Radical-mediated C–H functionalization : a strategy for access to modified cyclodextrins

Alvarez-Dorta, Dimitri and León, Elisa I. and Kennedy, Alan R. and Martin, Angeles and Pérez-Martín, Inés and Suárez, Ernesto (2016) Radical-mediated C–H functionalization : a strategy for access to modified cyclodextrins. Journal of Organic Chemistry, 81 (23). pp. 11766-11787. ISSN 0022-3263 (https://doi.org/10.1021/acs.joc.6b02241)

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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.