A Catalyst‐Free Amination of Functional Organolithium Reagents by Flow Chemistry. Issue 15 (7th March 2018)

• Record Type: Journal Article
• Authors: Kim, Heejin; Yonekura, Yuya; Yoshida, Jun‐ichi
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 15(2018)
• Page Start: 4063
• Page End: 4066
• Publication Date: 2018-03-07
• Subjects: amination -- flow chemistry -- microreactors -- NMR spectroscopy -- organolithiums; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201713031
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Reported is the electrophilic amination of functional organolithium intermediates with well‐designed aminating reagents under mild reaction conditions using flow microreactors. The aminating reagents were optimized to achieve efficient C−N bond formation without using any catalyst. The electrophilic amination reactions of functionalized aryllithiums were successfully conducted under mild reaction conditions, within 1 minute, by 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 the necessity of work‐up. Integrated one‐flow synthesis consisting of the generation of an aryllithium, the preparation of an aminating reagent, and their combined reaction was successfully achieved to give the desired amine within 5 minutes of total reaction time. Abstract : Go with the flow : Reported is the electrophilic amination of organolithium intermediates using optimized amine reagents under mild reaction conditions within flow microreactors. Flow reactions are suitable for fast and mild amination using unstable organolithium compounds. Also notable is the fact that additional reagents and catalysts were not necessary. FG=functional group, R 1 and R 2 =alkyl groups.