Nitrogen radical-triggered trifunctionalizing ipso-spirocyclization of unactivated alkenes with vinyl azides towards new spiroaminal frameworks

Abstract Radical-mediated spirocyclization is a powerful and efficient tool to forge complex spirocyclic frameworks. Radical-mediated non-dearomative double-cyclization of linear precursors for the concomitant construction of both rings is more challenging but highly attractive. Herein, we report the first example of non-dearomative trifunctionalizing ipso-spirocyclization of unactivated alkenes through photoredox-catalyzed, nitrogen radical-triggered cyclization-trapping-translocation-cyclization cascade, providing a single-step modular access to architecturally new and fascinating spiroaminal frameworks through simultaneous formation of one C−C bond and two geminal C−N bonds. The developed protocol utilizes not only internal or terminal olefinic oxime esters but also olefinic amides as nitrogen radical precursors, and features broad substrate scope, varied functional group compatibility, easy scalability, and potential for product derivatization and late-stage functionalization of biologically active molecule. Importantly, the mechanistic studies including DFT calculations indicate that such photocatalytic trifunctionalizing ipso-spirocyclization undergoes a radical relay cascade of intramolecular 5-exo-trig cyclization, intermolecular radical trapping, 1,5-hydrogen atom transfer, and sequential 5-endo-trig cyclization, which would open up a new reaction mode of alkenes.