Copper-catalyzed intramolecular alkene carboetherification: synthesis of fused-ring and bridged-ring tetrahydrofurans

J Am Chem Soc. 2012 Jul 25;134(29):12149-56. doi: 10.1021/ja3034075. Epub 2012 Jul 5.

Abstract

Fused-ring and bridged-ring tetrahydrofuran scaffolds are found in a number of natural products and biologically active compounds. A new copper-catalyzed intramolecular carboetherification of alkenes for the synthesis of bicyclic tetrahydrofurans is reported herein. The reaction involves Cu-catalyzed intramolecular addition of alcohols to unactivated alkenes and subsequent aryl C-H functionalization provides the C-C bond. Mechanistic studies indicate a primary carbon radical intermediate is involved and radical addition to the aryl ring is the likely C-C bond-forming mechanism. Preliminary catalytic enantioselective reactions are promising (up to 75% ee) and provide evidence that copper is involved in the alkene addition step, likely through a cis-oxycupration mechanism. Catalytic enantioselective alkene carboetherification reactions are rare and future development of this new method into a highly enantioselective process is promising. During the course of the mechanistic studies a protocol for alkene hydroetherification was also developed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkenes / chemical synthesis
  • Alkenes / chemistry*
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Catalysis
  • Copper / chemistry*
  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Furans / chemical synthesis*
  • Furans / chemistry

Substances

  • Alkenes
  • Bridged Bicyclo Compounds
  • Ethers
  • Furans
  • Copper