Base-controlled diastereodivergent synthesis of (R)- and (S)-2-substituted-4-alkylidenepiperidines by the Wadsworth-Emmons reaction

J Org Chem. 2007 Feb 2;72(3):1005-8. doi: 10.1021/jo062075c.

Abstract

Significant base and reaction time effects have been observed in the Wadsworth-Emmons reaction between a chiral 2-substituted-4-oxopiperidine and phosphonates. In the reactions carried out using a large excess of DBU as the base and prolonged reaction times, the initially formed 2R products epimerized into thermodynamically more stable products through a retro-conjugate/conjugate addition sequence and 2-substituted-4-alkylidenepiperidines of 2S configuration were selectively synthesized. In contrast, when the reaction was carried out using LDA as the base, epimerization did not occur and 2-substituted-4-alkylidenepiperidines of 2R configuration were obtained with excellent yields.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkadienes / chemical synthesis*
  • Ligands
  • Models, Chemical
  • Organophosphonates / chemistry*
  • Piperidines / chemical synthesis*
  • Stereoisomerism
  • Thermodynamics

Substances

  • Alkadienes
  • Ligands
  • Organophosphonates
  • Piperidines