The arylation of sp3-hybridized C-H's bonds is a powerful strategy to build molecular complexity and diversity. A novel and efficient palladium-catalyzed direct sp3 C-H arylation of aryl and alkyl benzyl thioether derivatives with aryl bromides is reported. The reaction involves reversible deprotonation of the benzylic C-H's of the thioether with either LiN(SiMe3)2 or NaN(SiMe3)2 and subsequent cross-coupling to provide the functionalized products in up to 97% yield. A screen of 24 of the most successful ligands in cross-coupling chemistry led to the identification of NiXantPhos as the only viable ligand for this challenging coupling.
Keywords: Arylation; Cross-Coupling; C–H functionalization; Palladium; Sulfides.