The reaction for the formation of the xuxuarine Aα triterpene dimer in an aqueous medium was studied using the ONIOM/CPCM-X scheme at the ONIOM(M06-2X/6-31G(d,p):PM6) level of theory, along with the inclusion of one and two explicit water molecules. The results show that the geometry of the water molecules in the complex of reactants switches the mechanism from a one-step to a two-step hetero Diels–Alder (HDA) reaction. The reaction begins with a Michael addition assisted by water, which is the rate-limiting step. Then, nucleophilic addition–protonation involving nucleophilic attack at the positive carbon center of the carbonyl group takes place. The two-step mechanism has an activation free energy that is 4.7 kcal mol⁻¹ lower than the one-step mechanism, providing evidence of an alternative two-step water-assisted reaction for the biogenic origin of triterpene dimers.