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Aromatic C-H amination in hexafluoroisopropanol
Erica M D'Amato1, Jonas Börgel2, Tobias Ritter1,2
1Department of Chemistry and Chemical Biology , Harvard University , 12 Oxford Street , Cambridge , Massachusetts 02138 , USA.
Chemical Science
|March 19, 2019
Summary
A new radical aromatic amination reaction yields unprotected anilines, expanding substrate scope. Hydrogen bonding in hexafluoroisopropanol solvent enhances reactivity for direct C-H functionalization.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Direct C-H functionalization offers efficient synthetic routes.
- Radical aromatic amination is a key transformation for aniline synthesis.
- Existing methods often require protecting groups or have limited substrate scope.
Purpose of the Study:
- To develop a direct radical aromatic amination reaction.
- To improve the substrate scope of aniline synthesis via radical amination.
- To elucidate the role of solvent effects in enhancing reactivity.
Main Methods:
- Employing a novel radical aromatic amination protocol.
- Utilizing hexafluoroisopropanol as a key solvent.
- Investigating reaction mechanisms through mechanistic studies.
Main Results:
- Achieved direct synthesis of unprotected anilines.
- Demonstrated a significantly improved substrate scope compared to previous methods.
- Identified hydrogen bonding interactions as crucial for enhanced reactivity.
Conclusions:
- The developed radical amination reaction provides a versatile route to anilines.
- Solvent-mediated hydrogen bonding is a key factor in enhancing radical addition to arenes.
- This methodology offers potential for broader applications in direct C-H functionalization.
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