Radical-Mediated C–H Functionalization: A Strategy for Access to Modified Cyclodextrins

A simple
and efficient radical C–H functionalization to access modified
cyclodextrins (CDs) has been developed. The well-defined conformation
of glycosidic and aglyconic bonds in α-, β-, and γ-CDs
favors the intramolecular 1,8-hydrogen atom transfer (HAT) promoted
by the 6I-O-yl radical, which abstracts
regioselectively the hydrogen at C5II of the contiguous
pyranose. The C5II-radical evolves by a polar crossover
mechanism to a stable 1,3,5-trioxocane ring between two adjacent glucoses
or alternatively triggers the inversion of one α-d-glucose
into a 5-C-acetoxy-β-l-idose unit
possessing a 1C4 conformation.
The 6I,IV- and 6I,III-diols of α- and
β-CDs behave similarly to the monoalcohols, forming mostly compounds
originating from two 1,8-HAT consecutive processes. In the case of
6I,II-diols the proximity of the two 6-O-yl radicals in adjacent sugar units allows the formation of unique
lactone rings within the CD framework via a 1,8-HAT−β-scission
tandem mechanism. X-ray diffraction carried out on the crystalline
1,4-bis­(trioxocane)-α-CD derivative shows a severe distortion
toward a narrower elliptical shape for the primary face.