Chalcogen OCF 3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities

The synthesis of SCF 3 as well as SeCF 3 isosteres of two OCF 3 ‐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 SCF 3 and SeCF 3 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‐CF 3 groups as potential key players for future fluorinated pharmaceuticals.