Pd-Catalyzed C–H\nActivation vs β‑H\nElimination: An Experimental and Computational Insight into the Reactivity\nof Tertiary Alkylamines

Tertiary alkylamines can coordinate palladium salts and\ndirect\nC–H activation reactions. However, these tertiary alkylamines\ncan suffer from decomposition through oxidative pathways. This report\ndescribes the DFT analysis of acyclic and cyclic tertiary alkylamines\nwith respect to C–H bond cleavage through either γ-C(sp<sup>3</sup>)–H activation on the exo <i>N</i>-substituent\nor β-H elimination at the endocyclic position. The study assesses\nthe role of an <i>N</i>-acetyl amino acid ligand in suppressing\nthe β-H elimination pathway. Experiments using tertiary alkylamines\nwith isotopically labeled α-C–D bonds demonstrate the\nsmall differences in energy barriers that discern both reaction pathways.\nGuided by the insights of computational studies on methyl and strained\nmethylene γ-C–H activation in tertiary alkylamines, we\nreport a successful methine γ-C–H activation to construct\nring-strained quaternary centers through intermolecular C–H\narylation.