The Investigation Of The Stereochemistry Of The Atherton-todd-type Reactions Of Bis(aminoacyl)spirophosphoranes Containing A Chiral Phosphorus Center With Phenols

As known as the control center of the physiological and biochemical reactions, phosphorus compounds occupy an important position in the life system. Morever, pentacoordinate phosphorus compounds have been confirmed as intermediates or transition-state species in numerous biological processes. Hydrospirophosphorane(HSP) containing P-H bond is a special type of pentacoordinate phosphorus compounds because of its reaction activity. A new type of hydrospirophosphoranes(AA-HSPs), which was synthesized from amino acids, appeared as an ideal pentacoordinate phosphorane model to study the stereochemistry of pentacoordinate phosphorus compounds owing to their stability in the air. In this paper, the yield of the synthesis of pentaccordinate bis(aminoacyl)spirophosphoranes(Leu-HSP, Ala-HSP) was improved, and two pairs of diastereoisomers was obtained. Then they were separated by column chromatography, respectively. The Atherton-Todd-type reactions between Leu-HSP with pure configuration and phenols were investigated, separately. Moreover, the reactions of the Ala-HSP with phenols were also studied. The sterechemistry of the reaction of Leu-HSP and Ala-HSP with phenols was detected by the 31 P NMR. The structures of the new compounds were characterized by IR, NMR,HRMS and XRSD.And the Atherton-Todd-type reaction between Val-HSP, Ile-HSP and Phe-HSP with phenols had been studied. Therefore, the mechanism of the stereochemistry of the Atherton-Todd-type reaction of the AA-HSPs with phenols was verified from the point of the absolute configurations of phosphorus atoms of the AA-HSPs, the steric hindrance of the substituent groups of the AA-HSPs and the substituent groups around the phenolic hydroxy. First, the chlorinated spirophosphorane intermediate was obtained with the retention of the phosphorus configuration in the Atherton-Todd reaction condition. Then, the nucleophiles attacked the P-Cl bond and the reaction proceeded through a hexacoordinated phosphorus transition state before the corresponding products were gotten. The nucleophiles usually attacked the back face of the P-Cl bond, so the configurations of the final products were stereoinversion, which were the main products. The results showed that the stereochemistry of the reaction was directly affected by the steric hindrance of the substituent groups of the AA-HSPs and the phenolic hydroxy. So does the absolute configurations of phosphorus atoms of the AA-HSPs. The result was accordant to the theoretical calculation, which further validated the rationality of the mechanism. The mechanism reveals the stereochemistry of the Atherton-Todd-type reaction of the AA-HSPs with phenols. And it might step forward to the research of the stereochemistry of the pentaccordinate phosphosrus compounds.