Application of Silver(II) Difluoride in Organic Synthesis

Fluorinated compounds often possess valuable properties, such as increased metabolic stability, increased lipophilicity, and high oxidative stability. Therefore, chemists are seeking to master more synthesis methodology to access various fluorinated compounds. Silver(II) difluoride is a unique fluorinating compound which has a relatively high oxidizing ability. It enables some difficult fluorinations on certain systems, such as benzene, pyridine, etc. However, due to its high reactivity, its chemoselectivity is low. Part of our research goal is to control the reaction condition so that the selectivity could be enhanced. Gratifyingly, three different substrate categories were discovered to perform in a synthetically useful manner by our group. Cyclopropanols were fragmented to β-fluoroketones, alkyl tertiary bromides were transformed to alkyl tertiary fluorides, and benzofurans were converted to 2,3-difluoro-2,3-dihydrobenzofurans. In all the three cases, cryogenic conditions were applied in order to avoid side reactions. Synthetic applications were made to demonstrate the fluorinated products could participate in different synthetic routes.