(2-Ethylhexyl)sodium: A Hexane-Soluble Reagent for Br/Na-Exchanges and Directed Metalations in Continuous Flow

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.

Automated summary

The study demonstrates a novel method for the on-demand generation of (2-ethylhexyl)sodium from 3-(chloromethyl)heptane using a sodium-packed-bed reactor under continuous flow conditions, producing a solution free of elemental sodium suitable for various synthetic applications. The new procedure eliminates the need for storing alkylsodium and minimizes the handling of metallic sodium, enhancing safety in laboratory experiments. The (2-ethylhexyl)sodium reagent proves to be highly versatile, allowing for in-line Br/Na-exchanges and directed sodiations with subsequent trapping of arylsodium intermediates with various electrophiles in batch reactions.