Chemoselective sequential click ligations directed by enhanced reactivity of an aromatic ynamine

Hatit, Marine Z. C. and Sadler, Joanna C. and McLean, Liam A. and Whitehurst, Benjamin C. and Seath, Ciaran P. and Humphreys, Luke D. and Young, Robert J. and Watson, Allan J. B. and Burley, Glenn A. (2016) Chemoselective sequential click ligations directed by enhanced reactivity of an aromatic ynamine. Organic Letters, 18 (7). pp. 1694-1697. ISSN 1523-7060 (https://doi.org/10.1021/acs.orglett.6b00635)

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Abstract

Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 +2] cycloaddition (“click”) reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups.

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