53. A Catalyst-Free Flow Amination of Functional Organolithium Reagents
Heejin Kim, Yuya Yonekura, and Jun-ichi Yoshida, Angewandte Chemie International Edition, (2018) DOI: 10.1002/anie.201713031
We report an electrophilic amination of functional organolithium intermediates with well-designed aminating reagents under mild conditions using flow microreactors. The aminating reagents were explored and optimized to achieve an efficient C–N bond formation without using any catalyst. The electrophilic amination reactions of functionalized aryllithiums were successfully conducted under mild conditions within 1 min using flow microreactors. The aminating reagent was also prepared by the flow method. Based on stopped-flow NMR analysis, the reaction time for the preparation of the aminating reagent was quickly optimized without any necessity of work-up. Integrated one-flow synthesis consisting of generation of an aryllithium, the preparation of an aminating reagent, and their reaction was successfully achieved to give desired amine product within 5 min of total reaction time.