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 31 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 4 as a halogenating agent, the reaction of chlorinated spirophosphorane proceeds via S N 2(P–V) mechanism, and the backside attack of P–Cl bond is the main pathway. For chlorinated spirophosphorane with Δ P configuration, the completely P-inverted product is normally obtained. As for chlorinated spirophosphorane with Λ P 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 4 is used as a halogenating agent, the nucleophilic substitution reaction of brominated spirophosphorane may go through a S N 1(P–V) mechanism to afford a pair of diastereoisomers.