A multi-level multi-layer QM/QM method, the relativistic pseudopotential correlation-consistent composite approach within an ONIOM framework (rp-ccCA-ONIOM), was applied to study the oxidative addition of the CαCβ bond in an archetypal arylglycerol β-aryl ether (β-O-4 linkage) substructure of lignin to Ni, Cu, Pd and Pt transition metal atoms. The chemically active high-level layer is treated using the relativistic pseudopotential correlation-consistent composite approach (rp-ccCA), an efficient methodology designed to reproduce an accuracy that would be obtained using the more computationally demanding CCSD(T)/aug-cc-pCV∞Z-PP, albeit at a significantly reduced computational cost, while the low-level layer is computed using B3LYP/cc-pVTZ. The thermodynamic and kinetic feasibilities of the model reactions are reported in terms of enthalpies of reactions at 298 K (ΔH°298) and activation energies (ΔH-act). The results obtained from the rp-ccCA:B3LYP hybrid method are compared to the corresponding values using CCSD(T) and several density functionals including B3LYP, M06, M06 L, B2PLYP, mPWPLYP and B2GP-PLYP. The energetics of the oxidative addition of CC bond in ethane to Ni, Cu, Pd and Pt atoms are also reported to demonstrate that the rp-ccCA method effectively reproduces the accuracy of the CCSD(T)/aug-cc-pCV∞Z method. Our results show that in the catalytic activation of the CαCβ bond of β-O-4, the use of platinum metal catalysts will lead to the most thermodynamically favored reaction with the lowest activation barrier.