Intramolecular Hydrogen Bond Activation: Thiourea-Organocatalyzed Enantioselective 1,3-Dipolar Cycloaddition of Salicylaldehyde-Derived Azomethine Ylides with Nitroalkenes

An organocatalytic
strategy for the synthesis of tetrasubstituted
pyrrolidines with monoactivated azomethine ylides in high enantiomeric
excess and excellent exo/endo selectivity is presented. The key to
success is the intramolecular activation via hydrogen bonding through
an o-hydroxy group, which allows the dipolar cycloaddition
to take place in the presence of azomethine ylides bearing only one
activating group. The intramolecular hydrogen bond in the azomethine
ylide and the intermolecular hydrogen bond with the catalyst have
been demonstrated by DFT calculations and mechanistic proofs to be
crucial for the reaction to proceed.