The Atherton-Todd Reaction And Reaction Mechanism Study Of Phenylalanine Hydrospirophosphorane And Phenols

Pentacoordinate phosphorus compounds are very important in biological chemistry.For example,the processes of hydrolyses of RNA,energy transfer of ATP or phosphoryl transfer reactions is through pentacoordinate phosphorus compounds as transition-state species or intermediates.Hydrospirophosphorane is a special type of pentacoordinate phosphorus compounds involving P-H bond,which is active enough to be precursors for organic synthesis.Liu or Houalla’s groups studied the Atherton-Todd reaction of the condensed bicyclic hydridophosphorane,and Masaaki Nakamoto’s group studied the Atherton-Todd reaction of the bicyclic hydridophosphorane with Matin ligands.However,until now,there is no research on the Atherton-Todd reaction of hydrospirophosphoranes involving bi-amino acid unit.Therefore,in this paper,we investigated the Atherton-Todd reaction and the reaction mechanism of bi-phenylalanine Hydrospirophosphorane and phenolsThe bi-amino acid Hydrospirophosphorane were a pair of diastereoisomer,so we optimized the separateing condition by their difference of solubility and obtained eight products in single configuration and in good yield.When we studied the Atherton-Todd reaction of bi-phenylalanine Hydrospirophosphorane in single configuration with p-cresol,it was found that a pair of products was obtained.First,we investigated the impact of alkalis,temperature,solvent and nitrogen atmosphere on the reaction of bi-phenylalanine Hydrospirophosphorane with p-cresol.Then we obtained23new spirophosphoranes from the reactions of bi-phenylalanine Hydrospirophosphorane with phenol-blocked.The structures of these new phosphorane compounds were identified by ESI-MS,NMR and IR spectrum.It was found that the products are a pair diastereoisomer by the chiral center of phosphorus and the relative ratio of these pair products were different for the different phenols.It was testified that the reaction went through the intermediate chlorophosphorane by31P-NMR tracing experiment and the ratio of the stereoisomers products was highly depended on the size and position of the substituent of phenols.Therefore,we presumed a possible reaction mechanism for this reaction from series of results.The phenol attracted the phosphorus atom in two ways:front attack and rear attack of chlorophosphorane,and rear attack was the electronically preferred direction.The size and position of the substituent of the phenols determined the attack direction of nucleophilic reagent to the chlorophosphorane,so the different ratios were observed.Then we designed a series of experiments to verify the possible reaction mechanism.At the same time the stereochemistry characteristics of the reaction were reasonably explained.In addition,we studied the fragmentation pathways of the23new phosphorane compounds by electrospray ionization multistage mass spectrometry(ESI-MSn).It was found that the size and position of the substituent of phenols have great influence to the fragmentation pathways of the new phosphorane compounds.The fragmentation pathways were summarized.At the same time the fragmentation pathways were speculated and estimated by the B3LYP/6-31+G(d,p)model of Density Fuctional Theory.The fragmentation pathways of these compouds may establish foundation for speculating or identifying the structure of related compouds by ESI-MS".