Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 30, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202203807
Keywords
Cross-Coupling; Flow Chemistry; Metalation; Ring Openings; Sodium
Categories
Funding
- DFG
- LMU
- Projekt DEAL
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This study reports a lateral sodiation reaction for alkyl(hetero)arenes using a hexane-soluble sodium compound generated on demand, in the presence of TMEDA. The reaction can be conducted under batch and continuous flow conditions. The resulting benzylic sodium species can react with various electrophiles. This method has great potential for synthetic applications.
We report a lateral sodiation of alkyl(hetero)arenes using on-demand generated hexane-soluble (2-ethylhexyl)sodium (1) in the presence of TMEDA. (2-Ethylhexyl)sodium (1) is prepared via a sodium packed-bed reactor and used for metalations at ambient temperature in batch as well as in continuous flow. The resulting benzylic sodium species are subsequently trapped with various electrophiles including carbonyl compounds, epoxides, oxetane, allyl/benzyl chlorides, alkyl halides and alkyl tosylates. Wurtz-type couplings with secondary alkyl halides and tosylates proceed under complete inversion of stereochemistry. Furthermore, the utility of this lateral sodiation is demonstrated in the synthesis of pharmaceutical relevant compounds. Thus, fingolimod is prepared from p-xylene applying the lateral sodiation twice. In addition, 7-fold isotopically labeled salmeterol-d(7) and fenpiprane as well as precursors to super linear alkylbenzene (SLAB) surfactants are prepared.
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