Thiol-Yne click chemistry of acetylene-enabled macrocyclization

Area of Science:

• Organic chemistry
• Supramolecular chemistry
• Catalysis

Background:

• Macrocycles are crucial in chemical, material, and biological research.
• Efficient synthesis of macrocycles is challenging due to entropic penalties in ring formation.

Purpose of the Study:

• To develop an efficient method for synthesizing diverse sulfur-containing macrocycles.
• To explore the use of acetylene as a simple feedstock for macrocycle synthesis.

Main Methods:

• A novel photocatalyzed thiol-yne click reaction was employed.
• Visible light mediation facilitated a radical-polar crossover dihydrothiolation process.
• The reaction was applied to synthesize macrocycles up to 35-membered rings and linear functionalized molecules.

Main Results:

• Diverse sulfur-containing macrocycles and linear molecules were successfully synthesized.
• The reaction demonstrated versatility by producing organometallic complexes, a bis-sulfoxide ligand, and the antibiotic Tiamulin.
• Acetylene was utilized as a cost-effective starting material.

Conclusions:

• The developed photocatalyzed reaction offers a practical and efficient route to complex sulfur-containing macrocycles.
• This method provides a valuable tool for synthesizing high-value compounds from simple feedstocks.
• The reaction's amenability to synthesizing biologically relevant molecules highlights its broad applicability.