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. 2014 Aug 6;136(31):10886-9.
doi: 10.1021/ja505964r. Epub 2014 Jul 28.

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

Lingling Chu  1 , Chisa Ohta, Zhiwei Zuo, David W C MacMillan
Affiliations

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

Lingling Chu et al. J Am Chem Soc. .

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.

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Figures

Scheme 1
Scheme 1. Proposed Mechanism for Decarboxylative Alkylation
See this image and copyright information in PMC

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