Phosphorochloridite method synthesi

Lee, K., and Wiemer, D.E, Reaction of diethyl phosphorochloridite with enolates. A general method for synthesis of P-keto phosphonates and a-phosphono esters through C-P bond formation, J. Org. Chem., 56, 5556, 1991. 

Nucleoside Triphosphates and Their Analogues. - A review has been given of the most useful methods for the synthesis of nucleoside triphosphates. 5 -Triphosphates of 8-(alkylthio)adenosines have been prepared as inhibitors of nucleoside triphosphate diphosphohydrolase, and the triphosphates 202 and that derived from 2,2 -anhydrouridine have been made as agonists for P2X2-purinoceptors, but they showed lesser potencies than the parent nucleosides. Derivatives of ATP, UTP and CTP have been prepared in which methyl ketone groups are attached via spacers to the base units, in order to permit interaction with fluorescent probes after enzymic incorporation into oligonucleotides. The triphosphate was assembed by Eckstein s procedure, in which a 2, 3 -0-iso-propylidene nucleoside is treated sequentially with salicyl phosphorochloridite, pyrophosphate and an oxidant. ... 

Notice that the actual phosphodiester bond formation did not involve the reaction of a phosphorochloridate with the 5 -hydroxyl of the nucleoside. This approach has been seldom used for diester synthesis as these reactions tend to be sluggish and can be complicated by comparison with other methods. More favorable is the reaction of a nucleoside phosphorochloridite with a second molecule of nucleoside, as shall be discussed shortly. Alternatively, phosphodiester formation may be accomplished via in situ activation of a nucleotide with a condensing agent. Some of these reagents are described below. 

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