Dual Organocatalytic Ion-Pair Assemblies: A Highly Efficient Approach for the Enantioselective Oxa-Michael-Mannich Reaction of Salicylic Aldehydes with Cyclohexenones

A study was conducted to demonstrate a novel type of bifunctional catalyst generated by the self-assembly of pyrrolidines and readily available primary amino acids. It was demonstrated that the protonation of the aromatic nitrogen atom of pyrrolidines by amino acids spontaneously led to ion-pair assemblies. The self-assembled catalysts possessed dual activation centers and enabled the catalysis of the electrophilic and nucleophilic substrates similar to catalysis by enzymes. The simultaneous activation of cyclohex-2-enone and salicylic aldehyde by pyrrolidines and amino acids generated the transient ion pairs through iminiums and imines. The resultant assemblies ensured that the enantioselective domino oxa-Michael addition and intramolecular Mannich reaction proceeded to afford the corresponding products upon hydrolysis.