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Updated: Jan 8, 2026
08:12
A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
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Ring-Expansion of Ketones with [1.1.1]Propellane
Ganesh Arjun Kadam1, Suparnak Midya1, Vitalina Levchenko2,3
1Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India.
Journal of the American Chemical Society
|December 22, 2025
Summary
This study introduces a new method for ketone ring-expansion using [1.1.1]propellane. The practical and scalable reaction efficiently produces valuable spirocyclic compounds for synthesis and drug discovery.
Area of Science:
- Organic Chemistry
- Synthetic Methodology
- Medicinal Chemistry
Background:
- Spirocyclic scaffolds are crucial in drug discovery.
- Efficient synthesis of complex spirocycles remains a challenge.
Purpose of the Study:
- To develop a novel ring-expansion method for ketones.
- To enable the synthesis of diverse spirocyclic structures.
Main Methods:
- Electrophilic activation of [1.1.1]propellane.
- Reaction with a broad spectrum of ketones.
- Mechanistic studies using control experiments and DFT calculations.
Main Results:
- Successful ring-expansion of various ketones.
- Excellent functional group tolerance (esters, amides, amines).
- Scalable synthesis demonstrated up to 56 g.
- Preparation of mono-, bis-, and tris-spirocyclic scaffolds.
Conclusions:
- The developed method is practical and scalable.
- It provides access to valuable spirocyclic compounds.
- Mechanistic understanding was achieved through experimental and computational studies.
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