Nucleophilic reactions at acyclic phosphorus esters

Despite the biological importance of simple acyclic phosphate diesters, which include the nucleic acids, little detailed work had been done on their 

Stereochemical evidence for the mechanism of nucleophilic substitution at a tetracovalent phosphorus atom has been mainly forthcoming from the experiments of Michalski et a/.48-50 with esters containing thiophosphoryl centers. Until recently, the inaccessibility of suitable optically active phosphorus compounds precluded stereochemical investigations on the mechanisms of their hydrolysis. 

Several considerations recommended their employment (a) aromatic amines readily displace the more strongly basic aliphatic amines from phosphoramidic monoesters54 (b) the transition state for displacement would require the accommodation of phosphorus and the entering and leaving groups in a five- 

The hydrolysis in acid or base of five-membered cyclic esters of phosphoric acid proceed some 10 times faster than their acyclic analogs or the six- and seven-membered cyclic phosphates 55 56. Unlike that of dimethyl phosphate, the hydrolysis of hydrogen ethylene phosphate is accompanied by rapid oxygen exchange into the unreacted substrate57, viz- 

---