Emerging fluorination methods in organic chemistry relevant for life science application

Abstract The benefits of fluorine incorporation into biologically active molecules are well documented, and, at the current time, approximately 25% of pharmaceuticals on the market and within development pipelines contain at least one fluorine atom. Over the last decade, advances in fluorination methodologies have significantly expanded the toolbox of the medicinal chemist. Recently developed mild reagents (i.e., Phenofluor and Pyfluor) and emerging technologies (in particular, selective C–H functionalization) have the potential to enable the rapid exploration of structure–activity relationships, the blocking of metabolic hot spots, and the preparation of biological probes. This chapter will describe recent advances in synthetic methods that effect the late-stage introduction of fluorine into complex drug-like molecules. Examples will illustrate how these approaches can be applied to accelerate drug-discovery efforts.