Programmable Functionalizations of Tetramethylpiperidine N-Oxyl (TEMPO)–Acrolein Linchpins Derived from Alkoxyallenes

Allenes are versatile precursors for constructing complex molecular frameworks, yet oxidative transformations to install C-C or C-heteroatom bonds across the C1-C3 framework rely on inconvenient reagents and yield overoxidized byproducts and unstable intermediates that limit downstream diversification. Herein, we report a general strategy to access multifunctional C(sp2)-TEMPO-acrolein linchpins from simple alkoxyallenes. These TEMPO-acrolein intermediates enable orthogonal transformations of all three carbons of the initial allene framework into heterocyclic scaffolds that include pharmaceutically relevant quinoxalines, imidazoles, oxazoles, and thiazoles. Finally, the utility of this new strategic paradigm is demonstrated through a concise, metal-free synthesis of the natural product clathrodin.