Development of decarboxylative strategies towards the synthesis of fluorinated pharmacons

Fluoro(oxo) functional groups, such as trifluoromethyl ketones, difluoromethyl ketones, and trifluoroethanols, have emerged as desirable motifs in medicinal chemistry for the fine tuning of pharmacokinetic properties. Over the past few decades, fluoro(oxo) diversity has been accessed through oxidation state manipulations from the parent trifluoromethyl ketone, either by carbonyl reduction to give the trifluoroethanol or elimination to yield the difluoromethyl ketone. As such, synthetic chemists are interested in harnessing catalytic methods by virtue of its ability to lower kinetic barriers and enable otherwise challenging transformations. In this context, our interest in the preparation of fluorinated molecules has led us to harness readily available and stable fluorinated building blocks as redox-active reagents for C–C bond forming reactions. In this thesis, I will describe our group’s effort towards using oxidation-first and reduction-first photochemical methods for the selective activation of fluorinated feedstocks. In addition, I will describe our efforts towards a divergent decarboxylation approach for a diversity-oriented synthesis of fluorinated pharmacons.