Rapid synthesis of nucleoside diphosphates accelerated by water

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 near-instantaneous coupling to yield various dinucleoside diphosphates (DNDPs). This protocol bypasses the sluggish kinetics of traditional methods, offering rapid access to various dinucleoside diphosphates.