Triaryl carbonium ion-pair-mediated cooperative aerobic dehydrogenation of N-heterocycles

• Main Authors: Zhang, Zhenguo, Gu, Jun, Ji, Liang, Liu, Xiaoxiao, Zhang, Ting, Lv, Yongheng, Liu, Fang, Jia, Zhenhua, Loh, Teck-Peng
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Chemistry; Metal Free; Ion Pair
• Online Access: https://hdl.handle.net/10356/171494
• Institution: Nanyang Technological University

The triphenylmethyl radical was discovered by Gomberg in 1900 and has been shown to be a persistent radical species. Surprisingly, this radical is rarely used in organic synthesis since its discovery over a century ago. Here, we report a metal-free aerobic dehydrogenation of N-heterocycles mediated by a triphenylmethyl radical generated from a triaryl carbonium ion pair as the precatalyst in the presence of TEMPO. This protocol exhibits a broad substrate scope and excellent functional group tolerance. The practicality has also been demonstrated with the gram-scale preparation of key intermediates of small-molecule drugs and late-stage functionalization of various dipine drugs. Mechanistic studies and DFT calculations revealed that the triphenylmethyl radical was involved in the catalytic cycle and was essential for the aerobic dehydrogenation process.