Phosphonothioate Hydrolysis by Molybdocene Dichlorides: Importance of Metal Interaction with the Sulfur of the Thiolate Leaving Group

The metallocene bis(cyclopentadienyl)molybdenum(IV) dichloride Cp2MoCl2 hydrolyzes O,S-diethyl phenylphosphonothioate (1) with only P-S scission to yield a phosphonate under mild aqueous conditions. In terms of degrading phosphonothioate neurotoxins, exclusive cleavage of the P-S linkage is preferred, for P-O scission yields another toxic phosphonothioate. Structure activity relationship studies were undertaken with various phosphonothioates to test the hypothesis for the exclusive P-S scission by Cp2Mo(aq). Kinetics data show that the rates of phosphonothioate hydrolysis correspond to the size of the alkanethiolate leaving group on treatment with Cp2MoCl2. This suggests that the exclusive P-S scission of 1 is due to the interaction between the thiophilic Cp2Mo with the sulfur site of the P-SR linkage.