Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations
Andrea Cataffo1,2, Miguel Peña-López1,2, Riccardo Pedrazzani1,2
1Institute of Chemical Research of Catalonia (ICIQ), CERCA, Barcelona Institute of Science and Technology, Av. Països Catalans 16, 43007, Tarragona, Spain.
Angewandte Chemie (International Ed. in English)
|October 24, 2023
Summary
This study introduces two novel stereoselective cyclization methods for synthesizing complex molecules. These methods utilize chiral auxiliaries and a gold catalyst to create enantioenriched spirocyclic ketones and β-tetralones.
Area of Science:
- Organic Chemistry
- Catalysis
- Asymmetric Synthesis
Background:
- Chiral auxiliaries are crucial for controlling stereochemistry in organic synthesis.
- Gold catalysis offers unique reactivity for cyclization reactions.
Purpose of the Study:
- To develop novel stereoselective cyclization strategies using chiral auxiliaries and gold catalysis.
- To synthesize enantioenriched spirocyclic ketones and β-tetralones.
Main Methods:
- Stereoselective cascade cyclization of 1,5-enynes using Oppolzer camphorsultam and [JohnPhosAu(MeCN)SbF6] catalyst.
- Stereoselective alkoxycyclization of 1,6-enynes mediated by an Evans-type oxazolidinone.
- One-pot cyclization-hydrolysis and reduction-hydrolysis sequences for auxiliary removal.
- Density Functional Theory (DFT) studies to elucidate stereoselectivity.
Main Results:
- Enantioenriched spirocyclic ketones were obtained via a one-pot cyclization-hydrolysis sequence.
- Enantioenriched β-tetralones were synthesized through a reduction-hydrolysis sequence.
- DFT studies confirmed steric clash dictates diastereoselective cyclization via the Si face.
Conclusions:
- The developed methods provide efficient access to enantioenriched cyclic compounds.
- Chiral auxiliary control is key to achieving high stereoselectivity in these gold-catalyzed cyclizations.
- The findings offer valuable synthetic routes for complex molecule construction.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
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