Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl Compounds: Stereochemistry, Mechanism, and Applications

Nucleophilic substitutions at P centers are of high importance in biological processes and asymmetric synthesis. However, detailed studies on this topic are rare. P-Stereogenic compounds containing P–Cl, P–O, and P–S bonds were diastereoselectively prepared and then used to study the substitution of Cl, O, and S at phosphorus centers with organometallic reagents. It was proposed that with alkynyl metallic reagents an SN2-like mechanism (route A1) and a Berry pseudorotation (BPR) of pentacoordinated phosphorus intermediates (route B1) were involved and afforded P-inverted and P-retained products, respectively. The P-inverted conversion of a P–Cl functionality to a P–C functionality can be controlled by either the temperature or the order of addition of the starting materials. The introduction of a P–Cl bond using an alkyl metallic reagent proceeded through routes A2 and A2′. At higher temperatures, P-inverted products were predominantly afforded via SN2-like route A2. At lower temperatures, bis-substituted...