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Synthesis 2023; 55(14): 2128-2133
DOI: 10.1055/a-2034-9427
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Synthesis of a Water-Soluble Tridentate (Dimethylamino)ethyl Cu(I)/Cu(II)-Ligand

T. Moritz Weber 
a   Institute of Bioorganic Chemistry, Heinrich Heine University at Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Stetternicher Forst, 52426 Jülich, Germany
,
Jörg Pietruszka  ∗
a   Institute of Bioorganic Chemistry, Heinrich Heine University at Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Stetternicher Forst, 52426 Jülich, Germany
b   Institute of Bio- and Geosciences (IBG-1: Biotechnology), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428 Jülich, Germany
› Author AffiliationsThis work was supported by the Deutsche Forschungsgemeinschaft (GRK 2158) and the Jürgen Manchot Foundation, Düsseldorf (scholarship to T.M.W.). We also thank Heinrich Heine University Düsseldorf and the Forschungszentrum Jülich GmbH for their ongoing support.
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Dedicated to A. Stephen K. Hashmi on the occasion of his 60th birthday

Abstract

Copper-catalyzed alkyne azide click chemistry (CuAAC) plays an important role in drug development and labeling of biological materials. Stabilizing ligands prevent Cu(I)-species from oxidation, increases the solubility of copper, and increases the acceleration of the catalyzed process. In this context, we report on the synthesis of a tris-amine tridentate Cu-ligand (TDETA), with terminal (dimethylamino)ethyl-substitution, which can be legally synthesized as a replacement of toxic nitrogen mustard HN3 as an intermediate and is a scalable alternative to the previously found amine ligand DTEA. The class II ligand TDETA exhibits excellent solubility properties in organic solvents and aqueous solutions, outcompetes the commercial class I ligands THPTA and TBTA for a broad range of azide and alkyne combinations using Cu(I)- and Cu(II)-species, and was shown to be recoverable in a yield of 80%.

Key words

click chemistry - ligand - azide - alkyne - cycloaddition - copper

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2034-9427.
  • Supporting Information


Publication History

Received: 22 November 2022

Accepted after revision: 14 February 2023

Accepted Manuscript online:
14 February 2023

Article published online:
22 March 2023

© 2023. Thieme. All rights reserved

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