Radical-Mediated C-H Functionalization: A Strategy for Access to Modified Cyclodextrins.
Dimitri Alvarez-Dorta1, Elisa I León1, Alan R Kennedy2
1Síntesis de Productos Naturales, Instituto de Productos Naturales y Agrobiología del CSIC , Carretera de La Esperanza 3, 38206, La Laguna, Tenerife, Spain.
The Journal of Organic Chemistry
|November 3, 2016
Summary
A new radical C-H functionalization method modifies cyclodextrins (CDs) by forming unique trioxocane and lactone rings. This efficient process alters CD structure and conformation, offering novel derivatives for various applications.
Area of Science:
- Carbohydrate Chemistry
- Organic Synthesis
- Supramolecular Chemistry
Background:
- Cyclodextrins (CDs) are cyclic oligosaccharides with a well-defined toroidal structure.
- Modifying CDs is crucial for tailoring their properties for specific applications.
- Existing methods for CD modification can be complex and lack regioselectivity.
Purpose of the Study:
- To develop a simple and efficient radical C-H functionalization method for cyclodextrins.
- To explore the regioselective modification of α-, β-, and γ-cyclodextrins.
- To synthesize novel cyclodextrin derivatives with unique structural features.
Main Methods:
- Intramolecular 1,8-hydrogen atom transfer (HAT) promoted by 6I-O-yl radicals.
- Regioselective hydrogen abstraction at the C5II position of contiguous pyranose units.
- Polar crossover mechanism and tandem reaction pathways (HAT-β-scission).
- X-ray diffraction analysis of modified cyclodextrin derivatives.
Main Results:
- Successful regioselective functionalization of α-, β-, and γ-cyclodextrins.
- Formation of stable 1,3,5-trioxocane rings between adjacent glucose units.
- Inversion of α-d-glucose to 5-C-acetoxy-β-l-idose units.
- Generation of unique lactone rings within the cyclodextrin framework from 6I,II-diols.
- X-ray analysis revealed significant structural distortion in a bis(trioxocane)-α-CD derivative.
Conclusions:
- A novel and efficient radical C-H functionalization strategy for cyclodextrins has been established.
- The method allows for the regioselective synthesis of diverse cyclodextrin derivatives.
- The generated modifications, such as trioxocane and lactone rings, significantly alter cyclodextrin structure and conformation.
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