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 products were formed via
route A2′ and cleavage of the P–O bond. The
P–S bonds were accompanied by the epimerization of the starting
materials, triggered by the alkylthio anion, via route C. The epimerization
can be suppressed by the use of a poorly soluble magnesium alkylthiolate,
and the P-retained compounds will be formed as the major products
via route B3 and BPR of the intermediates.