Palladium-meta-terarylphosphine catalyst for the Mizoroki-Heck reaction of (hetero)aryl bromides and functional olefins.

The evolutionary meta-terarylphosphine ligand architecture of Cy*Phine was recently shown to be a key feature that imposed outstanding performance in palladium-catalyzed copper-free Sonogashira applications. Herein, the Pd-Cy*Phine combination has similarly proven to be a powerful catalyst system for the Mizoroki-Heck reaction. Using high-throughput screening (HTS) methodology, DMF and NaHCO3 were rapidly identified as the most effective solvent and base pair for the cross-coupling catalysis of challenging and industrially valuable substrates including highly electron-rich heteroaryl bromides and unactivated olefins. Unprotected functional groups were well tolerated using low catalyst loadings, and the simple protocol produced excellent yields (up to 99%) with unprecedented substrate diversity. The Pd-Cy*Phine system broadly outperformed many state-of-the-art commercial alternatives, which demonstrated its potential as a next-generation cross-coupling catalyst.

Desymmetrization of diolefinic diols by enantioselective amino-thiocarbamate-catalyzed bromoetherification: synthesis of chiral spirocycles.

A facile, efficient, and highly diastereo- and enantioselective bromoetherification of diolefinic diols has been developed using an amino-thiocarbamate catalyst. Further manipulations of the bromoether products enabled entry into a new class of spirocycles which are distinctively lacking in the literature.

Enantioselective synthesis of 2-substituted and 3-substituted piperidines through a bromoaminocyclization process.

A catalytic enantioselective bromocyclization of olefinic amides using amino-thiocarbamates as the catalysts has been developed. The resulting enantioenriched 2-substituted 3-bromopiperidines can readily be transformed to 3-substituted piperidines through a silver salt-mediated rearrangement. This process has been applied to the synthesis of a dopaminergic drug, Preclamol.

Lewis basic selenium catalyzed chloroamidation of olefins using nitriles as the nucleophiles.

A Lewis base catalyzed chloroamidation of olefinic substrates was achieved using diphenyl selenide as the catalyst. The reaction conditions are mild and suitable for a wide range of substrates including those which are acid labile.