Phosphoramidite analogues of modified cyclotriphosphates provide a general and step-economical synthesis of nucleoside triphosphates and analogues on scale without the need for protecting groups. These reagents enable rapid access to pure nucleoside oligophosphates and a range of other analogues that were previously difficult to obtain (e.g., NH, CH2, CCl2, and CF2 replacements for O, phosphono- and phosphoimidazolides, -morpholidates, -azidates, and -fluoridates). DFT calculations demonstrate that the selectivity of the cyclotriphosphate opening reactions proceeds via an in-line substitution mechanism that displaces the least charged leaving group.