Organocatalytic Asymmetric Robinson Annulation of α,β-Unsaturated Aldehydes: Applications to the Total Synthesis of (+)-Palitantin

The highly enantioselective organocatalytic Robinson annulation of α,β-unsaturated aldehydes was
achieved, catalyzed by l-proline and trialkylamines and providing the formal [4 + 2] cycloaddition adducts.
Additionally, in some examples in the catalysis with diarylpyrrolinol silyl ethers, the reactions afforded
the [4 + 2] adducts with high enantioselectivity (>99.5% ee). The structure of the adduct, obtained from
the reaction of 3-methylbut-2-enal and (E)-3-(2-nitrophenyl)acrylaldehyde, was confirmed by X-ray
analysis. The absolute configurations of some [4 + 2] cycloadducts were investigated, and the methodology
was applied in the synthesis of (+)-palitantin.