One-pot formation of piperidine- and pyrrolidine-substituted pyridinium salts via addition of 5-alkylaminopenta-2,4-dienals to N-acyliminium ions: application to the synthesis of (±)-nicotine and analogs

Org Lett. 2010 Nov 5;12(21):4760-3. doi: 10.1021/ol101783c.

Abstract

Addition of 5-alkylaminopenta-2,4-dienals onto N-acyliminium ions, generated in situ from α-hydroxycarbamates derived from pyrrolidine or piperidine, in the presence of zinc triflate, followed by dehydrative cyclization, allowed the formation of pyridinium salts substituted at their 3-position by a five- or six-membered nitrogen heterocycle. Subsequent N-dealkylation of the pyridinium moiety and deprotection of the secondary amine or reduction of the carbamate function led to (±)-nicotine and analogs.

MeSH terms

  • Acrylates / chemistry*
  • Alkylation
  • Amines / chemistry*
  • Imines / chemistry*
  • Ions / chemistry
  • Molecular Structure
  • Nicotine / analogs & derivatives
  • Nicotine / chemical synthesis*
  • Piperidines / chemistry*
  • Pyridinium Compounds / chemistry*
  • Pyrrolidines / chemistry*

Substances

  • Acrylates
  • Amines
  • Imines
  • Ions
  • Piperidines
  • Pyridinium Compounds
  • Pyrrolidines
  • piperidine
  • Nicotine
  • acrylic acid
  • pyrrolidine