Derivatized aliphatic amines represent a common and important class of chemical building blocks prevalent in the pharmaceutical, agrochemical and material industry. As a result, approaches to directly install functionality on simple and unbiased amine precursors remain of paramount importance. While functionalizing alpha to the nitrogen has been well-studied and numerous methods exist, achieving remote amine functionalization remains largely underdeveloped. Consequently, we reasoned that a direct and protecting group free oxygenation of aliphatic amines (to arrive at keto-amine products) would provide an ideal means for introducing diverse functionality. Through the use of high throughput experimentation (HTE) a photochemical oxidation was identified that relied upon hydrogen peroxide (or oxygen) as the oxidant in combination with a non-precious metal photocatalyst. These conditions were shown to selectively oxidize a series of diverse aliphatic amine starting materials to their remotely oxidized analogs and was amenable to scale-up in flow.
















Danielle Schultz (Merck - Enabling Technologies Group)