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One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates
Published on: January 15, 2018
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Carbonyl 1,2-transposition through triflate-mediated α-amination
Zhao Wu1, Xiaolong Xu1, Jianchun Wang1
1Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Science (New York, N.Y.)
|November 4, 2021
Summary
This study introduces a novel method to transpose ketones to adjacent carbons, creating unusual bioactive molecules. The protocol enables selective carbonyl migration for late-stage functionalization.
Area of Science:
- Organic Chemistry
- Synthetic Methodology
- Medicinal Chemistry
Background:
- Selective carbonyl oxygen migration within molecular scaffolds is synthetically challenging.
- Existing methods often lack efficiency or regioselectivity for adjacent carbon migration.
Purpose of the Study:
- To develop a straightforward protocol for the regioselective transposition of ketones to vicinal carbons.
- To enable late-stage functionalization for accessing novel bioactive analogs.
Main Methods:
- Conversion of ketones to alkenyl triflates.
- Palladium- and norbornene-catalyzed α-amination and ipso-hydrogenation using a bifunctional donor.
- Hydrolysis of the intermediate transposed enamine.
Main Results:
- A one- or two-pot protocol for 1,2-carbonyl migration was established.
- The method demonstrates regioselective transposition of the ketone functionality.
- Facilitates rapid synthesis of unusual bioactive analogs.
Conclusions:
- The developed method provides efficient access to 1,2-carbonyl-migrated products.
- This approach expands synthetic capabilities for drug discovery and analog generation.
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