Tetramethylpiperidine N-Oxyl (TEMPO)-mediated Oxidative Functionalization of Alkoxyallenes

Allenes are versatile intermediates for the rapid construction of complex molecular frameworks, yet oxidative methods to install new C–C or C–X bonds across the three carbons of the allene often suffer from poor regioselectivity, competing overoxidation pathways, and limited generality. To address these challenges, we report a mild, efficient oxidative transformation of simple alkoxyallenes to multifunctional tetramethylpiperidine N-oxyl (TEMPO)–acrolein intermediates that function as masked trielectrophiles. These linchpins enable orthogonal diversification into heterocyclic scaffolds, including pharmaceutically relevant quinoxalines, imidazoles, oxazoles, and thiazoles. The synthetic utility of this platform is highlighted by a concise, metal-free synthesis of the natural product clathrodin from an alkoxyallene precursor. More broadly, TEMPO–acroleins provide a streamlined approach to complex molecular architectures from readily available allenes.