Carbonyl 1,2-transposition through triflate-mediated α-amination

Science. 2021 Nov 5;374(6568):734-740. doi: 10.1126/science.abl7854. Epub 2021 Nov 4.

Abstract

To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a simple one- or two-pot protocol that transposes a ketone to the vicinal carbon. This approach first converts the ketone to the corresponding alkenyl triflate, which can then undergo the palladium- and norbornene-catalyzed regioselective α-amination and ipso-hydrogenation enabled by a bifunctional hydrogen and nitrogen donor. The resulting “transposed enamine” intermediate can subsequently be hydrolyzed to produce the 1,2-carbonyl–migrated product. This method allows rapid access to unusual bioactive analogs through late-stage functionalization.

Publication types

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

MeSH terms

  • Amination
  • Carbon / chemistry*
  • Catalysis
  • Chemistry, Pharmaceutical
  • Hydrogen / chemistry
  • Hydrogenation
  • Ketones / chemistry*
  • Mesylates / chemistry*
  • Molecular Structure
  • Norbornanes / chemistry
  • Oxygen / chemistry*
  • Palladium / chemistry
  • Technology, Pharmaceutical

Substances

  • Ketones
  • Mesylates
  • Norbornanes
  • 2-norbornene
  • Palladium
  • Carbon
  • Hydrogen
  • trifluoromethanesulfonic acid
  • Oxygen