Open AccessN-Ammonium Ylide Mediators for Electrochemical C–H Oxidation
Author(s) -
Masato Saito,
Yu Kawamata,
Michael Meanwell,
Rafael Navrátil,
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. Malapit,
Matthew S. Sigman,
Shelley D. Minteer,
Matthew Neurock,
Phil S. Baran
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c03780
Subject(s) - chemistry , reagent , combinatorial chemistry , ylide , organic synthesis , electrochemistry , ammonium , reactivity (psychology) , organic chemistry , catalysis , electrode , medicine , alternative medicine , pathology
The site-specific oxidation of strong C(sp 3 )-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(sp 3 )-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.