[en] Highlights: • The biosynthesis of R-phenylacetyl carbinol (R-PAC) is addressed theoretically for first time. • The protonation states of the N1′ and N4′ atoms of the HEThDP^- intermediate during the reaction are determined. • The reaction occurs via a synchronous concerted mechanism. • The activation free energies are 16.2 and 13.3 kcal/mol, in gas phase and solution, respectively. • The reaction is slightly exergonic, ΔG⁰ = −5.6 and −4.0 kcal/mol, for gas phase and solution, respectively. The reaction pathway leading to R-phenylacetyl carbinol within the quantum chemical cluster approach is addressed by means of density functional theory (DFT) calculations. The study includes calculation of Fukui functions, activation free energies, and potential energy surface scans, both in gas and solution phase. The protonation states of the nitrogen atoms of the pyrimidine moiety are determined. The reaction appears to be slightly exergonic (ΔG⁰ = −5.6 and −4.0 kcal/mol for gas and solution phase, respectively) following a concerted synchronous mechanism having activation free energy barriers of 16.2 and 13.3 kcal/mol, in gas phase and solution phase, respectively.