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

Abstract

<p>The proposed S<sub>N</sub>2 reactions of a hindered organophosphorus reactant with aliphatic and aromatic nucleophiles [Ye <i>et al.</i>, Org. Lett. <b>19</b>, 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<sub>N</sub>2@P pathway while the reaction with the aromatic nucleophile proceeds through a novel S<sub>N</sub>2@Cl mechanism, followed by a frontside S<sub>N</sub>2@C mechanism. To the best of our knowledge, this is the first time that a S<sub>N</sub>2@Cl mechanism is reported. We also found that on reducing the bulkiness of substituents around the phosphorus atom, the backside S<sub>N</sub>2@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.</p>