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

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. Further exploration of the Ley–Griffith (TPAP) oxidation has unveiled a better understanding of the role N‐methylmorpholine N‐oxide (NMO) plays, not just as a co‐oxidant, but also a hydrogen bonding partner to the alcohol substrate and water. These additional attributes impact reaction performance, with important implications for the practicing synthetic chemist. [ABSTRACT FROM AUTHOR]