C(sp3) Cross-Couplings of Benzyl and Tertiary Halides with Thiols or Alcohols Catalyzed by Iron

Various metal catalysts have proven effective in carbon–heteroatom bond formation with softer heteroatomic nucleophiles, but examples remain largely limited to sp2 hybridized carbon electrophiles. Here, we report the coupling of sp3 hybridized benzyl or tertiary halides with soft thiol nucleophiles catalyzed by iron. The reaction is broad in substrate scope for both coupling partners and applicable in the construction of congested tri- and tetrasubstituted carbon-centers as well as beta-quaternary thioethers. The synthetic utility is further emphasized by the coupling of alcohol nucleophiles, gram-scale synthesis, thiol bioconjugation, and rapid herbicide library synthesis. Results from mechanistic experiments are consistent with a stereoablative pathway that likely involves a carbon radical intermediate. Overall, we provide an efficient method to prepare pharmaceutically and materially relevant carbon–sulfur and carbon–oxygen bonds by expanding iron-catalyzed cross-coupling reactions to the coupling of sp3 hybridized carbon electrophiles with soft nucleophiles.