Asymmetric Nitrone Synthesis via Ligand-Enabled Copper-Catalyzed Cope-Type Hydroamination of Cyclopropene with Oxime

We report realization of the first
enantioselective Cope-type hydroamination
of oximes for asymmetric nitrone synthesis. The ligand promoted asymmetric
cyclopropene “hydronitronylation” process employs a
Cu-based catalytic system and readily available starting materials,
operates under mild conditions and displays broad scope and exceptionally
high enantio- and diastereocontrol. Preliminary mechanistic studies
corroborate a CuI-catalytic profile featuring an olefin metalla-retro-Cope aminocupration process as the key C–N
bond forming event. This conceptually novel reactivity enables the
first example of highly enantioselective catalytic nitrone formation
process and will likely spur further developments that may significantly
expedite chiral nitrone synthesis.