Organocatalytic Enantioselective Cycloetherifications Using a Cooperative Cation-Binding Catalyst

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry
• Catalysis

Background:

• Chiral cyclic ethers are important structural motifs in pharmaceuticals and natural products.
• Developing efficient and enantioselective synthetic methods for these compounds remains a significant challenge in organic synthesis.

Purpose of the Study:

• To develop a highly enantioselective cycloetherification strategy for synthesizing enantioenriched five-, six-, and seven-membered oxygen-containing heterocycles.
• To utilize Song's cation-binding oligoethylene glycol (oligoEG) catalyst for this transformation.

Main Methods:

• The study employed a cycloetherification reaction of various ε-, ζ-, and η-hydroxy-α,β-unsaturated ketones.
• Potassium fluoride (KF) was used as the base in conjunction with Song's chiral oligoEG catalyst.
• The reaction was performed under conditions designed to promote cooperative cation-binding catalysis within a chiral supramolecular cage.

Main Results:

• The developed strategy successfully synthesized enantioenriched tetrahydrofurans, tetrahydropyrans, and oxepanes with high enantiopurity.
• A wide range of substituted hydroxy-α,β-unsaturated ketones were effectively cyclized.
• The enantioselectivity was attributed to the formation of a densely confined chiral supramolecular cage.

Conclusions:

• A straightforward and highly enantioselective cycloetherification method for synthesizing chiral oxacycles has been established.
• The cooperative cation-binding catalysis facilitated by the chiral oligoEG catalyst is key to the reaction's success.
• This approach offers a valuable tool for accessing complex chiral heterocyclic compounds.