Methylene-bridged glycoluril dimers: synthetic methods

Area of Science:

• Supramolecular Chemistry
• Organic Synthesis

Background:

• Methylene-bridged glycoluril dimers are fundamental building blocks for cucurbiturils (CB[n]) and their derivatives.
• Efficient synthesis of these dimers is crucial for accessing diverse CB[n] macrocycles.

Purpose of the Study:

• To describe three complementary methods for synthesizing C- and S-shaped methylene-bridged glycoluril dimers.
• To explore the preparation of functionalized glycoluril derivatives for dimer synthesis.
• To investigate diastereoselective homodimerization and heterodimerization reactions.

Main Methods:

• Preparation of functionalized glycoluril derivatives (1a-d, 5a-f).
• Alkylation of glycoluril derivatives with bis(halomethyl)aromatics.
• Acid-catalyzed condensation reactions with paraformaldehyde for C- and S-shaped dimer formation.
• Diastereoselective dimerization of cyclic ethers and heterodimerization reactions.

Main Results:

• Successful synthesis of C- and S-shaped methylene-bridged glycoluril dimers in good to excellent yields.
• High diastereoselectivity observed in the formation of C-shaped dimers.
• Development of selective heterodimerization routes for challenging syntheses.
• X-ray structures of key dimers elucidated structural features.

Conclusions:

• Three effective methods for synthesizing C- and S-shaped methylene-bridged glycoluril dimers have been established.
• The synthetic strategies provide access to precursors for cucurbituril (CB[n]) synthesis.
• Understanding electronic requirements aids in optimizing CB[n] synthesis.