acid-catalyzed electrophilic para-amination with commercially available azodicarboxylates. This protocol readily afforded a series of chiral 2,5-cyclohexadienones bearing 4-aza-quaternary stereocenters with excellent yields and enantioselectivities (≤99% yield and >99% ee). Easy scale-up of this reaction to a gram scale and diverse derivatizations of the chiral products into α-tertiary amines and α-tertiary heterocycles derivatives well demonstrated the potential of this method.

Asymmetric Enamide-Imine Tautomerism in the Kinetic Resolution of Tertiary Alcohols.

An efficient protocol for kinetic resolution of tertiary alcohols has been developed through an unprecedented asymmetric enamide-imine tautomerism process enabled by chiral phosphoric acid catalysis. A broad range of racemic 2-arylsulfonamido tertiary allyl alcohols could be kinetically resolved with excellent kinetic resolution performances (with s-factor up to >200). This method is particularly effective for a series of 1,1-dialkyl substituted allyl alcohols, which produced chiral tertiary alcohols that would be difficult to access via other asymmetric methods. Facile and versatile transformations of the chiral α-hydroxy imine and enamide products, especially the efficient stereodivergent synthesis of all four stereoisomers of ß-amino tertiary alcohols using one enantiomer of the catalyst, demonstrated the value of this kinetic resolution method.

Asymmetric Aza-Diels-Alder Reactions of in Situ Generated ß,ß-Disubstituted α,ß-Unsaturated N-H Ketimines Catalyzed by Chiral Phosphoric Acids.

A novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters has been realized by asymmetric aza-Diels-Alder reactions of 3-amido allylic alcohols with oxazolones enabled by chiral phosphoric acid catalysis. A series of aryl/alkyl- and alkyl/alkyl-disubstituted 3-amido allylic tertiary alcohols and 4-substituted oxazolones could be well tolerated in these reactions, producing dihydropyridinones with excellent diastereoselectivities and high enantioselectivities. Mechanistic study and control experiments were performed to shed light on the reaction mechanism, in which a configurationally defined ß,ß-disubstituted α,ß-unsaturated N-H ketimine was proposed as the key intermediate.