Abstract
The formation of arene C–N bonds directly from C–H bonds is of great importance and there has been rapid recent development 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 obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the arene ortho position. 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 noncovalent interactions to control positional selectivity in radical reactions.
Highlights
The formation of arene C−N bonds directly from C−H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactive N-centered radicals
Aromatic amines are ubiquitous in pharmaceuticals, agrochemicals, and natural products
From Ritter and co-workers17 and Leonori and coworkers,15b have shown that careful tailoring of the structure of the aminium radical can result in high levels of para-selectivity (Figure 1b)
Summary
AYields and ratios were determined by 1H NMR with internal standard. Yield in parentheses is isolated. bNo iron catalyst. We questioned whether an N-methylated aminating agent may enable transfer of NHMe, allowing access to selectively monoalkylated ophenylenediamines.15c Pleasingly, use of 3d in place of 2d gave the aminomethylated product with an ortho:para selectivity of 17:1 and in good isolated yield (entry 16). The scope of NHMe transfer was evaluated and we were pleased to see high levels of ortho selectivity for a range of different aniline substrates (Scheme 1). Anilines bearing alkyl groups in the 2-position were well tolerated (4b, 4c), giving the aminated products with excellent ortho selectivity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
