Development and application of decatungstate catalyzed C-H 18F- and 19F-fluorination, fluoroalkylation and beyond

Abstract

Over the past few decades, photocatalytic C-H functionalization reactions have received increasing attention due to the often mild reaction conditions and complementary selectivities to conventional functionalization processes. Now, photocatalytic C-H functionalization is a widely employed tool, supporting activities ranging from complex molecule synthesis to late-stage structure-activity relationship studies. In this perspective, we will discuss our efforts in developing a photocatalytic decatungstate catalyzed C-H fluorination reaction as well as its practical application realized through collaborations with industry partners at Hoffmann-La Roche and Merck, and extension to radiofluorination with radiopharmaceutical chemists and imaging experts at TRIUMF and the BC Cancer Agency. Importantly, we feel that our efforts address a question of utility posed by Professor Tobias Ritter in “Late-Stage Fluorination: Fancy Novelty or Useful Tool?” (ACIE, 2015, 54, 3216). In addition, we will discuss decatungstate catalyzed C-H fluoroalkylation and the interesting electrostatic effects observed in decatungstate-catalyzed C-H functionalization. We hope this perspective will inspire other researchers to explore the use of decatungstate for the purposes of photocatalytic C-H functionalization and further advance the exploitation of electrostatic effects for both rate acceleration and directing effects in these reactions.