Mechanistic Model for Enantioselective Intramolecular Alkene Cyanoamidation via Palladium-Catalyzed C-CN Bond Activation.

We studied key aspects of the mechanism of Pd-catalyzed C-CN bond activation and intramolecular enantioselective alkene cyanoamidation. An Abboud-Abraham-Kamlet-Taft (AAKT) linear solvation energy relationship (LSER) model for enantioselectivity was established. We investigated the impact of Lewis acid (BPh), Lewis base (DMPU), and no additives. BPh additive led to diminished enantioselectivity and differing results in CN crossover experiments, initial rate kinetics, and natural abundance C/C kinetic isotope effect measurements. We propose two catalytic mechanisms to account for our experimental results. We propose that the DMPU/nonadditive pathway passes through a κ-phosphoramidite-stabilized Pd intermediate, resulting in high enantioselectivity. BPh prevents the dissociation of CN, leading to a less rigid κ-phosphoramidite-neutral Pd intermediate.