Abstract
A new Lewis acid promoted domino isocyanide insertion/5-exo-dig cyclization of readily available Strecker 3-component adducts to 4-substituted 5-aminoimidazole derivatives is herein reported. Despite their potential as relevant heterocyclic scaffolds in medicinal chemistry programs, this class of compounds is still underrepresented, with current synthetic strategies poorly efficient in terms of timing and yields. To this end, we show how the exploitation of unconventional reactivities of isocyanides, promoted by ytterbium-triflate, could represent a key resource to enable a fast and easy access to such an unexplored area of the chemical space.
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Depending on the substitution pattern, some derivatives could be better stored for prolonged times at -20°C as hydrochloride salts. They indeed showed to be unstable after several weeks at both room temperature and -20°C.
Acknowledgements
Financial support from Università degli Studi di Napoli “Federico II” and Università del Piemonte Orientale, Novara, Italy is acknowledged. R. C. acknowledges MIUR-Ministero dell’Istruzione, dell’Università e della Ricerca (Italian Ministry of Education, University and Research), PON R&I 2014-2020-AIM (Attraction and International Mobility), project AIM1873131—Num. Attività 2—Linea 2.1.
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Supplementary file1 (DOCX 13649 kb) Experimental synthetic procedures and copies of 1H- and 13C-NMR spectra for all the compounds reported in Supporting Information (PDF).
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Cannalire, R., Russo, C., Luciano, P. et al. Domino synthesis of 5-aminoimidazoles from Strecker multicomponent adducts via ytterbium-promoted isocyanide insertion/5-exo-dig cyclization. Mol Divers 27, 511–515 (2023). https://doi.org/10.1007/s11030-022-10418-4
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DOI: https://doi.org/10.1007/s11030-022-10418-4