Copper-Catalyzed Skeletal Rearrangement of O-Propargyl Oximes: A Mechanistic Manifold

The Cu-mediated skeletal rearrangement of O-propargyl oximes features a mechanistic manifold that yields different compounds. Strategic modification of the substituent at the oxime moiety (R3) allows the selection of a preferred mechanistic route that leads to azete oxides/amidodienes (if R3 is an electron-poor/-rich aryl group) or to pyridine N-oxides (if R3 is an olefin). In the present work, we explore the mechanism that leads to each product. All the computed mechanisms have in common an initial stepwise 2,3-rearrangement that generates the key N-allenylnitrone intermediate the further reactivity of which will depend on the nature of the R3 substituent. Our calculations reveal the subtle details that govern the different behavior of this reaction with each of the aforementioned substituents and disclose a complex and multistep pathway to different aminodienes.