A Bioinspired C–O/C–X σ-Bond Metathesis

Abstract

Cross metathesis reactions of multiple bonds, such as alkenes and alkynes, have undoubtedly revolutionized various fields and become one of the most efficient strategies in organic synthesis. In contrast, metathesis reactions of more naturally abundant yet less reactive σ-bond bonds remain less developed, especially for polar C–X bonds, the existing activation modes are rather limited and reactions often occur between two C–X bonds of the same type. Here, inspired by the natural S-adenosylmethionine (SAM) cycle, we devise a σ-bond metathesis between the C–O bond of alcohols with various other different C–X bonds. This reaction is realized by using a delicate mixture of commonly used Lewis acids and allows fast access to various challenging thioethers or selenoethers from easily available ones by directly editing the C component of the C–X bond with easily available alcohols as the sources of the new C component. Like multiple bond metathesis, this method could also be rendered intramolecular to provide saturated heterocycles such as cyclic ethers, cyclic thioethers, 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–O/ C–X 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.