A Radical-Initiated Fragmentary Rearrangement Cascade of Ene-Ynamides to [1,2]-Annulated Indoles via Site-Selective Cyclization

Sifan Li; Yu Wang; Zibo Wu; Weiliang Shi; Yibo Lei; Paul W Davies; Wei Shu

doi:10.1021/acs.orglett.1c02519

A Radical-Initiated Fragmentary Rearrangement Cascade of Ene-Ynamides to [1,2]-Annulated Indoles via Site-Selective Cyclization

Org Lett. 2021 Sep 17;23(18):7209-7214. doi: 10.1021/acs.orglett.1c02519. Epub 2021 Aug 28.

Authors

Sifan Li^{1

2}, Yu Wang¹, Zibo Wu³, Weiliang Shi³, Yibo Lei³, Paul W Davies², Wei Shu¹

Affiliations

¹ Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, P.R. China.
² School of Chemistry, University of Birmingham, Edgbaston, BirminghamB15 2TT, U.K.
³ Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, P.R. China.

PMID: 34459193
DOI: 10.1021/acs.orglett.1c02519

Abstract

Straightforward access to [1,2]-annulated indoles, key substructures in natural products, is highly desirable yet challenging. Herein, a radical triggered fragmentary cyclization cascade reaction of ene-ynamides is presented, providing a rapid access into [1,2]-annulated indoles by an intermolecular radical addition, intramolecular cyclization, desulfonylative aryl migration, and site-selective C(sp²)-N cyclization sequence. DFT calculations support oxidation of N-centered radical species to cations prior to the C-N bond formation, followed by an unusual aza-Nazarov cyclization.