Design, Testing and Kinetic Analysis of Bulky Monodentate Phosphorus Ligands in the Mizoroki-Heck Reaction

A series of new monodentate phosphane ligands 2 have been evaluated in the MizorokiHeck arylation reaction of iodobenzene and styrene and compared with our previously reported ligands, 1, 3 and 4. The concept of rational ligand design is discussed, and we describe how the performance of this new ligand family could be predicted. Employing our best ligand, 3,3'-di-tert-butyl-5,5'-dimethoxybiphenyl-2,2'-diyl diisopropylphosphoramidite (3b), we explored the scope of the reaction with regards to solvent and the substrate. We also investigated the electronic dependence of the reaction by analysing the relationship between the rate and Hammett constant. Sufficient steric bulk is required to enforce the catalytic reaction to proceed through the mono-coordinated palladium species, thereby increasing its reactivity. The electronic properties determine the concentration of the active species from the monomer dimer equilibrium and their intrinsic reactivity. The cyclic phosphoramidite 3b provides an optimum in both properties within the systems studied, resulting in a rate limiting migratory insertion step.