Study On The Atherton-Todd-type Reactions And Mechanisms Of Chiral Bisamino Hydrospirophosphoranes With Phenols

Pentacoordinate phosphorus compounds plays an important role in life system. For example, pentacoordinated phosphorus compounds was confirmed as potential transition states or intermediates in the phosphoryl transfer process and in the self-assembly reactions of N-phosphoamine acids into peptide, also in the biologically relevant phosphorus compounds such as RNA、DNA and c-AMP hydrolysis process. Hydrospirophosphorane (HSP) is a special type of pentacoordinate phosphorus compounds containing P-H bond, which is quite active to be a precursor for organic synthesis. At the same time the hydrospirophosphorane mostly have phosphorus chiral center, so there may exist change in configuration before and after the reaction. Houalla and Liu groups have studied the Atherton-Todd-type reaction of the fused heterocyclic hydridophosphorane and Masaaki Nakamoto has studied the reactions of the bicyclic hydridophosphorane containing martin ligands. However, up to now, there is a little progress in the Atherton-Todd-type reaction of hydrospirophosphoranes involving bisamino acid. Therefore, we use the bisamino hydrospirophosphorane as the model to study their Atherton-Todd-type reaction with phenol and the reaction mechanism in this paper.Firstly, hydrospirophosphoranes was synthesized from L-amino acids, then they were separated by silica gel column chromatography obtaining eight isomer. The Atherton-Todd-type reaction of pentacoordinate hydrospirophosphoranes with phenols was first investigated. A series of new types of phenoxy spirophosphoranes were synthesized, and their structures were confirmed by NMR、XRD、IR、MS. We have explored the impact of temperature and the acid binding agent’s basicity to the Atherton-Todd-type reaction. We successfully applied the carbon tetrabromide to Atherton-Todd-type reactions and studied its influence on the reaction result and the reaction rate. The important role of phase transfer catalyst on the Atherton-Todd reaction was found, and the result showed that it could accelerate the reaction and provide a good reaction conditions and methods under the conditions of containing aqueous solvent or nucleophile. It was found that the pentacoordinate hydrospirophosphoranes and part of the product existed Berry pseudorotation phenomenon under alkaline conditions, and the influence of temperature、solvent、 alkaline on Berry pseudorotation were investigated.Experiments have demonstrated that the Atherton-Todd-type reaction results between the same configuration of hydrospirophosphoranes and different substituted phenols are different, and the reaction results of the different configurations of hydrospirophosphoranes with the same phenols are also different. After numbers of experiments on tracing the reaction by31PNMR, an intermediate was found. Therefore, a possible reaction mechanism was presumed for this reaction according to the above results, and it was verified through various experiments. The exact Atherton-Todd-type reaction mechanism between bicyclic hydrospirophosphoranes and phenols was proposed as follows:The reaction first proceeded via the formation of chlorinated spirophosphorane intermediate with retention of the configuration at phosphorus, then the reaction between nucleophiles (phenols) and the intermediates take place through a hexacoordinated phosphorus transition state, which is confirmed to be an SN2tpye reaction. When the nucleophiles (phenols) attacked the phosphorus chiral center from the P-Cl bond backside, the main product with stereoinversion of the phosphorus chiral center was produced; when the nucleophiles attacking the phosphorus chiral center from the P-Cl bond front side, the minor products with stereoretention of the phosphorus chiral cente was formed. This study reveals the stereochemical characteristices of Atherton-Todd-type reaction between pentacoordinate hydrospirophosphoranes and phenols.