New Chiral Bifunctional Iminophosphorane Squaramide Organocatalysts: Synthesis and Application in the Enantioselective Michael Addition

Abstract The design and the synthesis of new enantiopure squaramide-based bifunctional iminophosphorane catalysts are reported. Starting from readily available starting materials, such as squarate and (S)-tert-leucinol, the synthetic approach involved the construction of a squaramide featuring an azide group, as precatalyst, which is easily stored, not sensible to moisture, and highly manageable. The chiral iminophosphorane organocatalysts (generated in situ by simple addition of a phosphine to the azide) were tested in the enantioselective Michael addition of α-nitro esters to enones and promoted the reaction in up to 90% yield and 60% e.e. The products are valuable precursors of α,α-disubstituted amino acids, important building blocks in the preparation of highly functionalized molecules. The synthesis of an α-methyl-substituted proline derivative was demonstrated.