The Mechanism of RuO4-Mediated Oxidations of Ethers: Isotope Effects, Solvent Effects and Substituent Effects.

Abstract

The mechanism of the RuO4-mediated oxidation of ethers to esters has been investigated. Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate. No rearranged products were observed. On RuO4 oxidation of benzyl methyl ether and p-methoxybenzyl methyl ether in CCl4 with NaIO4 as stoichiometric oxidant, no chlorinated products were observed. A series of 4-substituted benzyl methyl ethers was oxidized with RuO4-NaIO4. A correlation of the rate of the reaction with Hammett sigma-values gave a rho of - 1.7, indicating only a moderate charge separation in the transition state (TS). Benzyl methyl ether (1) was oxidized in a series of acetone-water mixtures. From these experiments, a Grunwald-Winstein m-value of 0.11 was obtained, indicating a non-polar TS for the reaction. PhCHDOCH(3) (2) and PhCD(2)OCH(3) (3) were oxidized and two deuterium isotope effects, one of 6.1 +/- 0.4 and another of 1.3 +/- 0.1 were obtained. If one assumes a one-step reaction mechanism, the value of 1.3 would be a large alpha-secondary isotope effect, indicating a change in the hybridization of the benzylic carbon during the reaction. alpha-Methylbenzyl methyl ether (4) was oxidized at a seventh of the rate of 1, despite the fact that 4 would have given a more stable carbocation than 1. These conflicting pieces of evidence are difficult to rationalise with a hydride or hydrogen abstraction mechanism. Instead it is proposed that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO4 followed by a slow concerted step to give the product.