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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
A facilitated cyclic ether formation and its potential application in solid-phase peptide and organic synthesis
1Department of Chemistry, North Carolina State University, Raleigh 27695-8204, USA.
Chemical & Pharmaceutical Bulletin
|March 8, 2000
Summary
A novel trimethyl lock system enables efficient cyclic ether formation and carboxylic acid release. This base-mediated reaction proceeds in high yields under mild conditions, offering potential for new synthetic linkers.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- The "trimethyl lock" system is known to promote lactonization via stereopopulation control.
- Cyclic ether formation typically requires specific conditions and reagents.
Purpose of the Study:
- To investigate the utility of a trimethyl lock system for base-mediated cyclic ether formation.
- To explore the concomitant release of carboxylic acid during this process.
Main Methods:
- Synthesis of fifteen model compounds featuring the trimethyl lock system.
- Treatment of model compounds with anhydrous tetrabutylammonium fluoride (TBAF) under varying temperatures.
- Analysis of reaction products to confirm cyclic ether formation and carboxylate release.
Main Results:
- All fifteen synthesized model compounds successfully underwent base-mediated cyclic ether formation.
- High yields of cyclic ethers were achieved at temperatures ranging from 0°C to room temperature.
- The reaction consistently resulted in the release of the attached carboxylate.
Conclusions:
- The trimethyl lock system effectively facilitates base-mediated cyclic ether formation.
- This method offers a high-yielding and mild approach for synthesizing cyclic ethers with concomitant carboxylate release.
- The developed system shows potential for application as a two-dimensional linker in solid-phase synthesis.
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