Protecting Group-Free Remote Desaturation via O-Benzoyl Hydroxylamines
Loading...
Date
2023-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
Despite its immense synthetic potential, the functionalization of unactivated C-H bonds remains a challenging topic in modern organic chemistry. Due to the prevalence of these bonds, any potential C-H functionalization reaction must be selective enough to prevent the formation of an undesirable mixture of products. One of the earliest attempts at addressing the selectivity challenge would be the Hofmann–Löffler–Freytag (HLF) reaction, which proceeds through an entropically and enthalpically favored 1,5-Hydrogen Atom Transfer (HAT) pathway to generate a carbon-centered radical δ to an amine. However, despite its inherent regioselectivity, the traditional HLF reaction possesses several drawbacks, such as requiring elevated temperatures and solvent quantities of sulfuric acid, which significantly limits its applicability. Recently, our group has developed a milder, protecting group-free alternative to the traditional HLF reaction that can achieve remote desaturation of a broad library of o-benzoyl hydroxylamines. The method is tolerant of a variety of functional groups commonly encountered in organic synthesis and drug discovery, making it a powerful tool for the late-stage diversification and post-functionalization of potential drug candidates.
Description
Keywords
Protecting Group-Free, C-H Functionalization, Robustness Screen, HLF Reaction