Highly enantioselective syntheses of functionalized alpha-methylene-gamma-butyrolactones via Rh(I)-catalyzed intramolecular Alder ene reaction: application to formal synthesis of (+)-pilocarpine

J Am Chem Soc. 2002 Jul 17;124(28):8198-9. doi: 10.1021/ja020052j.

Abstract

A highly enantioselective Rh(I)-catalyzed intramolecular Alder ene reaction has been developed. The desired products, 3-vinyl, vinyl acetate, and vinyl ether-substitued alpha-methylene-gamma-butyrolactones were formed in high yields. Aldehydes were produced with the formation of gamma-lactones when alcohols were substituted at allylic position in the substrates. All reactions with listed substrates proceeded in over 99% ee. A formal synthesis of (+)-pilocarpine is an excellent example to demonstrate the synthetic utility of this methodology.

Publication types

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

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis*
  • 4-Butyrolactone / chemistry
  • Alkynes / chemistry
  • Catalysis
  • Naphthalenes / chemistry
  • Organometallic Compounds / chemistry
  • Pilocarpine / chemical synthesis*
  • Rhodium / chemistry*
  • Stereoisomerism

Substances

  • Alkynes
  • BINAP, 2-naphthol
  • Naphthalenes
  • Organometallic Compounds
  • Pilocarpine
  • alpha-methylene gamma-butyrolactone
  • Rhodium
  • 4-Butyrolactone