Sulfide Synthesis via A Bioinspired C-S σ-Bond Metathesis

Area of Science:

• Organic Chemistry
• Catalysis
• Bioinorganic Chemistry

Background:

• The S-adenosylmethionine (SAM) cycle is a crucial biological pathway.
• Traditional C-X bond forming reactions have limitations in scope and efficiency.
• Developing new catalytic methods for C-X bond functionalization is essential.

Purpose of the Study:

• To develop a novel mixed σ-bond metathesis reaction inspired by the natural SAM cycle.
• To enable direct editing of (sp³)-hybridized C-S bonds in organic sulfides.
• To expand the scope of σ-bond metathesis to include C-O and C-N bonds for heterocycle synthesis.

Main Methods:

• A mixed σ-bond metathesis reaction between organic sulfides and alcohols was devised.
• The reaction was catalyzed by a facile mixture of aluminum chloride (AlCl₃) and zinc iodide (ZnI₂).
• Mechanistic experiments and DFT calculations were employed to elucidate the reaction pathway.

Main Results:

• The developed method allows for the direct functionalization of (sp³)-hybridized C-S bonds in organic sulfides.
• The reaction provides fast access to various challenging organic sulfides.
• The methodology was successfully extended to intramolecular C-O and C-N bond metathesis, yielding saturated heterocycles like cyclic thioethers, ethers, and amines.

Conclusions:

• The bioinspired C-S/C-O metathesis reaction offers a powerful new tool in synthetic organic chemistry.
• This approach provides significant insights into σ-bond metathesis, drawing parallels with the natural SAM cycle.
• The methodology opens avenues for further advancements in synthesizing valuable organic molecules and heterocycles.