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β C-H di-halogenation via iterative hydrogen atom transfer
Ethan A Wappes1, Avassaya Vanitcha1, David A Nagib1
1The Ohio State University , Department of Chemistry and Biochemistry , Columbus , OH 43210 , USA .
Chemical Science
|June 14, 2018
Summary
A new radical relay strategy enables selective mono- and di-halogenation of sp3 C-H bonds. This method achieves the first example of beta C-H di-halogenation using iterative hydrogen atom transfer (HAT).
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Radical Chemistry
Background:
- C-H bond functionalization is crucial for organic synthesis.
- Developing selective methods for di-halogenation of sp3 C-H bonds remains challenging.
- Radical relay strategies offer a promising avenue for complex molecule synthesis.
Purpose of the Study:
- To develop a novel radical relay strategy for mono- and di-halogenation of sp3 C-H bonds.
- To achieve the first example of beta C-H di-halogenation.
- To explore the utility of imidate radicals in sequential C-H functionalization.
Main Methods:
- Development of a radical relay strategy involving iterative hydrogen atom transfer (HAT).
- Utilisation of in situ generated imidate radicals for radical translocation.
- Tunable C-X termination for selective halogenation (iodination, bromination, chlorination).
Main Results:
- Successful mono- and di-halogenation of sp3 C-H bonds.
- Demonstration of the first beta C-H di-halogenation via sequential HAT.
- Versatile geminal di-iodide products were synthesized and further elaborated.
- Mechanistic studies revealed the second C-H iodination is twice as fast as the first.
Conclusions:
- The developed radical relay strategy provides a powerful new tool for C-H functionalization.
- The iterative HAT pathway enables selective and efficient di-halogenation.
- The methodology opens new routes for synthesizing complex organic molecules and intermediates.
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