Organocatalytic Asymmetric Inverse-Electron-Demand 1,3-Dipolar Cycloaddition of <i>N</i>,<i>N</i>′‑Cyclic Azomethine Imines

The first organocatalytic asymmetric inverse-electron-demand 1,3-dipolar cycloaddition (IED 1,3-DC) of N,N′-cyclic azomethine imines has been established in the presence of chiral phosphoric acid. This approach assembles N,N′-cyclic azomethine imines and o-hydroxystyrenes into chiral N,N-bicyclic pyrazolidin-3-one derivatives with the creation of two stereogenic centers, one of which is quaternary, in excellent diastereoselectivities and good enantioselectivities (up to >95:5 dr, 88:12 er). The investigation of the activation mode of the reaction revealed that the dual hydrogen-bonding interaction between the two substrates and the catalyst together with the conjugative effect initiated by the o-hydroxyl group played a crucial role in the designed IED 1,3-DC. This study will not only greatly enrich the underdeveloped research potential of catalytic asymmetric IED 1,3-DCs but will also facilitate the design of other enantioselective IED 1,3-DCs based on different activation modes.