Aminoxyl derivatives as a versatile and sustainable platform to leverage fluorides in electrochemical fluorination reactions

"The introduction of fluorine into molecular scaffolds, while rare in nature, is a valuable transformation in the field of synthetic organic chemistry. Approximately 20% of marketed pharmaceuticals and 50% of agrochemicals introduced in the last 30 years contain at least one fluorine atom. Furthermore, fluorinated compounds, particularly those incorporating fluorine-18, are essential in positron emission tomography (PET) imaging. While traditional fluorination relied on highly reactive agents like F2, modern strategies favor milder, more selective reagents such as Selectfluor and NFSI, though these still depend on F2 for their preparation. Nucleophilic fluorinations using fluoride ions offer a complementary, more sustainable approach, yet remains underdeveloped compared to electrophilic methods. Building on this, our project aims to fully leverage fluorides as sustainable source of ""F""-atoms to (1) expand the scope of known accessible nucleophilic fluorination reactions of C-H bonds and (2) to develop new electrophilic fluorinating reagents which bypass the necessity of F2. To achieve aim 1 and 2 we will leverage aminoxyl-derivatives, such as TEMPO (tetramethyl-1-piperidinyloxy), bearing various steric and electronic substitutions in combination with electrochemical techniques. Particularly, the various aminoxyl derivatives will be electrochemically oxidized to the corresponding oxoammoniums, the key reactive species, which can either promote hydride transfer from C-H substrates (relevant to aim 1) or undergo nucleophilic attack by fluorides (relevant to aim 2) by modulating the electronic and steric properties. This research ultimate goal is to enable sustainable, metal-free electrochemical fluorination methods that bypass the need for F2, potentially transforming access to key fluorinated motifs in synthetic chemistry."