First, attention was focused on the P(V) reagent itself, due to the high price and limited availability of Pentafluorothiophenol ($3,000/kg, Figure ). Fortunately, 4-bromothiophenol ($300/kg) was identified as a suitable alternative that is much easier to source on large scale and that ultimately reduced the cost of the leaving group by ten-fold. More importantly the P(V) reagent derived from this leaving group (Ψ Br ), was found to be competent in the preparation of nucleoside monomers (Figure .), while maintaining the same predictable and reproducible stereochemical outcome as the previously published PSI reagents (see SI for x-ray crystal structure of Ψ Br ). A series of conditions were evaluated to understand the loading of (Ψ Br ) onto nucleosides to afford P(V) monomers (Figure ). For this study, Benzoyl protected deoxycytidine (Bz-dC) was used as the model substrate. As expected, it was found that DBU plays a crucial role and cannot be replaced by other common bases such as DIPEA, imidazole, or Et3N (Figure , Entries 4-7).