Carbon isotope exchange mediated by vanadium complexes

项目摘要 拟议的研究重点是设计、合成和开发一系列钒- 通过=*CH2(*C=11C、13C和14C)基团转移进行碳同位素交换的基础催化剂 在末端烯烃之间。碳同位素交换是一个新兴的领域，它允许将碳- 14同位素直接进入目标化合物，用于代谢和药代动力学研究。此外， 将碳11集成到药物中是正电子发射断层扫描中不可或缺的工具。这个 本论文的创新之处在于在第一排基础上开发了烯烃复分解催化剂。 过渡金属，钒，利用高极化的V=C键。这些V烷基化合物的特征是 金属环丁烷的区域选择性形成，导致可逆的=CH2在 没有形成交叉产物和乙烯的末端烯烃，这得到了我们初步的支持 结果和DFT研究。因此，钒催化的碳同位素交换可以作为一种新的平台 将标记的碳原子引入广泛的药物和天然产品中，而不需要 开发新的多步骤综合策略。所提出的方法使用可访问的标签 碘甲烷(*CH3I)作为碳同位素源，可应用于含有各种 共同的官能团。该方法将扩展到含有烷基的生物活性分子，利用 串联脱氢/烯烃复分解策略。因此，碳同位素的第一个例子 将引入涉及甲基的交换。新概念、催化剂和 将通过应用于同位素标记的简明合成来强调协议 药品和天然产品。

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.