Clarifying the Unknown Mechanism of the Removal of the 4-Nitrobenzyloxymethyl Group via a Benzyl Radical Intermediate Induced by Tetra- n -butylammonium Fluoride

In synthesizing RNA, the 4-nitrobenzyloxymethyl (4-NBOM) group is a 2′-hydroxyl-protecting group removable via treatment with tetra-n-butylammonium fluoride, but its deprotection mechanism has remained unknown for decades. We determined that the deprotection of 4-NBOM-uridine afforded uridine and 4-nitrobenzoic acid. The results of extensive experiments suggested that deprotection occurs via single-electron transfer from the generated benzyl anion to O2, followed by rebinding between the resultant benzyl radical and O2•– species.