Chemoselective Amide-Forming Ligation Between Acylsilanes and Hydroxylamines Under Aqueous Conditions

Abstract

We report the facile amide-forming ligation of acylsilanes with hydroxylamines (ASHA ligation) under aqueous conditions. The ligation is fast, chemoselective, mild, high-yielding and displays excellent functional-group tolerance. Late-stage modifications of an array of marketed drugs, peptides, natural products, and biologically active compounds showcase the robustness and functional-group tolerance of the reaction. The key to the success of the reaction could be the possible formation of the strong Si-O bond via a Brook-type rearrangement. Given its simplicity and efficiency, this ligation has the potential to unfold new applications in the areas of medicinal chemistry and chemical biology.

Keywords: acylsilanes; amide bond; aqueous reactions; chemoselectivity; ligation reactions.