Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures

Area of Science:

• Organic Chemistry
• Catalysis
• Macromolecular Science

Background:

• Ring-closing metathesis (RCM) is crucial for synthesizing macrocycles used in pharmaceuticals and fragrances.
• Oligomerization is a common side reaction in RCM, reducing target yields.
• Existing ruthenium catalysts (Ru-NHC) can convert oligomers but suffer from decomposition, limiting efficiency.

Purpose of the Study:

• To develop novel ruthenium catalysts for efficient macrocyclization via RCM.
• To address catalyst decomposition and improve selectivity in RCM reactions.
• To investigate the role of hemilabile chelates in enhancing catalytic activity.

Main Methods:

• Synthesis of new ruthenium catalysts incorporating a hemilabile o-dianiline (ODA) chelate.
• Application of these catalysts in RCM reactions of various dienes.
• Analysis of reaction rates, yields, and selectivity, with a focus on macrocyclization versus oligomerization.

Main Results:

• The novel Ru-NHC-ODA catalysts significantly accelerate macrocyclization, especially for dienes with polar, hydrogen-bonding sites.
• These catalysts demonstrate improved stability, potentially inhibiting decomposition during metathesis.
• Fast macrocyclization of conformationally flexible dienes was achieved at room temperature, outperforming previous Ru-NHC systems.

Conclusions:

• Incorporating hemilabile ODA chelates into Ru-NHC catalysts enhances RCM efficiency for macrocycle synthesis.
• The new catalysts offer a promising solution to overcome oligomerization and catalyst decomposition issues.
• This work advances catalytic methods for producing valuable macrocyclic compounds.