Total synthesis of (-)-(α)-kainic acid via a diastereoselective intramolecular [3 + 2] cycloaddition reaction of an aryl cyclopropyl ketone with an alkyne

Org Lett. 2012 May 18;14(10):2540-3. doi: 10.1021/ol3008414. Epub 2012 May 3.

Abstract

An enantioselective synthesis of (-)-(α)-kainic acid in 15 steps with an overall yield of 24% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with complete diastereoselectivity via an unprecedented SmI2-catalyzed intramolecular [3 + 2] cycloaddition reaction of an aryl cyclopropyl ketone and an alkyne. Double bond isomerization was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(α)-kainic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Cycloaddition Reaction
  • Kainic Acid / chemical synthesis*
  • Kainic Acid / chemistry
  • Ketones / chemistry*
  • Molecular Structure
  • Pyrrolidines / chemistry
  • Stereoisomerism

Substances

  • Alkynes
  • Ketones
  • Pyrrolidines
  • pyrrolidine
  • Kainic Acid