Physical organic origin of ligand-controlled β/γ-regiodivergence in NiH-catalyzed hydroalkylation

Abstract

Ligand-controlled β/γ-regiodivergence in NiH-catalyzed hydroalkylation offers an attractive strategy for accessing structurally distinct azaarene products, but the physical origin of this selectivity reversal remains unclear. Herein, we reveal that β/γ-selectivity is not determined solely by the initial hydrometalation step, but by the subsequent competition between direct radical rebound and chain walking. DFT calculations, activation strain analysis, energy decomposition analysis, and interpretable descriptor analysis show that productive chain walking requires two ligand-dependent conditions: access to a singlet alkylnickel state and a feasible β-hydride elimination. Conventional N-donor ligands suppress both requirements and favor γ-selective radical rebound, whereas P-donor ligands enable spin-state access and lower the β-hydride elimination barrier, leading to β-selective migratory hydroalkylation. The sterically encumbered N-donor ligand L2 defines a boundary regime in which β-hydride elimination becomes competitive before full singlet-state preference is achieved. These findings establish a concise physical organic model for understanding ligand-controlled β/γ-regiodivergence in NiH chain-walking hydroalkylation. More broadly, the ODI_HOMO_1/NPA_Ni_H descriptor map provides a physically interpretable framework for guiding future ligand design and understanding regioselectivity trends in NiH-catalyzed migratory functionalization reactions.