Ligand-Controlled Chemoselectivity in Manganese-Catalyzed Coupling of Benzyl Alcohol with Phosphorus Ylide: A Theoretical Study

The selective formation of C-C and C═C bonds is fundamentally important in pharmaceutical synthesis and materials science. Herein, the ligand-controlled chemoselectivity of the Mn-catalyzed coupling of benzyl alcohol (BnOH) with a phosphorus ylide for the C-C or C═C product was theoretically investigated through DFT and DLPNO-CCSD(T) calculations. For the PNP-supported catalyst <b>1A</b> ([Mn(CO)₂(N(C₂H₄P<i>ⁱ</i>Pr₂)₂)]), BnOH undergoes dehydrogenation via Mn-N cooperation (Δ<i>G</i>^≠ = 25.5 kcal/mol) to yield benzaldehyde and the Mn-hydride intermediate <b>4A</b>. Benzaldehyde subsequently reacts with the ylide via Wittig olefination to generate an E-alkene, which is selectively hydrogenated by <b>4A</b> (Δ<i>G</i>^≠ = 29.5 kcal/mol) to afford the C-C product. In contrast, the NNP-ligated catalyst favors C═C bond formation, as the corresponding Mn-hydride <b>4B</b> undergoes H₂ evolution (Δ<i>G</i>^≠ = 31.2 kcal/mol) rather than alkene hydrogenation (Δ<i>G</i>^≠ = 33.1 kcal/mol). This divergent reactivity originates from the lower hydride dissociation energy and greater steric hindrance of the NNP ligand, which collectively suppress alkene hydrogenation and promote H₂ release. Guided by these insights, catalyst <b>1A</b> was modified by replacing <i>ⁱ</i>Pr with bulkier <i>^t</i>Bu groups to construct <b>1C</b>, which shifts the chemoselectivity toward the C═C product exclusively. These findings emphasize the crucial role of ligand design in steering the chemoselectivity in base-metal-catalyzed transformations.