Palladium(0)-Catalyzed Arylation of Resin-Bound Imidazol-2-ylzinc Chlorides

Abstract

1-Hydroxyimidazole loaded on Wang resin under Mitsunobu conditions was selectively deprotonated at C-2 by BuLi. The anion formed was then reacted with electrophiles or transmetallated with zinc chloride to give resin-bound imidazolylzinc chloride which was cross-coupled with aryl and heteroaryl iodides under palladium(0) catalysis. Cleavage using TFA-CH₂Cl₂ (1:1) at room temperature afforded 2-aryl/heteroaryl substituted 1-hydroxyimidazoles.

Keywords

solid-phase synthesis - cross-coupling - palladium - zinc compounds - 1-hydroxyimidazole

References

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29

Initially Wang bound 1-hydroxyimidazole was obtained as described previously [27] by reaction of the sodium salt of 1 with the chloromethyl Wang resin prepared from commercially available Wang resin (100-200 Mesh, Novabiochem, loading 0.83 mmol/g). [34] Upon lithiation followed by reaction with an electrophile this resin gave lower conversion (ca. 75%) than the resin loaded using modified Mitsunobu conditions although the MAS-NMR spectra of the two loaded resins were identical.