Phthalides by rhodium-catalyzed ketone hydroacylation

J Am Chem Soc. 2009 Nov 4;131(43):15608-9. doi: 10.1021/ja907711a.

Abstract

Phthalides are biologically relevant five-membered lactones found in herbs, fruits, and vegetables. Herein we communicate the first atom-economical approach to phthalides by using enantioselective ketone hydroacylation. In the presence of Rh[(Duanphos)]X (X = NO(3), OTf, OMs), various 2-ketobenzaldehydes undergo intramolecular hydroacylation to produce phthalide products in good yields and 92-98% ee's. Our study highlights the key role counterions play in controlling both reactivity and enantioselectivity. A concise asymmetric total synthesis of the celery extract (S)-(-)-3-n-butylphthalide is also presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Catalysis
  • Phthalic Acids / chemistry*
  • Rhodium / chemistry*

Substances

  • Phthalic Acids
  • Rhodium