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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.

SUBMITTER: Chu L

PROVIDER: S-EPMC4132975 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Carboxylic acids as a traceless activation group for conjugate additions: a three-step synthesis of (±)-pregabalin.

Chu Lingling L Ohta Chisa C Zuo Zhiwei Z MacMillan David W C DW

Journal of the American Chemical Society 20140728 31

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 n ...[more]

PMID: 25032785

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