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Indole Rearrangemen Manuscript.pdf (3.07 MB)

Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides

preprint
submitted on 13.01.2021, 22:56 and posted on 18.01.2021, 06:15 by Vaishnavi Nair, Volga Kojasoy, Croix Laconsay, Dean Tantillo, Uttam Tambar
We have developed catalyst-controlled regiodivergent rearrangements of onium-ylides derived from indole substrates. Oxonium ylides formed in situ from substituted indoles selectively undergo [2,3]- and [1,2]-rearrangements in the presence of a rhodium and copper catalyst, respectively. The combined experimental and density functional theory (DFT) computational studies indicate divergent mechanistic pathways involving a metal-free ylide in the rhodium catalyzed reaction favoring [2,3]-rearrangement, and a metal-coordinated ion-pair in the copper catalyzed [1,2]-rearrangement that recombines in the solvent-cage. The application
of our methodology was demonstrated in the first total synthesis of the indole alkaloid (±)-sorazolon B, which enabled the stereochemical reassignment of the natural product. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also demonstrated.

Funding

W. W. Caruth, Jr. Endowed Scholarship

Welch Foundation (I-1748)

National Institutes of Health (R01GM102604)

American Chemical Society Petroleum Research Fund (59177-ND1)

Teva Pharmaceuticals Marc A. Goshko Memorial Grant (60011-TEV)

Sloan Research Fellowship

Sarah and Frank McKnight Fund Graduate Fellowship

National Science Foundation (CHE-1856416 and XSEDE via CHE-030089)

History

Email Address of Submitting Author

Uttam.Tambar@UTSouthwestern.edu

Institution

University of Texas Southwestern Medical Center

Country

United States

ORCID For Submitting Author

0000-0001-5659-5355

Declaration of Conflict of Interest

The authors declare no conflict of interest.