Investigation of the Stereochemical Mechanism of the Nucleophilic Substitution Reaction at Pentacoordinate Phosphorus of Spirophosphorane.

The stereochemical mechanism of the nucleophilic substitution reaction at pentacoordinate phosphorus (P-V) atom is rarely studied. Here, we report the Atherton-Todd-type reaction of pentacoordinate hydrospirophosphorane with phenolic compounds in detail. The stereochemical mechanism of nucleophilic substitution at P-V atom was proposed by P NMR tracing experiment, X-ray diffraction analysis, and density functional theory calculations. The first step of the Atherton-Todd-type reaction is the formation of halogenated spirophosphorane intermediate with retention of configuration at phosphorus definitely. The second step is a nucleophilic substitution reaction at P-V atom of halogenated spirophosphorane. When using CCl as a halogenating agent, the reaction of chlorinated spirophosphorane proceeds via S2(P-V) mechanism, and the backside attack of P-Cl bond is the main pathway. For chlorinated spirophosphorane with Δ configuration, the completely P-inverted product is normally obtained. As for chlorinated spirophosphorane with Λ configuration, which has larger steric hindrance behind P-Cl bond, the proportion of P-retained products apparently increases and a pair of diastereoisomers is acquired. Furthermore, if CBr is used as a halogenating agent, the nucleophilic substitution reaction of brominated spirophosphorane may go through a S1(P-V) mechanism to afford a pair of diastereoisomers.