Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

Org Lett. 2016 Apr 1;18(7):1694-7. doi: 10.1021/acs.orglett.6b00635. Epub 2016 Mar 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't