Rapid Synthesis of Nucleoside Diphosphates Accelerated by Water

Abstract

While phosphate coupling typically requires anhydrous conditions, we describe a water-triggered rapid synthetic strategy for phosphoanhydride bond formation. By employing chloro(phenyl)trifluoromethyliodane (PhICF3Cl), a reagent traditionally reserved for trifluoromethylation, we successfully generated highly reactive phosphate donors. Upon the addition of a trace amount of water, these intermediates undergo nearinstantaneous coupling to yield various dinucleoside diphosphates (DNDPs). This protocol bypasses the sluggish kinetics of traditional methods, offering rapid access to various dinucleoside diphosphates.