Catalytic Nucleophilic C(sp3)─H Functionalization/C─S Coupling via Iron Nitrenoids.

Iron-catalyzed C(sp3)─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(sp3)─H activation and C─N bond formation, C─S formation through C(sp3)─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(sp3)─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(sp3)─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.