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Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents

Yaowen Liu, Martin C. Dietl, Chunyu Han, Matthias Rudolph, Frank Röminger, Petra Krämer, A. Stephen K. Hashmi

2022Organic Letters23 citationsDOI

Abstract

Multisubstituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) with perfect atom-economy. The EBX reagents transfer both the carboxylate as well as the alkynyl entity. Overall, this cascade comprises the in situ generation of an alkynyl gold(III) species, a stereoselective C(sp)–C(sp2) bond formation, and a C–O coupling at the alkynyl position of the ynamides. This reaction proceeds under mild conditions and accepts a wide range of substrates. A number of tetrasubstituted amide enol 2-iodobenzoates bearing different functional groups were obtained in good to excellent yields. DFT calculations explain the observed regioselectivity. The synthetic potential of the reaction was further demonstrated by a number of selected follow-up transformations.

Topics & Concepts

ChemistryHypervalent moleculeStereoselectivityRegioselectivityEnolReagentCatalysisCombinatorial chemistryAmideAtom economyStereochemistryMedicinal chemistryOrganic chemistryCatalytic Alkyne ReactionsOxidative Organic Chemistry ReactionsCatalytic C–H Functionalization Methods
Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents | Litcius