Quantitative Evaluation of the Factors Contributing to the “Copper Effect” in the Stille Reaction

The relative importance of the factors contributing to the accelerating effect of CuI on [PdL4]-catalyzed couplings of R1I and R2SnBu3 (copper effect) has been quantitatively evaluated in THF for R1 = 3,5-C6Cl2F3; R2 = vinyl, C6H4-4-OMe; L = AsPh3, PPh3, using spectroscopic and kinetic methods. The 19F NMR kinetic data show that the rate enhancement produced by addition of CuI is strongly related with the "autoretardation" effect intrinsic to [PdL4] catalysts and is almost independent of the organotin reagent (vinyl, aryl). The "autoretardation" is due to the release of 2 equiv of L during the oxidation of [PdL4] to yield trans-[PdR1IL2], which is the species undergoing transmetalation. CuI does not promote the dissociation of L from trans-[PdR1IL2], but it captures part of the free neutral ligand L and therefore mitigates the autoretardation produced by the presence of free L on the rate-determining associative transmetalation. In the conditions studied (Pd:Cu = 1:2; T = 322.6 K; THF as solvent), for L = AsPh3 the CuI added captures about 25% of the free AsPh3 and the copper effect compensates only ca. 1% of the autoretardation, whereas for L = PPh3 the CuI captures about 99% of the free PPh3 and the compensation is about 30%. This remarkable variation is caused by the combined effect of two independent factors: (i) The catalyst [Pd(PPh3)4] is more autoretarded than [Pd(AsPh3)4]; and (ii) CuI is a more effective scavenger for PPh3 than for AsPh3.