Palladium Theory of Aqueous-Phase Heck Alkynylations

The influence of water on the catalysis of biphasic Heck alkynylation, a family of palladium-catalyzed carbon-carbon bond formations that enable materials, natural products, and pharmaceuticals syntheses, was investigated.  Kinetic theory derived from Hatta moduli and pseudo-stationary-state approximations discovered the biphasic cross-coupling to occur within thin films of immiscible aqueous-organic interfaces.  Remarkably, water reduced Gibbs activation barriers compared to values previously estimated by density functional theory calculations (DFT) of purely organic syntheses.  Quantum tunneling in proton transfer mechanisms partly accounts for the change.  Water also influenced the rate-determining steps of the catalytic cycles, and it potentially switched the cross-coupling’s mechanism from deprotonation, previously thought to govern the reaction, to carbopalladation.  Carbopalladation theory identified the ~35% of the Pd wasted during synthesis was ~10% greater than the amount predicted by deprotonation.  Our discoveries enabled E-factor predictions that could someday help reduce chemical wastes generated during materials, natural products, and pharmaceutical manufactures.