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

摘要

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 amido diethylzincate base that is effective for a wide range of arenes, including non-activated 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, diverse chemical space of aminoarenes. Their broad applications in organic synthesis and drug discovery are demonstrated in the synthesis of novel analogs of natural product (–)-nicotine and antidepressant sertraline by late-stage amination and azidation reactions.