Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst.

We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines.

Lewis Base/Bronsted Acid Dual-Catalytic C-H Sulfenylation of Aromatics.

A Lewis base/Bronsted acid catalyzed aromatic sulfenylation is reported. These studies demonstrated that the incorporation of electron-rich sulfenyl groups proceeded in the absence of a Lewis base, with kinetic studies indicating an autocatalytic mechanism. The incorporation of electron-poor sulfenyl groups demonstrated little autocatalysis necessitating the use of a Lewis base.

Enantioselective Synthesis of Pyrrolopyrimidine Scaffolds through Cation-Directed Nucleophilic Aromatic Substitution.

The catalytic enantioselective synthesis of 3-aryl-substituted pyrrolopyrimidines (PPYs), a common motif in drug discovery, is achieved through a kinetic resolution via quaternary ammonium salt-catalyzed nucleophilic aromatic substitution (SAr). Both enantioenriched products and starting materials can be functionalized with no observed racemization to give enantiodivergent access to diverse chiral analogues of an important class of kinase inhibitor. One of the compounds was found to be a potent and selective inhibitor of breast tumor kinase.

A conjugate Lewis base-Brønsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions.

Catalysts that contain a thiourea tethered to a carboxylic acid were found to affect the sulfenylation of indoles and other N-heterocycles on the hour time scale at room temperature. The mild nature of these conditions allowed for the incorporation of diverse functionalities into more complex heterocycles.

A practical Lewis base catalyzed electrophilic chlorination of arenes and heterocycles.

A mild phosphine sulfide catalyzed electrophilic halogenation of arenes and heterocycles that utilizes inexpensive and readily available N-halosuccinimides is disclosed. This methodology is shown to efficiently chlorinate diverse aromatics, including simple arenes such as anthracene, and heterocycles such as indoles, pyrrolopyrimidines, and imidazoles. Arenes with Lewis acidic moieties also proved amenable, underscoring the mild nature of this chemistry.