Project Summary The proposed studies focus on the design, synthesis, and development of a range of vanadium- based catalysts to perform carbon isotope exchange via =*CH2 (*C = 11C, 13C, and 14C) group transfer between terminal olefins. Carbon isotope exchange is an emerging area that allows incorporating carbon- 14 isotope directly into target compounds for metabolic and pharmacokinetic studies. Furthermore, the integration of carbon-11 into pharmaceuticals is an indispensable tool in positron emission tomography. The innovation of the proposed work is the development of olefin metathesis catalysts based on the first-row transition metal, vanadium, to take advantage highly polarized V=C bond. These V alkylidenes feature enabled regioselective formation of metallacyclobutane, resulting in reversible =CH2 transfer between terminal olefins without formation of cross-products and ethylene, which is supported by our preliminary results and DFT studies. Therefore, V-catalyze carbon isotope exchange can serve as a new platform to incorporate labeled carbon atoms into a wide range of pharmaceuticals and natural products without developing new multi-step synthetic strategies. The proposed approach uses accessible labeled iodomethane (*CH3I) as a carbon isotope source and can be applied to compounds containing various common functional groups. The method will be expanded to alkyl-containing bioactive molecules utilizing a tandem dehydrogenation/olefin metathesis strategy. Therefore, the first example of carbon isotope exchange involving the methyl group will be introduced. The utility of the new concepts, catalysts, and protocols will be emphasized through applications to the concise synthesis of isotopically labeled pharmaceuticals and natural products.