An asymmetric synthesis of (2S,5S)-5-substituted azepane-2-carboxylate derivatives

J Org Chem. 2011 Mar 18;76(6):1937-40. doi: 10.1021/jo102475s. Epub 2011 Jan 28.

Abstract

To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry*
  • Drug Discovery
  • Ketones / chemistry

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Carboxylic Acids
  • Ketones