Advances in Selectivity of the Suzuki-Miyaura and Hofmann-Loffler-Freytag Reactions
Jeffrey Miles Blackburn, Ph.D. candidate
Jennifer Roizen, advisor
Monday, May 20, 2019 - 12:00pm to 2:00pm
Location: French Family Science Center 1243
Avery, Meg

The design of synthetic transformations that proceed selectively in the presence of multiple sites of similar chemical reactivity has been a long-standing challenge. Cross-coupling and C–H functionalization processes have gathered significant attention over the past few decades as a result of their ability to rapidly generate molecular complexity. Despite these advances, a chemist’s ability to judiciously, selectively, and predictably perform these synthetic transformations has not yet been fully realized. Iinvestigations into new methods for the Suzuki-Miyaura and Hofmann-Löffler-Freytag reactions that proceed with predictable selectivity will be discussed. 

Tactical advances have resulted in the development of selective, serial, and exhaustive cross-coupling transformations of alkyl pinacol boronic esters with polyhalogenated (hetero)arenes. These Suzuki-Miyaura processes facilitate access to a wide variety of alkyl-substituted aromatic compounds, specifically 2-alkylpyridines, which constitute an important class of functional molecules.

 Conceptual innovations have established sulfamate esters as a promising manifold for the radical-mediated functionalization of remote, aliphatic C–H bonds. New methods for the synthesis of sulfamate esters have facilitated access to these valuable functional motifs, thereby allowing their use in Hofmann-Löffler-Freytag reactions. Accordingly, the selective, sulfamate ester-guided chlorination of remote C(sp3)–H bonds has been developed. This transformation proceeds with unique site-selectivity and furnishes C(3)-functionalized masked alcohol derivatives.