Approaches to valuable halogenated products using radical-polar crossover catalysis or halogen transfer to arynes

Abstract

Molecules with halogen atoms have many applications. In direct applications, halogenated molecules are seen in many marketed pharmaceuticals and continue to represent a growing proportion year-to-year. They also find applications in agrochemicals, polymers, and materials, and the unique properties halogenation imparts to products has been difficult to replicate by other means. Additionally, halogen-containing molecules have indirect applications for many more products because a halogen-free chemical may succeed from a synthetic intermediate containing a halogen atom. Through reactions such as Pd-catalyzed couplings, halogenated materials have become a regular feature in molecular syntheses. Thus, the synthesis of halogen-containing molecules is a vital part toward supporting the growth of the pharmaceuticals, agrochemicals, and materials industries. New methods to access these products in a more efficient manner benefits many industries. This dissertation discusses two distinct strategies to synthesize valuable halogenated products. First, the application of redox-active ligands with transition-metal catalysis is considered especially with early transition metals. The combination of redox-active ligands with relatively redox-innocent early transition metals enabled a method for synthesis of gem-difluorostyrenes. This process occurs via radical-polar crossover, a mechanism new to early-transition metals. Second, synthesis of halogen-containing products was shown by exploiting known reactivity of arynes. This method involves functionalization with amine nucleophiles followed by a rapid halogen-transfer that competes with other undesirable pathways.