Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Nature. 2011 Mar 24;471(7339):461-6. doi: 10.1038/nature09957.

Abstract

Alkenes are found in many biologically active molecules, and there are a large number of chemical transformations in which alkenes act as the reactants or products (or both) of the reaction. Many alkenes exist as either the E or the higher-energy Z stereoisomer. Catalytic procedures for the stereoselective formation of alkenes are valuable, yet methods enabling the synthesis of 1,2-disubstituted Z alkenes are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and of allylic amides, used until now only in E-selective processes. The corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. These transformations, promoted by catalysts that contain the highly abundant and inexpensive metal molybdenum, are amenable to gram-scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. The utility of this method is demonstrated by its use in syntheses of an anti-oxidant plasmalogen phospholipid, found in electrically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant KRN7000.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / chemistry
  • Alkenes / chemical synthesis*
  • Alkenes / chemistry*
  • Amides / chemical synthesis
  • Amides / chemistry
  • Antioxidants / metabolism
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry*
  • Catalysis
  • Ethers / chemistry
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / chemistry
  • Molecular Structure
  • Molybdenum / chemistry
  • Plasmalogens / chemical synthesis
  • Plasmalogens / chemistry
  • Stereoisomerism

Substances

  • Adjuvants, Immunologic
  • Alkenes
  • Amides
  • Antioxidants
  • Biological Products
  • Ethers
  • Galactosylceramides
  • Plasmalogens
  • Molybdenum
  • KRN 7000