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Bimolecular Coupling Reactions through Oxidatively Generated Aromatic Cations: Scope and Stereocontrol
Yubo Cui1, Louis A Villafane, Dane J Clausen
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, Telephone: (+1)412-62408727.
Tetrahedron
|August 6, 2013
Summary
New oxidative coupling reactions rapidly create diverse heterocyclic compounds. Using a chiral Brønsted acid enables stereoselective synthesis of enantiomerically enriched products via chiral electrophile generation.
Area of Science:
- Organic Chemistry
- Heterocyclic Chemistry
- Asymmetric Synthesis
Background:
- Chromenes, isochromenes, and benzoxathioles are key heterocyclic scaffolds.
- Accessing diverse, functionalized heterocycles remains a synthetic challenge.
- Stereoselective methods for generating chiral electrophiles are limited.
Purpose of the Study:
- To develop novel oxidative fragment coupling reactions for heterocycle synthesis.
- To investigate the stereoselective potential of these reactions using chiral catalysts.
- To achieve enantioselective synthesis of valuable heterocyclic compounds.
Main Methods:
- Reaction of chromenes, isochromenes, and benzoxathioles with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).
- Generation of stable aromatic cations followed by nucleophilic addition.
- Employing chiral Brønsted acids to induce asymmetry in the ion pair intermediate.
Main Results:
- Stable aromatic cations were successfully generated from the starting heterocycles.
- A range of structurally diverse heterocycles were rapidly synthesized via oxidative coupling.
- Enantiomerically enriched products were obtained when using a chiral Brønsted acid, demonstrating stereoselectivity.
- The stereoselectivity arises from the in situ generation of a chiral electrophile through oxidative C-H bond cleavage.
Conclusions:
- Oxidative fragment coupling offers a versatile route to complex heterocycles.
- The methodology allows for stereoselective synthesis, providing access to enantiomerically enriched compounds.
- This work presents a rare example of stereoselective synthesis driven by a chiral electrophile generated via C-H activation.
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