<b>Radical Functionalization Reactions of </b><b><i>gem-</i></b><b>Difluoroalkenes and Palladium-Catalyzed C</b><b>-</b><b>H Functionalization of (Hetero)Arenes</b>

<p dir="ltr">The installation of fluorine and fluorinated moieties into molecules can perturb the physicochemical, pharmacokinetic, and pharmacodynamic properties of compounds relevant to the development of therapeutics, agrichemicals and biological probes. However, some fluorinated functional groups lie outside of current synthetic methodologies. To address the gap in synthetic methodology, our group exploits reactions of <i>gem-</i>difluoroalkenes as synthons for <i>gem-</i>difluoro-containing molecules. Although functionalization reactions of <i>gem-</i>difluoroalkenes are well known, these reactions typically result in a net C-F functionalization to deliver mono-fluorovinyl products. Thus, the work in the Altman lab is to develop hydro or difunctionalization reactions of <i>gem-</i>difluoroalkenes that avoid kinetically facile β-F elimination events from unstable anionic intermediates. One way to circumvent the β-F elimination pathway is through radical addition reactions, which avoid unstable anionic intermediates. Thus, this dissertation discusses two such processes: a peroxide initiated hydrophosphinylation of <i>gem-</i>difluoroalkenes (Chapter 2) and a palladium and copper co-catalyzed chloro-arylation reaction of <i>gem-</i>difluorostyrenes (Chapter 3).</p><p dir="ltr">C-H functionalization strategies enable rapid diversification of a wide array of substrates which are important in drug discovery, agrichemicals, and the pharmaceutical industry. In particular, the practical advantages of aryl C-H functionalization depends on the chemoselective activation of a single C-H bond over many others in a substrate (i.e. benzylic vs aryl <i>o</i>/<i>m</i>/<i>p</i>), which is challenging to control. Many attempts using pre-functionalized substrates have been reported, however, a method that delivers C-H functionalized products without bulky directing groups is scarce. Thus, this dissertation discusses two C-H functionalization reactions: a dearomatization and C-H functionalization of a substituted benzothiophene and a palladium-catalyzed para-selective C-H functionalization of arenes.</p>