Catalytic Nucleophilic C(sp 3 )─H Functionalization/C─S Coupling via Iron Nitrenoids

Iron‐catalyzed C(sp 3 )─heteroatom coupling reactions provides an attractive strategy for constructing complex molecules from readily available electrophiles. Although iron catalysis, particularly via iron nitrenoids, has been well established for C(sp 3 )─H activation and C─N bond formation, C─S formation through C(sp 3 )─H activation has remained elusive. This challenge arises from the susceptibility of sulfur nucleophiles to oxidation, their strong tendency to poison metal catalysts, and the high stability of metal–thiolate complexes. In this study, we report an iron‐catalyzed nucleophilic C(sp 3 )─H activation/C─S coupling via iron nitrenoids, employing dioxazolones as nitrene precursors in conjunction with nucleophilic substitution by sulfur nucleophiles. To enable the use of sulfur nucleophiles in oxidative C(sp 3 )─H functionalization reactions, we developed a rationally designed phthalocyanine iron(II) catalytic system. Without the need for pre‐functionalized sulfur reagents, a wide range of sulfur‐containing moieties, including complex drug molecules, can be introduced, highlighting its utility in organic synthesis and drug development. Mechanistic studies revealed that electron‐withdrawing substituents on the catalyst framework play a crucial role in suppressing undesired hydrogen atom transfer events associated with thiol species that promotes the C─S bond formation.