N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation

Masato Saito, Yu Kawamata, Michael Meanwell, Rafael Navratil, Debora Chiodi, Ethan Carlson, Pengfei Hu, Longrui Chen, Sagar Udyavara, Cian Kingston, Mayank Tanwar, Sameer Tyagi, Bruce P. McKillican, Moses G. Gichinga, Michael A. Schmidt, Martin D. Eastgate, Massimiliano Lamberto, Chi He, Tianhua Tang, Christian A. MalapitMatthew S. Sigman, Shelley D. Minteer, Matthew Neurock, Phil S. Baran

Research output: Contribution to journalArticlepeer-review

Abstract

The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.

Original languageEnglish (US)
Pages (from-to)7859-7867
Number of pages9
JournalJournal of the American Chemical Society
Volume143
Issue number20
DOIs
StatePublished - May 26 2021

Bibliographical note

Funding Information:
Financial support for this work was provided by National Science Foundation Center for Synthetic Organic Electrochemistry (CHE-2002158) and the National Institutes of Health (grant number GM-118176). M.S. was supported by a Postdoctoral Fellowship for Research Abroad (JSPS), R.N. was supported by an Experientia Foundation Fellowship, M.M. was supported by a Banting Postdoctoral Fellowship (NSERC), P.H. was supported by a George E. Hewitt Foundation Fellowship for Medical Research, and C.A.M was supported by the National Institute of General Medical Sciences of the National Institutes of Health (K99GM140249)

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