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

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.

SUBMITTER: Trost BM

PROVIDER: S-EPMC5044515 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives <i>via</i> sequential palladium and copper catalysis.

Trost Barry M BM Masters James T JT Taft Benjamin R BR Lumb Jean-Philip JP

Chemical science 20160610 9

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 thi ...[more]

PMID: 27746892

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