The Studies On The Stereochemical Mechanism Of The Nucleophilic Substitution Reaction Of Pentacoordinated Spirophosphorane

The pentacoordinated phosphorus compounds have received extensive attention,since they often participate in chemical reactions and life processes acting as common intermediate or transition state.However,due to the instability of pentacoordinated phosphorus compounds,further research on their properties is hindered.The pentacoordinated spirophosphane contains two rigid rings,which can stabilize pentacoordinated phosphorus compounds well,so they always are investigated as a model to carry out research on pentacoordinated phosphorus compounds.However,previous studies mainly focused on the theories and synthesis applications,and only a limited number of studies on the nucleophilic substitution have been reported so far,not to mention the investigation of the stereochemical mechanism.Hydrospirophosphane is a special type of spirophosphane,which contains P-H bonds that can take place a variety of reactions,so it is often used as the synthesis precursor of pentacoordinated spirophosphane.The bisaminoacyl hydrospirophosphane(AA-HSP)synthesized from amino acids by our research group contains three chiral centers and its chemical properties are relatively stable,so it can be used as an ideal model to study the stereochemical reaction mechanism of pentacoordinated phosphorus compounds.In this paper,a series of new pentacoordinated spirophosphoranes containing P-S bonds were synthesized by Atherton-Todd-type reactions.After that,the stereochemical mechanism of nucleophilic substitution of pentacoordinated spirophosphoranes was proposed by analyzing the effects of different reaction conditions on the stereochemical results.The DFT theoretical calculations were further used to verifiy the reaction mechanism proposed,and the results would help the following study of pentacoordinated phosphorus compounds.Firstly,AA-HSPs synthesized from different amino acids reactd with thiophenol compounds by Atherton-Todd-type reaction and a series of new spirophosphoranes were obtained.The reaction enriched the types of nucleophilic substitution reactions of AA-HSP,and contributed to the subsequent study of the nucleophilic substitution mechanism.Furthermore,the new spirophosphoranes containing P-S bond provided a new research substrate for the developement NMR method to determine the relative configuration of spirophosphane compounds.All the new products were characterized by NMR,HR-MS spectra.Secondly,the stereochemistry mechanism of the nucleophilic substitution reactions of pentacoordinated spirophosphorane was studied by control experiments.The effects of different configurations,different R groups of AA-HSP,different sterically hindered nucleophiles,and different leaving groups on the stereochemistry results were investigated.Subsequently,the stereochemical mechanism was proposed with the help of kinetics experiments and NMR tracking experiments.When CCl4 is used as a halogenating reagent,the first step of the reaction generates chlorospirophosphorane intermediate that maintains the phosphorus configuration,and then the intermediate reacts with nucleophile according to the SN2 mechanism.When the steric hindrance behind chlorospirophosphorane is small,nucleophile will attack from the back of P-Cl bond to generate product with the inverted configuration.In addition to the attack from back,a small amount of frontal attack of the P-Cl bond by nucleophile will occur when the steric hindrance behind the chlorospirophosphorane is large.Then,a pair of diastereomers is generated,and the product with the inverted configuration is still the majority.When CBr4 is used as a halogenating agent,the reaction of bromospirophosphorane tends to proceed according to the SNI mechanism,generating a pair of diastereomers in similar proportions.Finally,the proposed mechanism was verified by DFT calculations.The calculated results were in good agreement with the experimental phenomenon,which further illustrated the rationality of the proposed reaction mechanism.Furthermore,according to the calculation results,the reason for the different stereochemical results deriving from the same configuration with different R groups was inferred.And the influence of the hydrogen bond between the phenoxy anion and the N-H bond of spirophosphorane on the stereochemical results of the reaction was also excluded.The proposed stereochemical mechanism of nucleophilic substitution reaction of spirophosphorane will provide a theoretical basis for the subsequent synthesis of pentacoordinated spirophosphoranes in pure configuration,and also help to further understand the reaction characteristics of pentacoordinated phosphorus compounds.Furthermore,the results contribute to better exploration of the properties of pentacoordinated phosphorus compounds in the life process and chemical reactions.