At Long Last: Olefin Metathesis Macrocyclization at High Concentration

Area of Science:

• Organic Chemistry
• Catalysis
• Macromolecular Science

Background:

• Ring-closing metathesis (RCM) is a powerful tool for macrocycle synthesis.
• Traditional RCM often requires high dilution conditions and large volumes of organic solvents.
• Achieving high yields and selectivity in RCM can be challenging for certain substrates.

Purpose of the Study:

• To develop a more efficient and environmentally friendly method for synthesizing macrocyclic compounds.
• To overcome limitations of classical RCM, particularly for challenging substrates.
• To explore the use of high-concentration conditions in metathesis reactions.

Main Methods:

• Utilized tailored ruthenium catalysts for High-Concentration Ring-Closing Metathesis (HC-RCM).
• Applied vacuum distillation to remove the macrocyclic product as it formed.
• Employed inexpensive, nonvolatile diluents instead of large quantities of organic solvents.
• Leveraged moisture and air-stable ruthenium catalysts, eliminating the need for protective atmospheres.

Main Results:

• Achieved high yields and selectivity in the synthesis of macrocyclic lactones, ketones, and ethers.
• Operated at concentrations 40 to 380 times higher than typical RCM conditions.
• Demonstrated successful synthesis of cyclic compounds previously considered unobtainable via RCM.
• Significantly reduced organic solvent usage compared to classical RCM.

Conclusions:

• High-Concentration Ring-Closing Metathesis (HC-RCM) provides a superior method for macrocyclization.
• The HC-RCM method offers enhanced efficiency, selectivity, and sustainability.
• This approach broadens the scope of accessible macrocyclic structures through metathesis.