Organocatalytic Michael Addition of Nitro Esters to α,β-Unsaturated Aldehydes: Towards the Enantioselective Synthesis of trans-3-Substituted Proline Derivatives

A facile five-step strategy has been developed for the enantioselective synthesis of trans-3-substituted proline derivatives with high diasteroselectivity (dr>20:1) and enantioselectivity (up to 97% ee). The key step is the asymmetric organocatalytic Michael addition of nitro esters to a,beta-unsaturated aldehydes, which affords the chiral Michael adducts in high yields (up to 96%) and excellent enantioselectivity (up to 99% ee) by using diarylprolinol silyl ether as the organocatalyst.