Uncovering the Untapped Potential of the Use of Sodium Amides for Regioselective Arene Functionalisation

Authors

  • Andreu Tortajada Departement für Chemie, Biochemie und Pharmazie, Universität Bern, CH-3012 Bern
  • Eva Hevia Departement für Chemie, Biochemie und Pharmazie, Universität Bern, CH-3012 Bern https://orcid.org/0000-0002-3998-7506

DOI:

https://doi.org/10.2533/chimia.2023.225

PMID:

38047801

Keywords:

Alkali metal, Amide, Borylation, Deuteration, Sodium

Abstract

Alkali-metal amides have become key reagents in synthetic chemistry, with special focus in deprotonation reactions. Despite the higher reactivity found in the heavier sodium and potassium amides, their insolubility and low stability has favoured the use of the more soluble  lithium analogues, converting them into the most used non-nucleophilic bases. Studying the coordination effects of Lewis donor molecules such as tridentate amine PMDETA (N,N,N’,N’’,N’’-pentamethyldiethylenetriamine) in combination with the sodium amide NaTMP (TMP = 2,2’,6,6’-tetramethylpiperidide), we have been able to unlock the use of these reagents for the functionalisation of arenes, i.e. the deuterium incorporation by hydrogen isotope exchange and the deprotonative borylation of unactivated arenes. These findings show how sodium amides are not just a simple more sustainable replacement of their lithium counterparts, but also that they can display significantly enhanced reactivities allowing for the development of new transformations.

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Published

2023-04-26