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 Rominger; Petra Krämer; A Stephen K Hashmi

doi:10.1021/acs.orglett.2c02161

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

Org Lett. 2022 Oct 7;24(39):7101-7106. doi: 10.1021/acs.orglett.2c02161. Epub 2022 Sep 22.

Authors

Yaowen Liu¹, Martin C Dietl¹, Chunyu Han¹, Matthias Rudolph¹, Frank Rominger¹, Petra Krämer¹, A Stephen K Hashmi^{1

2}

Affiliations

¹ Organisch Chemisches Institut, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
² Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

PMID: 36137218
DOI: 10.1021/acs.orglett.2c02161

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.