N2Phos - an easily made, highly effective ligand designed for ppm level Pd-catalyzed Suzuki-Miyaura cross couplings in water

Abstract

A new biaryl phosphine-containing ligand from an active palladium catalyst for ppm level Suzuki-Miyaura couplings, enabled by an aqueous micellar reaction medium. A wide array of functionalized substrates including aryl/heteroaryl bromides are amenable, as are, notably, chlorides. The catalytic system is both general and highly effective at low palladium loadings (1000-2500 ppm or 0.10-0.25 mol%). Density functional theory calculations suggest that greater steric congestion in N2Phos induces increased steric crowding around the Pd center, helping to destabilize the 2?:?1 ligand-Pd(0) complex more for N2Phos than for EvanPhos (and less bulky ligands), and thereby favoring formation of the 1?:?1 ligand-Pdocomplex that is more reactive in oxidative addition to aryl chlorides.