Sulfide Synthesis via A Bioinspired C–S σ‐Bond Metathesis

In this manuscript, inspired by the natural S‐adenosylmethionine (SAM) cycle, we devised a mixed σ‐bond metathesis between the (sp3)C–S bond of organic sulfides with the C–O bond of alcohols. This reaction is mediated by a readily available and operationally facile mixture of AlCl3 and ZnI2, which allows fast access to various challenging organic sulfides by directly editing the (sp3)C–S bond of easily available ones. Like multiple bond metathesis, this method could also be rendered intramolecular and extended to ether (sp3)C–O bond metathesis as well as amine (sp3)C–N bond metathesis to provide saturated heterocycles such as cyclic thioethers, cyclic ethers, as well as cyclic amines. Mechanistic experiments and DFT calculations were carried out to show a high level of resemblance to the natural SAM cycle. We anticipate this bioinspired design of C–S/C–O metathesis will infuse the area of a σ‐bond metathesis with more insights and provide opportunities for further advances in areas that have been facilitated by traditional C–X bond forming reactions.