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.