Copper(I) Iodide Polyphosphine Adducts at Low Loading for Sonogashira Alkynylation of Demanding Halide Substrates: Ligand Exchange Study between Copper and Palladium

The prestabilization of copper iodide with a multidentate ferrocenyl phosphine ligand promotes the palladium-catalyzed cross-coupling of demanding halides with phenylacetylene in a selective way. Novel CuI-triphosphine adducts are described in the solid state and in solution. Their use allowed the introduction of the copper iodide cocatalyst in unprecedented low amounts (0.4 to 0.1 mol %) in systems also employing low amounts of “ligand-free” [Pd^II(η³-allyl)Cl]₂ precursor (0.2 to 0.05 mol %). The scope of substrates is reported, and electronically or sterically deactivated bromides were efficiently coupled. Concerning aryl chlorides, electron-poor activated substrates were also coupled using this innovative low-metal-content catalytic system. Some rarely tackled mechanistic aspects are discussed herein. In particular, the transfer of ligand from copper to palladium monitored by NMR was found to be different depending on the polyphosphine ligand. The inhibition of diyne formation was also an interesting feature provided by the prestabilized copper species used in low amount, contrary to the employment of 5 mol % CuI with palladium. Notably, the copper(I) iodide phosphine adduct 6, formed from 1,2-bis(diphenylphosphino)-1′-(diisopropylphosphino)-4-tert-butylferrocene, also allowed under copper-only conditions the “palladium-free” coupling of the electron-rich deactivated 4-iodotoluene to phenylacetylene.