Palladacycle-promoted solvolytic cleavage of O,O-dimethyl O-aryl phosphorothioates. Converting a phosphorane-like transition state to an observable intermediate

The mechanism of cleavage of a series of seven O,O-dimethyl O-aryl phosphorothioates (6a-g) promoted by a C,N-palladacycle, (2-N,N-dimethylamino(methyl)phenyl]-C(1),N)(pyridine) palladium(II) triflate (5:OTf) in methanol at 25 °C was investigated with the aim of identifying catalytically important intermediates. Complete (s)(s)pH/rate profiles (in methanol) were conducted for the cleavage of 6a-g in the presence of 0.08 mM 5. The log k(obs) for the catalyzed methanolysis of 6a increases linearly with (s)(s)pH with a plateau above the (s)(s)pK(a)(1) of 11.16 for formation of 5:(-)OCH3. The profiles for 6b-g are bell-shaped, depending on the apparent ionizations of two acidic groups, with the rate constant maximum of the bell and the (s)(s)pK(a)(1) values shifting to higher (s)(s)pH values as the (s)(s)pK(a)(HOAr) of the leaving group phenol increases. A Br?nsted plot of the log k(obs)(max) (the maximum rate constants for cleavage of 6a-g) vs (s)(s)pK(a)(HOAr) exhibits a downward break at ~ (s)(s)pK(a)(HOAr) 13, with the two wings having β(lg) values of 0.01 and -0.96. A model describing the kinetically important species involves a complex series of equilibria: 5:(HOCH(3)):pyr <=> 5:((-)OCH3):pyr + H(+) <=>(6) 5:((-)OCH3):6 + pyr <=> phosphorane 7 → product, where the rate limiting steps change from formation of 5:((-)OCH3):6 to formation of thiophosphorane 7 and then to product formation as the aryloxy leaving groups of 6 get progressively worse. Kinetic experiments indicate that the reaction of 5 with 6e, having a 4-chlorophenoxy leaving group, rapidly produces a transient intermediate, postulated to be the palladacycle-bound 5-coordinate thiophosphorane (7e) that exists long enough to obtain its UV/vis spectrum by stopped-flow spectrophotometry. Detailed analysis of the data sheds light on the origins of a previously reported anomalously large β(lg) of -1.93 for the descending wing of a Br?nsted plot (J. Am. Chem. Soc. 2010, 132, 16599). Finally, energetics analysis indicates that the binding of palladacycle to the transition state comprising attack of methoxide on 6e, MeO(-) + 6e](++), stabilizes the latter by 34.9 kcal/mol, converting that transition state into an observable intermediate.