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A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
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Selective α-Methylation of Ketones
Andriy I Frolov1,2, Eugeniy N Ostapchuk1,2, Alexander E Pashenko1,2
1Enamine Ltd, 78 Chervonotkatska str., Kyiv 02094, Ukraine.
The Journal of Organic Chemistry
|May 27, 2021
Summary
A new two-step method efficiently prepares α-methyl ketones via enaminone intermediates. This scalable process offers regioselective and diastereoselective hydrogenation, useful for building blocks and late-stage functionalization.
Area of Science:
- Organic Chemistry
- Synthetic Methodology
- Catalysis
Background:
- α-Methyl ketones are valuable synthetic intermediates.
- Existing methods for α-methylation often lack scalability or functional group tolerance.
Purpose of the Study:
- To develop a convenient, scalable, and robust two-step protocol for α-methylation of ketones.
- To optimize regioselective and diastereoselective hydrogenation of enaminones to α-methyl ketones.
Main Methods:
- Regioselective synthesis of enaminone intermediates from ketones.
- Diastereoselective and functional group tolerant hydrogenation of enaminones.
- Optimization of reaction conditions, including the role of acetone as a potential additive.
Main Results:
- Successful two-step α-methylation of various ketones.
- High regioselectivity in enaminone formation and diastereoselectivity in hydrogenation.
- Demonstrated scalability up to 100 g for several α-methyl ketone syntheses.
- Identified potential role of acetone in the hydrogenation step.
Conclusions:
- The developed method provides a convenient and scalable approach for α-methylation of ketones.
- The methodology is suitable for both early building block synthesis and late-stage CH-functionalization.
- The protocol exhibits advantages in terms of scope, functional group tolerance, and scalability compared to existing procedures.
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