Reactions of phosphate and phosphorothiolate diesters with nucleophiles: comparison of transition state structures

A series of methyl aryl phosphorothiolate esters (SP) were synthesized and their reactions with pyridine derivatives were compared to those for methyl aryl phosphate esters (OP). Results show that SP esters react with pyridine nucleophiles via a concerted S(N)2(P) mechanism. Brønsted analysis suggests that reactions of both SP and OP esters proceed via transition states with dissociative character. The overall similarity of the transition state structures supports the use of phosphorothiolates as substrate analogues to probe mechanisms of enzyme-catalyzed phosphoryl transfer reactions.