Catalytic Enantioselective Intermolecular Desymmetrization of Azetidines

The first catalytic
asymmetric desymmetrization of azetidines is
disclosed. Despite the low propensity of azetidine ring opening and
challenging stereocontrol, smooth intermolecular reactions were realized
with excellent efficiency and enantioselectivity. These were enabled
by the suitable combination of catalyst, nucleophile, protective group,
and reaction conditions. The highly enantioenriched densely functionalized
products are versatile precursors to other useful chiral molecules.
Mechanistic studies, including DFT calculations, revealed that only
one catalyst molecule is involved in the key transition state, though
both reactants can be activated. Also, the Curtin–Hammett principle
dictates the reaction proceeds via amide nitrogen activation.