Efficient Pd-Catalyzed Heterobenzylic Cross-Coupling Using Sulfonium Salts as Substrates and (PhO)(3)P as a Supporting Ligand.

S-(2-Furanylmethyl)tetramethylenesulfonium hexafluorophosphate, S-(2-thienylmethyl)tetramethylenesulfonium hexafluorophosphate, S-(3-thienylmethyl)tetramethylenesulfonium hexafluorophosphate, and S-(N-tert-butoxycarbonyl-2-pyrrolylmethyl)tetramethylenesulfonium hexafluorophosphate have been conveniently prepared from the corresponding alcohols. These stable heterobenzylic sulfonium salts participate in palladium-catalyzed Stille cross-couplings with organostannanes. All but the last mentioned sulfonium salt are also active participants in palladium-catalyzed cross-coupling reactions with boronic acids and organozinc halides. Because the heterobenzylic cross-coupling reactants are potent alkylating agents, they scavenge the typical phosphines and arsines that otherwise could be used to stabilize the palladium catalyst over extended reaction times. This problem was overcome by the use of (PhO)(3)P as a unique supporting ligand for the palladium-catalyzed cross-coupling of heterobenzylic sulfonium salts.