美国莱斯大学West, Julian G.团队报道了烯烃与羧酸的光催化氢氟烷基化。相关研究成果于2023年11月13日发表于国际顶尖学术期刊《自然—化学》。

在药物中掺入氟烷基基序可以增强母体分子的治疗特性。烯烃的氢氟烷基化已成为制备各种氟烷基化化合物的一种有前途的途径；然而，目前的方法需要超化学计量的氧化剂、昂贵/氧化的氟烷基化试剂和贵金属，并且通常表现出有限的范围，因此非常需要解决这些限制的通用方案。

该文中，研究人员报道了以廉价、丰富和可用的氟烷基羧酸为唯一试剂的烯烃的氢氟烷基化。三氟、二氟、单氟和全氟烷基化都得到了证明，具有广泛的范围、温和的条件（氧化还原中性）以及对生物活性分子进行后期修饰的潜力。成功的关键是通过利用地球丰富、廉价的铁和氧化还原活性硫醇催化，克服原料氟烷基羧酸（如三氟乙酸）极高的氧化还原潜力，使这些试剂能够在没有预活化的情况下直接用作氢全氟烷基化供体。初步的机制研究揭示了这种合作过程的根本性质。

附：英文原文

Title: Photocatalytic hydrofluoroalkylation of alkenes with carboxylic acids

Author: Bian, Kang-Jie, Lu, Yen-Chu, Nemoto, David, Kao, Shih-Chieh, Chen, Xiaowei, West, Julian G.

Issue&Volume: 2023-11-13

Abstract: Incorporation of fluoroalkyl motifs in pharmaceuticals can enhance the therapeutic profiles of the parent molecules. The hydrofluoroalkylation of alkenes has emerged as a promising route to diverse fluoroalkylated compounds; however, current methods require superstoichiometric oxidants, expensive/oxidative fluoroalkylating reagents and precious metals, and often exhibit limited scope, making a universal protocol that addresses these limitations highly desirable. Here we report the hydrofluoroalkylation of alkenes with cheap, abundant and available fluoroalkyl carboxylic acids as the sole reagents. Hydrotrifluoro-, difluoro-, monofluoro- and perfluoroalkylation are all demonstrated, with broad scope, mild conditions (redox neutral) and potential for late-stage modification of bioactive molecules. Critical to success is overcoming the exceedingly high redox potential of feedstock fluoroalkyl carboxylic acids such as trifluoroacetic acid by leveraging cooperative earth-abundant, inexpensive iron and redox-active thiol catalysis, enabling these reagents to be directly used as hydroperfluoroalkylation donors without pre-activation. Preliminary mechanistic studies support the radical nature of this cooperative process.

DOI: 10.1038/s41557-023-01365-0

Source: https://www.nature.com/articles/s41557-023-01365-0