Abstract
The TEMPO oxoammonium cation has been proven to be both an efficient oxidizing reagent and an electrophilic substrate frequently found in organic reactions. Here, we report that this versatile chemical reagent can also be used as an efficient promoter for C- and N-glycosylation reactions through a Ferrier rearrangement with moderate to high yields. This unprecedented reactivity is explained in terms of a Lewis acid activation of glycal by TEMPO(+) forming a type of glycal-TEMPO(+) mesomeric structure, which occurs through an extended vinylogous hyperconjugation toward the π*((O═N(+))()) orbital [LP((O1)) → π*((C1═C2)), π*((C1═C2)) → σ*((C3-O3)), and LP((O6)) → π*((O═N)(+)())]. This enables the formation of the respective Ferrier glycosyl cation, which is trapped by various nucleophiles. The extended hyperconjugation (or double hyperconjugation) toward the π*((O═N(+))()) orbital, which confers the Lewis acid character of the TEMPO cation, was supported by natural bond orbital analysis at the M06-2X/6-311+G** level of theory.