Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Main Authors: Pavol Jakubec, Dane M. Cockfield, Madeleine Helliwell, James Raftery, Darren J. Dixon
• Format: Article
• Language: English
• Published: Beilstein-Institut 2012-04-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: cascade; imine; Michael addition; nitro-Mannich; organocatalysis; piperidine alkaloids
• Online Access: https://doi.org/10.3762/bjoc.8.64
• ISSN: 1860-5397

A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of substituted piperidines.