Trimethylsilyl Trifluoromethanesulfonate-promoted Reductive 2′-O-arylmethylation of Ribonucleoside Derivatives

Abstract

Arylmethyl groups such as benzyl, p-methoxybenzyl, and 1-pyrenylmethyl groups were introduced to the 2′-O-position of nucleosides by reductive etherification. Combining corresponding aromatic aldehydes with 2′-O-trimethylsilylnucleoside derivatives in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) resulted in moderate to good yields of the 2′-O-arylmethyluridine derivatives, whereas the corresponding cytidine and adenosine derivatives were obtained in low yields. The reaction of ribonucleosides with aliphatic aldehydes did not proceed smoothly. Anomerization of the uridine derivatives by TMSOTf was observed in CH₂Cl₂, toluene, and CH₃CN, but was completely suppressed when the reactions were conducted in 1,4-dioxane.

Keywords:

• 2′-O-modified ribonucleoside
• reductive etherification
• arylmethylation

Acknowledgments

The authors thank Professor Kazuhiko Saigo (Kochi University of Technology) for helpful suggestions. This work was financially supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Japan.