The Brønsted Acid-Catalyzed, Enantioselective Aza-Diels-Alder Reaction for the Direct Synthesis of Chiral Piperidones.

We disclose herein the first enantioselective aza-Diels-Alder reaction of β-alkyl-substituted vinylketene silyl- O,O-acetals and imines furnishing a broad range of optically highly enriched 4-alkyl-substituted 2-piperidones. As a catalyst for this one-pot reaction we employed a chiral phosphoric acid which effects a vinylogous Mannich reaction directly followed by ring-closure to the lactam. Subsequent fully diastereoselective transformations including hydrogenation, enolate alkylation, and lactam alkylation/reduction processes converted the cycloadducts into various highly substituted piperidines of great utility for the synthesis of natural products and medicinally active compounds. [ABSTRACT FROM AUTHOR]