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

Abstract In this manuscript, inspired by the natural S‐adenosylmethionine (SAM) cycle, we devised a mixed σ‐bond metathesis between the (sp 3 )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 AlCl 3 and ZnI 2 , which allows fast access to various challenging organic sulfides by directly editing the (sp 3 )C−S bond of easily available ones. Like multiple bond metathesis, this method could also be rendered intramolecular and extended to ether (sp 3 )C−O bond metathesis as well as amine (sp 3 )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.