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Palladium-catalyzed alpha-arylation of esters
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Journal of the American Chemical Society
|August 17, 2001
Summary
A novel one-pot palladium-catalyzed method enables alpha-arylation of esters using aryl bromides and chlorides. This efficient synthesis yields important drug derivatives and creates quaternary carbon centers.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Palladium-catalyzed cross-coupling reactions are crucial in organic synthesis.
- Efficient methods for alpha-arylation of esters are highly sought after for constructing complex molecules.
Purpose of the Study:
- To develop a simple and efficient one-pot procedure for the palladium-catalyzed intermolecular alpha-arylation of esters.
- To explore the scope and limitations of the developed method for synthesizing valuable compounds.
Main Methods:
- Utilized palladium acetate (Pd(OAc)2) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) as catalysts.
- Employed bulky electron-rich o-biphenyl phosphines as ligands.
- Used lithium bis(trimethylsilyl)amide (LiHMDS) as the base for the reaction.
Main Results:
- Achieved high yields and selectivities for monoarylation of various esters with aryl bromides at room temperature or 80°C.
- Successfully synthesized tert-butyl esters of naproxen (79% yield) and flurbiprofen (86% yield).
- Demonstrated the catalyst system's activity with aryl chlorides and the formation of quaternary centers using trisubstituted ester enolates.
Conclusions:
- The developed one-pot procedure offers a simple and effective route for alpha-arylation of esters.
- The method provides access to important nonsteroidal anti-inflammatory drug derivatives and complex molecular architectures.
- The catalytic system shows broad applicability, including the use of aryl chlorides and the synthesis of sterically hindered compounds.
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