Vanadium-Mediated Carbon Isotope Exchange of Terminal Alkenes

The incorporation of carbon isotopes into bioactive compounds is of great importance in chemistry, biology, and medicine. Especially valuable are catalytic procedures that rely on a limited collection of available labeled materials. Recently we introduced a conceptually novel solution to carbon isotope exchange (CIE) for terminal olefins based on the preference of V alkylidenes for degenerate metathesis. However, the previous report utilized a V catalyst that suffered from functional group tolerance due to the high electrophilicity of the V center, making it impractical for biological compounds. Herein, we utilized V catalysts containing electron-donating groups to overcome those challenges. We utilize isotopically labeled substituted styrene as a labeled ═¹³CH₂ moiety source, prepared from ¹³C-labeled iodomethane. The isotope source can be easily removed from the reaction mixture, recovered, and reused. A diverse range of terminal alkenes, including bioactive molecules, were tested to showcase the capabilities and limitations of the developed method.