Enantioselective synthesis of trans-4-methylpipecolic acid

J Org Chem. 2007 Sep 28;72(20):7688-92. doi: 10.1021/jo071220z. Epub 2007 Sep 6.

Abstract

An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylamine / analogs & derivatives
  • Cyclization
  • Epoxy Compounds / chemistry
  • Pipecolic Acids / chemical synthesis*
  • Pipecolic Acids / chemistry
  • Stereoisomerism

Substances

  • Epoxy Compounds
  • Pipecolic Acids
  • Allylamine