DOI: 10.1021/acs.orglett.6c04072 ISSN: 1523-7060
Bromine-Enabled Halogen-Bond-Promoted Electrochemical 16O/18O-Incorporation for Skeletal Editing of N -Heterocycles
Yi-Min Jiang, Hong Xu, Cheng-Lin Ding, Qilin Yang, Guizhen Zhang, Shuangqiang Tang, Junsheng Pu, Tianruo Shen, Yu Zheng, Hongbao Sun, Jie LiuAbstract
Incorporating oxygen into N-heterocycles with simultaneous isotopic labeling remains challenging. Here, we report a metal-, oxidant-, and base-free electrochemical platform using water as the oxygen source for 16O/18O incorporation. Bromide acts as both a redox mediator and halogen-bond activator, with generated Br2 enhancing substrate electrophilicity and promoting hydroxide attack. The method enables skeletal editing of tetrazines and pyrazines and peripheral editing of tetrazoles and triazines, affording 18O-labeled products with up to 99% enrichment and broad functional-group tolerance.