Complete 2,5-Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from a-Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres

Racemic alpha-iminocyanoacetates have been used as azomethine ylide precursors in the catalytic enantioselective [3+2]cycloaddition with alpha,beta-unsaturated aldehydes catalyzed by (S)-alpha,alpha-diphenylprolinol leading to the fully stereocontrolled formation of pyrrolidine cycloadducts with four stereocentres, one of them being a quaternary one. The reaction proceeded with excellent yields, endo-selectivities and enantioselectivities. Remarkably, complete 2,5-diastereoselection has also been achieved under the optimized reaction conditions, which has been explained in terms of the participation of intramolecular H-bonding interaction which contributes to stabilize one determined geometry for the in situ generated azomethine ylide.