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Synthesis of 2,6‐Disubstituted Piperidine‐Bearing α‐Amino Acid Side‐Chains
Author(s) -
Boeglin Damien,
Heitz Annie,
Martinez Jean,
Fehrentz JeanAlain
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300148
Subject(s) - chemistry , piperidine , stereocenter , hydrogenolysis , aldehyde , yield (engineering) , residue (chemistry) , stereochemistry , side chain , total synthesis , amino acid , organic chemistry , catalysis , enantioselective synthesis , polymer , biochemistry , materials science , metallurgy
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)