A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare, yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than sixteen-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications. File list (2) download file view on ChemRxiv BMS Diastereoselective Synthesis Thiophosphoramidat... (396.86 KiB) download file view on ChemRxiv BMS Diastereoselective CDN Synthesis-Supporting Inform... (1.83 MiB)