Chalcogen OCF3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities

The synthesis of SCF3 as well as SeCF3 isosteres of two OCF3‐containing drugs was achieved through visible light and copper‐catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF3 and SeCF3 groups are more lipophilic than their oxygen counterpart; however, microsomal stability is unchanged, indicating that these molecular changes may be beneficial for in vivo half‐life. Enabled by modern synthetic methods, we present the chalcogen‐CF3 groups as potential key players for future fluorinated pharmaceuticals.