Phosphorochloridite method

The very high accuracy which may be obtained by the pulsed Fourier transform method has been demonstrated using o-phenylene phosphorochloridite.1... 

The mono- to tetraethylene glycol modified phosphites 14a-d have been synthesized according to the first-described method starting from commercially available (o-phenylene) phosphorochloridite 13 in > 90% yield (Scheme 2). 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

Reaction of an alcohol with the reagent o-phenylene phosphorochloridite followed by treatment of the alkyl o-phenylene phosphite so obtained with iodine in dichloromethane at room temperature results in a good yield of alkyl iodide. This method, exemplified by the preparation of 1-iodoheptane (Expt 5.60), is the preferred procedure when acid-sensitive functional groups are present. 

Diphenyl phosphorochloridite can be prepared from phenol and phosphorus (III) chloride, but a mixture of products is produced and the yield of the desired compound is low. Higher yields can be obtained from reaction of triphenyl phosphite with phosphorus(III) chloride, but this method is inconvenient because it involves a reaction which... 

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. 

Hydroxy-2,2-diphenylethyl phenyl sulfide allowed to react with methyllithium in tetrahydrofuran, then at 0 with o-phenylene phosphorochloridite, and the intermediate crude phosphorous ester refluxed 3 hrs. in dioxane 1,1-diphenyl-ethylene. Y 83%. F. e. s. I. Kuwajima, S. Sato, and Y. Kurata, Tetrah. Let. 1972, 737 f. method cf. R. M. Coates and R. L. Sowerby, Am. Soc. 94, 5386 (1972). 

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