Synthesis of Nitrogen-Containing Heterocycles and Cyclopentenone Derivatives via Phosphine-Catalyzed Michael Addition/Intramolecular Wittig Reaction

The phosphine-catalyzed Michael addition/intramolecular Wittig reaction between dialkyl acetylenedicarboxylate and amino-carbaldehyde or amino ester derivatives has been developped. This reaction can be rendered catalytic in phosphine by the in situ chemoselective reduction of the phosphine oxide with silane. This methodology enables rapid access to a variety of nitrogen-containing heterocycles, which are present in numerous natural products and/or bioactive compounds. Either classical heating or microwave conditions give access to the desired products in good yields (15 examples, 60-99% yields). This catalytic methodology is further applicable to the synthesis of enantioenriched 1H-pyrrole derivatives, with the use of chiral phosphines. Finally, we successfully extended the reaction to the synthesis of a polysubstituted cyclopentenone, starting from butane-2,3-dione as substrate.