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Issue 9, 2016
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Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis

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Abstract

We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regio- and enantioselective copper-catalyzed conjugate reduction. The process exhibits a high functional group tolerance, and this enables the synthesis of a broad range of chiral products from simple, readily available alkyne precursors. The utility of the method is demonstrated through the elaboration of the chiral β-alkynyl products into a variety of different molecular scaffolds. Its value in complex molecule synthesis is further validated through a concise, enantioselective synthesis of AMG 837, a potent GPR40 receptor agonist.

Graphical abstract: Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis

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Publication details

The article was received on 19 Apr 2016, accepted on 09 Jun 2016 and first published on 10 Jun 2016


Article type: Edge Article
DOI: 10.1039/C6SC01724J
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Citation: Chem. Sci., 2016,7, 6217-6231
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    Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis

    B. M. Trost, J. T. Masters, B. R. Taft and J. Lumb, Chem. Sci., 2016, 7, 6217
    DOI: 10.1039/C6SC01724J

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