(2‐Ethylhexyl)sodium: A Hexane‐Soluble Reagent for Br/Na‐Exchanges and Directed Metalations in Continuous Flow. Issue 26 (3rd May 2021)

• Record Type: Journal Article
• Authors: Harenberg, Johannes H.; Weidmann, Niels; Wiegand, Alexander J.; Hoefer, Carla A.; Annapureddy, Rajasekar Reddy; Knochel, Paul
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 26(2021)
• Page Start: 14296
• Page End: 14301
• Publication Date: 2021-05-03
• Subjects: Br/Na-exchange -- directed sodiation -- flow chemistry -- packed-bed reactor -- sodium; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202103031
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: We report the on‐demand generation of hexane‐soluble (2‐ethylhexyl)sodium (1 ) from 3‐(chloromethyl)heptane (2 ) using a sodium‐packed‐bed reactor under continuous flow conditions. Thus, the resulting solution of 1 is free of elemental sodium and therefore suited for a range of synthetic applications. This new procedure avoids the storage of an alkylsodium and limits the handling of metallic sodium to a minimum. (2‐Ethylhexyl)sodium (1 ) proved to be a very useful reagent and undergoes in‐line Br/Na‐exchanges as well as directed sodiations. The resulting arylsodium intermediates are subsequently trapped in batch with various electrophiles such as ketones, aldehydes, Weinreb‐amides, imines, allyl bromides, disulfides and alkyl iodides. A reaction scale‐up of the Br/Na‐exchange using an in‐line electrophile quench was also reported. Abstract : A generation of sodium metal free, hexane‐soluble (2‐ethylhexyl)sodium using a sodium‐packed‐bed reactor in a continuous flow set‐up was reported. (2‐Ethylhexyl)sodium proved to be a very useful sodium organometallic reagent and was used for in‐line sodiations as well as Br/Na‐exchange reactions. The arylsodiums were trapped with various electrophiles. A reaction scale‐up of the Br/Na‐exchange using an in‐line electrophile quench was reported.