Hydrogen-Bonding Interactions in the Ley–Griffith Oxidation: Practical Considerations for the Synthetic Chemist

Abstract

The Ley–Griffith oxidation, which is catalyzed by tetra-n-propylammonium perruthenate (TPAP, nPr4N[RuO4]), is a popular method for not only controlled oxidation of primary alcohols to aldehydes, but also a host of other synthetically useful transformations. While the fundamental reaction mechanism has recently been elucidated, several key hydrogen-bonding interactions between the reagents were implicated but not investigated. Herein the prevalence of H-bonding between the co-oxidant N-methylmorpholine N-oxide (NMO), the alcohol substrate, water and the perruthenate catalyst is established. These observations help to rationalize the importance of drying the reagents and lead to several practical suggestions.