Hikotada. Tsuboi

A convenient synthesis of 6-, 7-, and 8-membered cyclic phosphodiesters

1,3-, 1,4-, and 1,5-Alkanediols are converted into the corresponding 6-, 7-, and 8- membered cyclic phosphodiesters in a two-step procedure utilizing N-(1,2-dimethylethylene-dioxyphosphoryl)imidazole (2 as the sole phosphorylating reagent.

PHOSPHORYLATION OF ALCOHOLS BY CYCLIC PHOSPHODIESTERS IN APROTIC SOLVENTS

Abstract The reactions of alcohols with 4,5-dimethyl-2-hydroxy-2-oxo-2H-1,3,2-dioxaphosphole and 4,5-dimethyl-2-alkoxy-2-oxo-2H-1,3,2-dioxaphosphole have been studied in 0.2 M CD2Cl2 solutions at 25°. The data show that, the phosphorylation of alcohols in aprotic solvents of relatively low polarity are faster with a cyclic enediol phosphodiester than with the corresponding phosphotriester. The alcohol-phosphotriester reactions are catalyzed by trifluoroacetic and acetic acids, and the acid-catalyzed rates are still somewhat slower than the acid-autocatalyzed rates of the alcohol-phosphodiester reactions. It is suggested that both types of phosphorylation involve protonation of the phosphoryl-oxygen and formation of an intermediate with pentacoordinate phosphorus (‘oxyphosphorane’ or ‘addition-elimination’ mechanism). Steric effects in the alcohol and in the phosphorylating reagents play an important role in this mechanism. The conjugate base of the cyclic enediol phosphodiester fails to react with alcohol...