Organocatalytic Enantioselective Continuous-Flow Cyclopropanation
Patricia Llanes1, Carles Rodríguez-Escrich1, Sonia Sayalero1
1Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology , Av. Països Catalans, 16, 43007 Tarragona, Spain.
Organic Letters
|December 17, 2016
Summary
Solid-supported diarylprolinol catalysts enable efficient enantioselective cyclopropanation. A developed flow process allows for extended reactions and direct use in subsequent Wittig reactions.
Area of Science:
- Organic Chemistry
- Catalysis
- Flow Chemistry
Background:
- Diarylprolinol catalysts are effective organocatalysts.
- Enantioselective cyclopropanation is a key synthetic transformation.
- Flow chemistry offers advantages for reaction scalability and control.
Purpose of the Study:
- To develop solid-supported diarylprolinol catalysts for enantioselective cyclopropanation.
- To implement a continuous flow process for this reaction.
- To demonstrate the utility of the flow system in a telescoped process.
Main Methods:
- Preparation of six solid-supported diarylprolinol catalysts with varied anchoring and supports.
- Application of catalysts in enantioselective cyclopropanation reactions under flow conditions.
- Sequential flow experiments for library generation and telescoped Wittig reaction.
Main Results:
- Successful preparation and application of solid-supported diarylprolinol catalysts.
- Demonstration of a 48-hour continuous flow experiment.
- Generation of a library of 12 cyclopropanes.
- Direct utilization of the flow stream in a subsequent Wittig reaction.
Conclusions:
- Solid-supported diarylprolinol catalysts are effective for enantioselective cyclopropanation in flow.
- The developed flow method allows for long-term operation and library synthesis.
- Telescoping the cyclopropanation with a Wittig reaction showcases the method's practicality.
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