Regioselective Radical Arene Amination for the Concise Synthesis of ortho-Phenylenediamines
Published version
Peer-reviewed
Repository URI
Repository DOI
Type
Change log
Authors
Abstract
The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent de-velopment of methods for achieving this through radical mechanisms, often involving reactive N-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products ob-tained in most protocols, limiting broader utility. We have designed a system that utilizes attractive non-covalent interactions between an anionic substrate and an incoming radical cation in order to guide it to the arene ortho posi-tion. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly to ortho-phenylenediamines, key building blocks for a range of medicinally-relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuable ortho-phenylenediamines, this work demonstrates the potential for utilizing non-covalent interactions to control positional selectivity in radical reactions.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
1520-5126
Volume Title
Publisher
Publisher DOI
Sponsorship
European Research Council (757381)
Engineering and Physical Sciences Research Council (EP/S03269X/1)
Royal Society (URF\R\191003)