Diaryl ether and diaryl thioether syntheses on solid supports via copper (I)-mediated coupling.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Solid-Phase Synthesis

Background:

• Traditional synthesis of diaryl ethers and thioethers can be complex and low-yielding.
• Developing efficient solid-phase methods is crucial for combinatorial chemistry and drug discovery.

Purpose of the Study:

• To develop an efficient solid-phase synthesis for diaryl ethers and thioethers.
• To adapt solution-phase coupling conditions for solid-phase applications.
• To introduce a novel linker for diversity-oriented synthesis.

Main Methods:

• Immobilization of phenols or aryl halides onto a solid support.
• Copper-catalyzed coupling (CuCl, Cs(2)CO(3)) with aryl iodides/bromides or thiophenols/phenols in solution.
• Cleavage of synthesized compounds from the resin using saponification/transesterification or ozonolysis.

Main Results:

• Successful synthesis of diaryl ethers and thioethers on solid supports.
• Effective coupling of sterically hindered and electronically deactivated aryl moieties.
• High yields and purities of the target substances were achieved.
• A diversity-generating linker enabled multiple cleavage pathways.

Conclusions:

• The described method provides an efficient and versatile route to diaryl ethers and thioethers on solid supports.
• The developed linker facilitates diversity-oriented synthesis, expanding the utility of the method.
• This approach is suitable for generating libraries of compounds with potential applications in medicinal chemistry.