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Remote Functionalization of α,β-Unsaturated Carbonyls by Multimetallic Sequential Catalysis
Ciro Romano1, Daniele Fiorito1, Clément Mazet1
1Department of Organic Chemistry , University of Geneva , 30 quai Ernest Ansermet , 1211 Geneva , Switzerland.
Journal of the American Chemical Society
|October 8, 2019
Summary
This study introduces novel multimetallic catalytic systems for remote functionalization of unsaturated carbonyls. These systems enable efficient synthesis of complex molecules through sequential reactions like isomerization and borylation.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Remote functionalization of α,β-unsaturated carbonyls remains a synthetic challenge.
- Developing efficient catalytic systems for sequential transformations is crucial for complex molecule synthesis.
Purpose of the Study:
- To develop novel multimetallic sequential catalytic systems for the remote functionalization of α,β-unsaturated carbonyls.
- To achieve difunctionalization and access complex molecular architectures not accessible by single catalyst systems.
Main Methods:
- Hydrometalation using palladium-hydride (Pd-H) or ruthenium-hydride (Ru-H) isomerization catalysts.
- Sequential catalysis combining palladium-catalyzed deconjugative isomerization with copper-catalyzed β-borylation.
- Utilizing [Pd/Cu] systems for enantioselective α-hydroboration and α-hydroamination.
- Integrating isomerization with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples for simultaneous difunctionalization.
Main Results:
- Successful remote functionalization of α,β-unsaturated carbonyls using multimetallic systems.
- Generation of thermodynamically stable 1,2-vinyl arenes as key intermediates.
- Access to a range of products through combined Pd/Cu catalysis, including β-borylated styrenyl derivatives.
- Achieved highly enantioselective α-hydroboration and α-hydroamination.
- Simultaneous difunctionalization at benzylic and homobenzylic positions via isomerization and SAD.
- Synthesis of a naturally occurring γ-butyrolactone with high yield and selectivity through an isomerization/dihydroxylation/lactonization sequence.
Conclusions:
- Multimetallic sequential catalysis offers a powerful strategy for the remote functionalization of α,β-unsaturated carbonyls.
- The developed methods provide access to valuable synthetic intermediates and complex molecular structures.
- The catalytic systems demonstrate high efficiency, selectivity, and broad applicability in organic synthesis.
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