Factors Impacting the Mechanism of the Mono-N-Protected Amino Acid Ligand-Assisted and Directing-Group-Mediated C–H Activation Catalyzed by Pd(II) Complex

Abstract

We computationally studied the roles of the (a) protecting group (PG), (b) side chain (R), and (c) length of amino acid backbone of the mono-N-protected amino acid (MPAA) ligand as well as (d) the nature of the substrate (DG-SUB) and directing group (DG) on the following elementary steps of the “N–H bond cleavage and subsequent C–H bond activation” mechanism for [MPAA]–Pd(II)-catalyzed C–H activation: (i) formation of the prereaction complex, [MPAA]–Pd(II)–[DG-SUB], with a weakly coordinated monoanionic amino acid ligand; (ii) N–H bond cleavage and formation of the catalytically active intermediate, [MPAA′]–Pd(II)–[DG-SUB], with a bidentately coordinated dianionic amino acid ligand, and (iii) C–H bond activation in [MPAA′]–Pd(II)–[DG-SUB] occurring via the concerted metalation/deprotonation pathways A (outer-sphere) and B (inner-sphere). For the prereaction complex, we find that weak coordination of the MPAA ligand to Pd(II) is affected by (a) the strong electron-withdrawing ability of the PG, (b) longer ...