Synthesis of 2,6-Disubstituted Piperidine-Bearing α-Amino Acid Side-Chains

✍ Scribed by Damien Boeglin; Annie Heitz; Jean Martinez; Jean-Alain Fehrentz

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 166 KB
• Volume: 2003
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200300148

✦ Synopsis

Abstract

A straightforward synthesis of 2,6‐disubstituted piperidines bearing α‐amino acid side‐chains was developed. Synthesis was based on a Horner−Wadsworth−Emmons condensation of a β‐ketophosphonate derived from an α‐amino acid residue with a β‐homologated aldehyde of an N‐protected amino acid residue. The generated α‐β unsaturated ketones were then reduced, deprotected, and cyclized in a hydrogenation/hydrogenolysis one‐pot procedure to yield piperidine moieties. Introduction of a new conformational restriction in the obtained molecules allowed total assignment of the stereocenters by NMR experiments. This assignment allowed us to propose a mechanistic pathway during the cyclization process, explaining the loss of exocyclic carbon‐center configuration. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)