Theoretical Study of a Derivative of Chlorophosphine with Aliphatic and Aromatic Grignard Reagents: SN2@P or the Novel SN2@Cl Followed by SN2@C?

The proposed S_N2 reactions of a hindered organophosphorus reactant with aliphatic and aromatic nucleophiles [Ye et al., Org. Lett. 19, 5384–5387 (2017)] were studied theoretically in order to explain the observed stereochemistry of the products. Our computations indicate that the reaction with the aliphatic nucleophile occurs through a backside S_N2@P pathway while the reaction with the aromatic nucleophile proceeds through a novel S_N2@Cl mechanism, followed by a frontside S_N2@C mechanism. To the best of our knowledge, this is the first time that a S_N2@Cl mechanism is reported. We also found that on reducing the bulkiness of substituents around the phosphorus atom, the backside S_N2@P mechanism is preferred. The conclusions made from investigating the steric effect should help experimentalists to decide for the organophosphorus reactant to achieve the products of desired stereochemistry.