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

Abstract

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.

Keywords

• cascade
• imine
• Michael addition
• nitro-Mannich
• organocatalysis
• piperidine alkaloids