4-Pyridyl perfluoroalkyl sulfide as a practical nucleophilic perfluoroalkylation reagent

The incorporation of perfluoroalkyl groups into molecules leads to unique properties, and perfluoroalkylation reagents play a vital role in facilitating this process. Although various types of perfluoroalkylation reagents have been developed, the established nucleophilic perfluoroalkylation reagents have faced certain limitations. This work aims to address these challenges by introducing a novel nucleophilic perfluoroalkylation reagent, known as 4-pyridyl perfluoroalkyl sulfide (4-PySRf), which demonstrates a distinctive mechanism of perfluoroalkyl anion release based on the N-boryl pyridyl anion chemistry developed in our research group. In the presence of a diboron(4) compound and an alcoholate base, the 4-PySRf reagent efficiently undergoes perfluoroalkyl transfer reactions with a range of electrophiles. Unique to this reagent, compared to established nucleophilic perfluoroalkylation reagents, is its suitability for the effective transfer of functionalized perfluoroalkyl groups, as well as for intramolecular perfluoroalkylation reactions. Meanwhile, the 4-PySRf reagent exhibits excellent chemical stability, making it an ideal precursor for multi-step synthetic sequences. These attributes offer a robust strategy for synthesizing complex molecules incorporating perfluoroalkyl groups. Detailed mechanistic studies strongly support the nucleophilic nature of the perfluoroalkyl transfer reactions involving the 4-PySRf reagent. The present work expands the synthetic potential of the N-boryl pyridyl anion chemistry, and broadens the scope of nucleophilic perfluoroalkylation reactions.