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DOI: 10.1055/s-0028-1083394
A New Solid-Phase Linker: Cu-Assisted Amide Bond Cleavage
Contributor(s):Yasuhiro Uozumi, Yoichi M. A. Yamada, Maki MinakawaAlbert-Ludwigs-Universität Freiburg, Germany
Forced Complexation of Nitrogen Leading to a Weakening of Amide Bonds: Application to a New Linker for Solid-Phase Chemistry
Eur. J. Org. Chem. 2008, 4412-4415
Publication History
Publication Date:
23 October 2008 (online)
Key words
amides - copper - cleavage - solid-phase synthesis
Significance
A chemically robust linker for solid-phase synthesis is reported, which is cleaved by Cu²+-assisted methanolysis. Thus, HypoGel-400-supported 2 underwent peptide synthesis (A), reduction amination (B), Suzuki-Miyaura coupling (C), and ring-closing metathesis (D) to give the corresponding amides 3A-D. Treatment of 3 with an equimolar amount of Cu(OTf)2 in methanol led to methanolysis of the amide bond, giving the corresponding methyl esters (5A-D) in 31-50% overall yield from 1.
Comment
The authors also show the recycling of used linker 4. Treatment with a methanolic solution of potassium cyanide was used for the regeneration of 2. The linker was stable under acidic (50% TFA in CH2Cl2) and basic (0.2 M LiOH in H2O) conditions as well as in the presence of fluoride ions (0.1 M Bu4NF in THF).