AbstractAs an important class of nucleoside triphosphate analogues, α‐P‐modified nucleoside triphosphates (NTPαXs) have long been recognized as versatile tools in molecular biology and medicinal chemistry. However, the available synthetic methods based on modified nucleoside monophosphate and cyclic PVPVPIII‐nucleoside intermediates are only low to moderate‐yielding. Inspired by recent progress on PV‐PIII coupling reactions, we attempted to access NTPαXs via the putative linear PVPVPIII‐nucleoside intermediates. The current research found that a specific type of nucleoside phosphoramidites, fluorenylmethyl (Fm) nucleosidyl‐phosphoromorpholidites, are highly reactive in coupling with nBu4NH3P2O7 even without acidic activators. In situ oxidation of linear PVPVPIII‐nucleosides with specific sulfurizing, boranylating, and selenylating reagents followed by deprotection of α‐P and nucleoside moieties afforded NTPαXs (X=S, Se, and BH3) in excellent isolated yields. By exploiting dicyanoimidazole (DCI)’s promoting effect on PV‐PIII coupling, the current linear PVPVPIII‐nucleoside‐based method was further developed into an efficient route to α‐P‐modified dinucleoside tetraphosphates.