A Mild Preparation of Protected Phosphate Esters from Alcohols

摘要

Treatment of a wide variety of alcohols with trimethyl phosphite and carbon tetrabromide in pyridine leads to the formation of the corresponding dimethyl phosphate esters in high yields. The reaction is presumed to proceed by formation of an intermediate alkoxy trimethoxyphosphonium salt which undergoes selective demethylation by bromide. Poor yields are generally obtained if solvents other than pyridine are employed or if carbon tetrabromide is replaced by carbon tetrachloride. The mildness of the procedure is illustrated by the conversion of the highly acid sensitive 2-(4,4′-dimethoxytrityloxy)-1-phenylethanol to its dimethyl phosphate ester (74%) and the base sensitive N-CBZ-tyrosine p-nitrophenyl ester to the corresponding O-(dimethyl phosphate ester) (82%). The availability of methods for the demethylation of methyl phosphate esters makes this oxidative phosphorylation reaction a mild and inexpensive method for the synthesis of protected phosphate esters.