Executive Summary : | Fluorine-containing organic compounds and building blocks are crucial in organic chemistry, with over 40% of agrochemicals and 20% of pharmaceuticals containing a fluorinated motif. The use of fluorine atoms in medicinal chemistry increases drug lipophilicity and metabolic stability. Selective fluorination approaches have become a useful tool to address challenges in organic and medicinal chemistry. However, synthesizing fluorinated pharmaceutical building blocks and active agrochemical intermediates remains a significant challenge. Selective fluorination strategies using N-heterocyclic carbene (NHC) organocatalysis and aryne chemistry for the construction of fluorinated aromatic compounds are proposed. These strategies involve selective beta-fluorination and remote fluorination of carbonyl compounds, and the use of arynes as aryl sources for fluorinated aromatic compounds. Various methods for proximal and distal fluorination using NHC organocatalysis have been described, with the strategy planned to extend to selective trifluoromethyl(thiol)ation reactions. If successful, this could result in complex fluorinated cyclic and acyclic derivatives, which are difficult to synthesize using conventional methods. NHC-catalyzed fluorination could be applied for the synthesis of fluorinated Lacosamide, 5-fluorouracil, and trifluoromethyl-containing aminophenol. A strategy for the synthesis of potent antibacterial agent enoxacin is proposed using the merger of aryne chemistry with fluorine chemistry. |