C-H Amination of Arenes and Heteroarenes through a Dearomative (3 + 2) Cycloaddition

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Direct C-H amination of arenes avoids substrate pre-functionalization, unlike traditional halogenation or metalation methods.
• Existing C-H amination often relies on transition metal or photoredox catalysis via electrophilic substitution, radical addition, or nitrene insertion mechanisms.

Purpose of the Study:

• To develop a novel, efficient, and versatile method for the direct C-H amination of unactivated arenes and heteroarenes.
• To explore the mechanism involving azidium ions, cycloaddition, and subsequent bond cleavage for arylamine synthesis.

Main Methods:

• Telescoped C-H amination using azidium ions.
• Dearomative (3 + 2) cycloaddition to form triazolinium adducts.
• Base treatment followed by thermolysis to yield arylamines.

Main Results:

• Successfully synthesized a diverse range of arylamines from unactivated arenes and heteroarenes.
• Demonstrated broad substrate scope, including late-stage amination of natural products, pharmaceuticals, agrochemicals, and functional materials.
• Achieved unique regioselective postsynthetic double C-H aminations of coronene and [9]cycloparaphenylene.

Conclusions:

• Azidium ion-mediated C-H amination provides a complementary approach to existing methods, offering distinct regio- and site-selectivity.
• The developed protocol is versatile and efficient for synthesizing valuable arylamine compounds.
• This method opens new avenues for C-H functionalization in complex molecule synthesis.