Phosphorochloridites phosphorochloridate

A synthetic approach to /3-sultams containing a direct bond between a tri- or tetracoordinated phosphorus atom and the nitrogen atom of the 1,2-thiazetidine 1,1-dioxide ring has been realized by direct phosphitylation or phosphorylation at nitrogen. Unfortunately, attempts to synthesize N-phosphorylated /3-sultams by reaction with diethyl phosphorochloridate and diethyl phosphorobromidate, generated in situ from diethyl phosphate and carbon tetrachloride or carbon tetrabromide, failed. However, when the /3-sultam is treated with freshly distilled diethyl phosphorochloridite or tetramethylphosphorodiamidous chloride in the presence of triethylamine, the expected AHliethy I phosphite and iV-phosphorodiamidous /3-sultams 150 are obtained (Equation 10). /3-Sultams unsubstituted... 

Esters of pyrophosphorous add can be prepared by using sodium dialkyl phosphite and a dialkyl phosphorochloridite (5.321). If a phosphorochloridate ester is used, an ester of hypophosphoric acid is obtained (5.322). 

An alternative synthesis of pyrophosphite esters is by condensation of alkyl phosphorochloridites using water and triethylamine (5.323), while another way of making hypophosphoric esters is by condensation of alkyl phosphorochloridates with sodium (5.324). 

Without additional reagents Cyclic phosphorochloridates from cyclic phosphorochloridites... 

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. 

---