Transition State for Phospho Transfer

In nonenzymic substitution reactions of phosphoric esters and anhydrides, it is generally recognized that a diversity of mechanisms is allowed and that the 

Structure of the substrate and the reaction conditions determine the transition state for reaction with a particular nucleophile 104, 105). The extreme cases are generally described as the dissociative and associative substitution mechanisms. The fully dissociative mechanism entails the formation of monomeric metaphosphate monoanion as a discrete intermediate and was first formulated by F. H. Westheimer, who pioneered the physical organic chemistry of the hydrolysis of phosphate esters 106, 107). This mechanism is depicted in Eq. (40) and is possible only for phosphomonoesters with good leaving groups, examples of which are shown. 

The physical organic chemistry of the solvolysis of phosphomonoesters indicates that the reaction either involves an extended transition state with little bonding to POs in a concerted displacement of the leaving group, as illustrated. 

Phosphodiesters and phosphotriesters cannot undergo substitution reactions by dissociative mechanisms. Thus, the dibenzyl phosphate monoanion is much less reactive in hydrolysis than the benzyl phosphate monoanion (107). 

The reason for the low reactivity of dibenzyl phosphate is that it cannot expel benzyl alcohol to form metaphosphate. Therefore, the solvolysis must proceed by nucleophilic attack of hydroxide on the dibenzyl phosphate monoanion or attack of water on the neutral, acidic dibenzylphosphoric acid. 

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