Synthesis and chemoselective ligations of MIDA acylboronates with O-Me hydroxylamines

Abstract

N-Methyliminodiacetyl (MIDA) acylboronates undergo chemoselective amide-bond forming ligations in water with O-Me hydroxylamines, including unprotected peptide substrates. These bench-stable boronates were easily prepared from potassium acyltrifluoroborates (KATs) in one step. The reactivity of MIDA acylboronates with O-alkylhydroxylamines – which are unreactive with KATs – was attributed to the nature of the neutral MIDA boronates versus the ionic KATs, leading to differences in the stability of likely intermediates and propensity for elimination.