Type

Text

Type

Dissertation

Advisor

Parker, Kathlyn | Ngai, Ming Y | Lauher, Joseph | Concepcion, Javier

Date

2017-12-01

Keywords

Chemistry | arene | fluorine | ketyl | radical | rearrangement | trifluoromethoxylation

Department

Department of Chemistry

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/78233

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Carbon-carbon and carbon-heteroatom bond-forming reactions lie at the heart of synthetic organic chemistry. They allow construction of complex molecular frameworks and introduction of new substituents. Despite the tremendous progress in the area over the past decades, there has been a growing demand for development of novel methods to construct C–C and C–X bonds under mild and eco-compatible reaction conditions. In order to form a new C–C bond without using stoichiometric amounts of toxic and unstable reagents, we developed a photocatalytic protocol for the coupling between alkenylpyridines and carbonyl derivatives with a Lewis acid co-catalyst. Our synergistic catalytic system facilitates the formation of alcohols and amines under mild reaction conditions and tolerates a wide scope of functional groups. Our protocol is exclusively β-selective, and thus offers a complementary method to the existing β-selective reductive coupling reactions of alkenylpyridines. The mechanistic studies indicate that the key step involves addition of ketyl or α-aminoalkyl anion radicals to Lewis acid-activated alkenylpyridines. Due to the alteration of the natural reactivity pattern of carbonyl derivatives under the reaction conditions, we anticipate that this transformation will serve as the basis for the development of novel coupling reactions of two electrophiles. With regard to C–X bond formation, we successfully established an intramolecular trifluoromethylation reaction of (hetero)arenes. Prior to our report, the synthesis of OCF3–bearing heterocycles under mild conditions had remained elusive, and trifluoromethoxylated heteroarenes were extremely rare. We demonstrated that our method enables formation of trifluoromethoxylated (hetero)arenes in good to excellent yields, exhibits high functional group tolerance, is highly ortho-selective, operationally simple, and amenable to scale-up. We believe that our strategy would enable easy access to trifluoromethoxylated organic molecules that otherwise would be difficult or impossible to make. We envision that our method would be employed in the synthesis of bioactive molecules and hence accelerate drug discovery and development process. | 335 pages

Download

Share

COinS