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A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Alkyl-(Hetero)Aryl Bond Formation via Decarboxylative Cross-Coupling: A Systematic Analysis
Frederik Sandfort1, Matthew J O'Neill1, Josep Cornella1
1The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
Redox-active esters enable efficient cross-coupling of alkyl carboxylic acids with aryl and heteroaryl compounds. This breakthrough expands synthetic capabilities for forming crucial carbon-carbon bonds in chemical science.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Suzuki, Negishi, and Kumada couplings are vital for C-C bond formation, primarily between aromatic rings.
- The analogous coupling with alkyl halides is limited by the availability of suitable building blocks.
Purpose of the Study:
- To explore redox-active esters as versatile surrogates for alkyl halides in cross-coupling reactions.
- To identify optimal conditions and activating agents for coupling various alkyl carboxylic acids with organometallic species.
Main Methods:
- Systematic experimental design involving approximately 200 experiments.
- Utilizing readily accessible redox-active esters derived from carboxylic acids and amide coupling agents.
Main Results:
- Demonstrated successful cross-coupling of primary, secondary, and tertiary alkyl carboxylic acids.
- Facilitated the formation of C-C bonds with both aryl and heteroaryl organometallic species.
Conclusions:
- Redox-active esters provide a practical and efficient alternative to alkyl halides in cross-coupling.
- This methodology broadens the scope of C-C bond formation, impacting diverse areas of chemical science.
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