Elucidating the mechanism of the Ley-Griffith (TPAP) alcohol oxidation

The Ley-Griffith reaction is utilized extensively in the selective oxidation of alcohols to aldehydes or ketones. The central catalyst is commercially available tetra-n-propylammonium perruthenate (TPAP, n-Pr₄N[RuO₄]) which is used in combination with the co-oxidant N-methylmorpholine N-oxide (NMO). Although this reaction has been employed for more than 30 years, the mechanism remains unknown. Herein we report a comprehensive study of the oxidation of diphenylmethanol using the Ley-Griffith reagents to show that the rate determining step involves a single alcohol molecule, which is oxidised by a single perruthenate anion; NMO does not appear in rate law. A key finding of this study is that when pure n-Pr₄N[RuO₄] is employed in anhydrous solvent, alcohol oxidation initially proceeds very slowly. After this induction period, water produced by alcohol oxidation leads to partial formation of insoluble RuO₂, which dramatically accelerates catalysis via a heterogeneous process. This is particularly relevant in a synthetic context where catalyst degradation is usually problematic. In this case a small amount of n-Pr₄N[RuO₄] must decompose to RuO₂ to facilitate catalysis.