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(2‐Ethylhexyl)sodium: A Hexane‐Soluble Reagent for Br/Na‐Exchanges and Directed Metalations in Continuous Flow
Author(s) -
Harenberg Johannes H.,
Weidmann Niels,
Wiegand Alexander J.,
Hoefer Carla A.,
Annapureddy Rajasekar Reddy,
Knochel Paul
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103031
Subject(s) - chemistry , reagent , electrophile , hexane , sodium , alkyl , flow chemistry , heptane , organic chemistry , combinatorial chemistry , catalysis
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.