The halo-Nazarov cyclization with oxygen-containing systems has been studied extensively within our group. The nitrogen variant of this reaction, however, has not been reported until now. In this work, we explore a halide-trapped, alkynyl aza-Prins approach to access 3-substituted isoindolones capable of undergoing an unprecedented, triflic anhydride induced, amide activation/oxidation sequence. Upon oxidation, the resulting pentadienyl cation can undergo a 4π-electrocyclization, leading to the formation of spirocyclic isoindolones in good to excellent yields. Overall, this method allows for the efficient formation of two new rings, two new carbon-carbon bonds, an aza-tertiary stereocenter, and a vinyl halide functional handle. The methodology proved to be robust in the presence of electron-rich or electron-deficient substrates, and easily scalable without negative impacts on yield.

Synthesis of spirocyclic isoindolones using an alkynyl aza-Prins/oxidative halo-Nazarov cyclization sequence

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