N-Ammonium Ylide Mediators for Selective Electrochemical C–H Oxidation

The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organicsynthesis. From simplifying access to metabolites and late-stage diversification of lead compoundsto truncating retrosynthetic plans, there is a growing need for new reagents and methods forachieving such a transformation in both academic and industrial circles. One main drawback ofcurrent chemical reagents is the lack of diversity with regards to structure and reactivity thatprevent a combinatorial approach for rapid screening to be employed. In that regard, directedevolution still holds the greatest promise for achieving complex C–H oxidations in a variety ofcomplex settings. Herein we present a rationally designed platform that provides a step towardsthis 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 buildingblocks and trivial synthesis techniques. The ylide-based approach to C–H oxidation exhibitstunable selectivity that is often exclusive to this class of oxidants and can be applied to real worldproblems in the agricultural and pharmaceutical sectors.