A Base-Promoted Reductive Coupling Platform for the Divergent Defluorofunctionalization of Trifluoromethylarenes
Shawn E Wright1, Jeffrey S Bandar1
1Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
Journal of the American Chemical Society
|July 14, 2022
Summary
A new trifluoromethylarene reductive coupling method enables access to diverse difluorobenzylic substructures. This C-F bond functionalization strategy utilizes a Lewis base and disilane reagent for efficient synthesis of novel difluoroalkylarene scaffolds.
Area of Science:
- Organic Chemistry
- Fluorine Chemistry
- Synthetic Methodology
Background:
- Trifluoromethylarenes are important motifs in pharmaceuticals and materials.
- Efficient methods for difluorobenzylic substructure synthesis are limited.
- C-F bond functionalization offers a powerful route to novel chemical entities.
Purpose of the Study:
- To develop a novel reductive coupling method for trifluoromethylarenes.
- To expand the scope of accessible difluorobenzylic substructures.
- To establish a new C-F bond functionalization strategy.
Main Methods:
- Catalytic Lewis base-promoted reductive coupling of trifluoromethylarenes.
- Use of disilane reagents and formamide as solvent.
- Isolation and characterization of difluorobenzyl silane intermediates.
Main Results:
- A novel trifluoromethylarene reductive coupling method was established.
- The reaction selectively replaces one trifluoromethyl fluorine atom.
- Access to over 20 unique difluoroalkylarene scaffolds was achieved.
- A difluorobenzyl silane intermediate was identified and isolated.
Conclusions:
- The developed method significantly expands the synthetic utility of trifluoromethylarenes.
- This C-F bond functionalization approach provides rapid access to valuable difluoroalkylarene scaffolds.
- The methodology offers a new tool for constructing complex fluorinated organic molecules.
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