Carboxylic Acids as A Traceless Activation Group for Conjugate Additions: A Three-Step Synthesis of (±)-Pregabalin

The direct application of carboxylic acids as a traceless activation group for radical Michael additions has been accomplished via visible light-mediated photoredox catalysis. Photon-induced oxidation of a broad series of carboxylic acids, including hydrocarbon-substituted, α-oxy, and α-amino acids, provides a versatile CO2-extrusion platform to generate Michael donors without the requirement for organometallic activation or propagation. A diverse array of Michael acceptors is amenable to this new conjugate addition strategy. An application of this technology to a three-step synthesis of the medicinal agent pregabalin (commercialized by Pfizer under the trade name Lyrica) is also presented.

• A
  Amgen
• P
  Pfizer
• NI
  National Institutes of Health
• NI
  National Institute of General Medical Sciences

  Award: R01 GM103558-03