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 6 I - O -yl radical, which abstracts regioselectively the hydrogen at C5 II of the contiguous pyranose. The C5 II -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 1 C 4 conformation. The 6 I,IV - and 6 I,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 6 I,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.