Mechanistic and Computational Study of a Palladacycle-Catalyzed Decomposition of a Series of Neutral Phosphorothioate Triesters in Methanol

The methanolytic cleavage of a series of <i>O</i>,<i>O-</i>dimethyl <i>O-</i>aryl phosphorothioates (<b>1a</b>−<b>g</b>) catalyzed by a <i>C</i>,<i>N</i>-palladacycle, (2-[<i>N</i>,<i>N</i>-dimethylamino(methyl)phenyl]-C<sup>1</sup>,N)(pyridine) palladium(II) triflate (<b>3</b>), at 25 °C and <sub>s</sub><sup>s</sup>pH 11.7 in methanol is reported, along with data for the methanolytic cleavage of <b>1a</b>−<b>g</b>. The methoxide reaction gives a linear log <i>k</i><sub>2</sub><sup>−OMe</sup> vs <sub>s</sub><sup>s</sup>p<i>K</i><sub>a</sub> (phenol leaving group) Brønsted plot having a gradient of β<sub>lg</sub> = −0.47 ± 0.03, suggesting about 34% cleavage of the P−OAr bond in the transition state. On the other hand, the <b>3</b>-catalyzed cleavage of <b>1</b> gives a Brønsted plot with a downward break at <sub>s</sub><sup>s</sup>p<i>K</i><sub>a</sub> (phenol) ∼ 13, signifying a change in the rate-limiting step in the catalyzed reaction, with the two wings having β<sub>lg</sub> values of 0.0 ± 0.03 and −1.93 ± 0.06. The rate-limiting step for good substrates with low leaving group <sub>s</sub><sup>s</sup>p<i>K</i><sub>a</sub> values is proposed to be substrate/pyridine exchange on the palladacycle, while for substrates with poor leaving groups, the rate-limiting step is a chemical one with extensive cleavage of the P−OAr bond. DFT calculations support this process and also identify two intermediates, namely, one where substrate/pyridine interchange has occurred to give the palladacycle coordinated to substrate through the SP linkage and to methoxide (<b>6</b>) and another where intramolecular methoxide attack has occurred on the PS unit to give a five-coordinate phosphorane (<b>7</b>) doubly coordinated to Pd via the S<sup>−</sup> and through a bridging methoxide linked to P and Pd. Attempts to identify the existence of the phosphorane by <sup>31</sup>P NMR in a <i>d</i><sub>4</sub>-methanol solution containing 10 mM each of <b>3</b>, trimethyl phosphorothioate (a very slow cleaving substrate), and methoxide proved unsuccessful, instead showing that the phosphorothioate was slowly converted to trimethyl phosphate, with the palladacycle decomposing to Pd<sup>0</sup> and free pyridine. These results provide the first reported example where a palladacycle-promoted solvolysis reaction exhibits a break in the Brønsted plot signifying at least one intermediate, while the DFT calculations provide further insight into a more complex mechanism involving two intermediates.