Scheme 1. Synthesis of bis-SATE protected phosphates. (A) The common approach for bis-SATE phosphotriester synthesis involves reaction of a substrate (R–OH) with phosphoramidite 1, followed by oxidation. Alternatively, after introduction of a monophosphate onto a substrate, a bis-bromoalkyl phospotriester intermediate 2 can be formed through esterification and the bromides subsequently substituted for thioacyl groups.20 (B) In this work, we describe a two-step approach involving triflic anhydride/pyridine-mediated selective monosubstitution of tri(2-bromoethyl)phosphate precursor 3 by a substrate, followed by substitution of the bromides for thioacetates.
