Christopher I. Maxwell

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 O,O-dimethyl O-aryl phosphorothioates (1a−g) catalyzed by a C,N-palladacycle, (2-[N,N-dimethylamino(methyl)phenyl]-C1,N)(pyridine) palladium(II) triflate (3), at 25 °C and sspH 11.7 in methanol is reported, along with data for the methanolytic cleavage of 1a−g. The methoxide reaction gives a linear log k2−OMe vs sspKa (phenol leaving group) Brønsted plot having a gradient of βlg = −0.47 ± 0.03, suggesting about 34% cleavage of the P−OAr bond in the transition state. On the other hand, the 3-catalyzed cleavage of 1 gives a Brønsted plot with a downward break at sspKa (phenol) 13, signifying a change in the rate-limiting step in the catalyzed reaction, with the two wings having βlg values of 0.0 ± 0.03 and −1.93 ± 0.06. The rate-limiting step for good substrates with low leaving group sspKa 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 (6) and another where intramolecular methoxide attack has occurred on the P═S unit to give a five-coordinate phosphorane (7) doubly coordinated to Pd via the S− and through a bridging methoxide linked to P and Pd. Attempts to identify the existence of the phosphorane by 31P NMR in a d4-methanol solution containing 10 mM each of 3, 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 Pd0 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.

Solvent deuterium kinetic isotope effects for the methanolyses of neutral CO, PO and PS esters catalyzed by a triazacyclododecane : Zn2+-methoxide complex

The methanolyses of several organophosphate/phosphonate/phosphorothioate esters (O,O-diethyl O-(4-nitrophenyl) phosphate, paraoxon, ; O,O-diethyl S-(3,5-dichlorophenyl) phosphorothioate, ; O-ethyl O-(2-nitro-4-chlorophenyl) methylphosphonate, ; O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate, fenitrothion, ; O-ethyl S-(3,5-dichlorophenyl) methylphosphonothioate ) and a carboxylate ester (p-nitrophenyl acetate, ) catalyzed by methoxide and the Zn(2+)((-)OCH(3)) complex of 1,5,9-triazacyclododecane ( : Zn(2+)((-)OCH(3))) were studied in methanol and d(1)-methanol at 25 degrees C. In the case of the methoxide reactions inverse skies were observed for the series with values ranging from 2 to 1.1, except for where the k(D)/k(H) = 0.90 +/- 0.02. The inverse k(D)/k(H) values are consistent with a direct nucleophilic methoxide attack involving desolvation of the nucleophile with varying extents of resolvation of the TS. With the : Zn(2+)((-)OCH(3)) complex all the skie values are k(D)/k(H) = 1.0 +/- 0.1 except for where the value is 0.79 +/- 0.06. Arguments are presented that the fractionation factors associated with complex : Zn(2+)((-)OCH(3)) are indistinguishable from unity. The skies for all the complex-catalyzed methanolyses are interpreted as being consistent with an intramolecular nucleophilic attack of the Zn(2+)-coordinated methoxide within a pre-equilibrium metal : substrate complex.

Methanolysis of thioamide promoted by a simple palladacycle is accelerated by 10(8) over the methoxide-catalyzed reaction.

Palladacycle 1 catalyzes the methanolytic cleavage of N-methyl-N-(4-nitrophenyl)thiobenzamide (4) via a mechanism involving formation of a Pd-bound tetrahedral intermediate (TI). The rate constant for decomposition of the complex formed between 1, methoxide, and 4 is 9.3 s(-1) at 25 °C; this reaction produces methyl thiobenzoate and N-methyl-4-nitroaniline. The ratio of the second-order rate constant for the catalyzed reaction, given as k(cat)/K(d), relative to that of the methoxide-promoted reaction is 3 × 10(8), representing a very large catalysis of thioamide bond cleavage by a synthetic metal complex.