A very mild and efficient procedure has been developed for the preparation of -methylated uridine, pseudouridine, guanosine and inosine derivatives. This process was compatible with free hydroxyls within the ribose and did not require precautions on the protection or deprotection of other functionalities. The key to this extremely mild methylation without protection relied on the generated methyl oxonium from the Wittig reagent and methanol. A putative mechanism for the selective methylation was also proposed.
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