title: Carboxylic acids as a traceless activation group for conjugate additions: a three-step synthesis of (±)-pregabalin.
abstract: 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.
authors.affiliation: Merck Center for Catalysis at Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chu
authors.forename: Chisa
authors.initials: C
authors.lastname: Ohta
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zuo
authors.forename: David W C
authors.initials: DW
authors.lastname: MacMillan
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid