Palladium Theory of Aqueous‐Phase Heck Alkynylations for Intensification of Discovery and Manufacture

Abstract

AbstractThe influence of water on the catalysis of biphasic Heck alkynylation, a family of palladium‐catalyzed carbon‐carbon bond formations, was investigated. Kinetic theory derived from Hatta moduli and pseudo‐stationary‐state approximations discovered that water, in coordination, reductive elimination, and product dissociation reaction steps of the deprotonation catalytic cycle, increases Gibbs energy barriers compared to values previously estimated by density functional theory calculations of purely organic syntheses involving an aryl iodide. On the contrary, water reduces the energy barrier of reductive elimination in the carbopalladation catalytic cycle. Quantum tunneling in proton transfer mechanism might account for the change. The discoveries permitted E‐factor predictions that could someday help reduce chemical wastes generated during materials, natural products, and pharmaceutical manufactures. Theoretical groundwork is laid that enables data‐driven research in the academic laboratory and data‐driven development by the process chemist.