The tyrosine \%O\%\|phosphorylation \%via\% Atherton\|Todd reaction, which was a classical reaction for phosphorylation amines, was first studied in this paper. Reaction of Boc\|Tyr\|OCH\-3, which was selected as model substrate, with three dialkyl \%H\%\|phosphonate diester in the presence of CCl\-4 and triethylamine produced the corresponding tyrosine \%O\%\|phosphorylation products in a high yield(over 80%). The reaction was conducted in anhydrous THF solution and monitored by \{\}\+\{31\}P NMR and TLC. Then reaction of Boc\|Tyr\|OCH\-3 with a complicated H\|phosphonate diester, \%O\%\|3\|acetylthymidin\|5\|yl \%O\%\|isopropyl \%H\%\|phosphonate diester, also gave a good result and this would be an alternative approach for the synthesis of nucleotide \%O\%\|tyrosine (or tyrosine containing peptide) conjugate. Further, the successful \%O\%\|phosphoration of three tyrosine containing protected dipeptides, Boc\|Tyr\|Val\|OCH\-3, Boc\|Ala\|Tyr\|OCH\-3, Boc\|Tyr\|Tyr\|OCH\-3, with diisopropyl \%H\%\|phosphonate diester demonstrated the effectiveness of the method.
