Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation

Arene
amination is achieved by site-selective C–H zincation
followed by copper-catalyzed coupling with O-benzoylhydroxylamines
under mild conditions. Key to this success is ortho-zincation mediated by lithium amidodiethylzincate base that is effective
for a wide range of arenes, including nonactivated arenes bearing
simple functionalities such as fluoride, chloride, ester, amide, ether,
nitrile, and trifluoromethyl groups as well as heteroarenes including
indole, thiophene, pyridine, and isoquinoline. An analogous C–H
azidation is also accomplished using azidoiodinane for direct introduction
of a useful azide group onto a broad scope of arenes and heteroarenes.
These new transformations offer rapid access to valuable and diverse
chemical space of aminoarenes. Their broad applications in organic
synthesis and drug discovery are demonstrated in the synthesis of
novel analogues of natural product (−)-nicotine and antidepressant
sertraline by late-stage amination and azidation reactions.