Direct asymmetric amination of α-branched cyclic ketones catalyzed by a chiral phosphoric acid

J Am Chem Soc. 2015 Mar 11;137(9):3205-8. doi: 10.1021/jacs.5b00229. Epub 2015 Feb 26.

Abstract

Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantioselectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantioenriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (S)-ketamine, the more active enantiomer of this versatile pharmaceutical.

Publication types

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

MeSH terms

  • Amination
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Ketamine / chemical synthesis*
  • Ketones / chemical synthesis
  • Ketones / chemistry*
  • Phosphoric Acids / chemistry*
  • Stereoisomerism

Substances

  • Ketones
  • Phosphoric Acids
  • Ketamine
  • phosphoric acid