A Rapid, High-Yield Method for 5′-Hydroxyl Protection in Very Reactive and Amino Group Modified Nucleosides Using Dimethoxytrityl Tetrafluoroborate

The conventional method for 4,4′-dimethoxytrityl (DMT) etherification of the 5′-hydroxyl termini in deoxynucleosides that are either highly reactive or those bearing modifications at the exocyclic amino group can be quite problematic, and in several cases the yields are at best mediocre. Herein, we report a rapid, convenient and general procedure for the facile 5′-hydroxyl protection of these nucleosides in exceptionally high yields using DMT+BF4 −. This reagent is particularly useful for the preparation of 5′-O-DMT ethers of nucleosides that are either synthetically valuable or for those that undergo degradation under standard conditions.