Tan Fang-Fang, Li Zhan-Chao
School of Chemistry and Materials, Weinan Normal University, Weinan, China.
Sustainable Materials and Chemistry, Department of Wood Technology and Wood-based Composites, University of Göttingen, Göttingen, Germany.
Front Chem. 2025 May 14;13:1602003. doi: 10.3389/fchem.2025.1602003. eCollection 2025.
Trifluoromethylation stands as a pivotal technology in modern synthetic chemistry, playing an indispensable role in drug design, functional material development, and agrochemical innovation. With the growing emphasis on green chemistry principles, the pursuit of environmentally benign trifluoromethylation strategies has emerged as a critical research frontier. Trifluoroacetic acid (TFA), characterized by its cost-effectiveness, stability, and low toxicity, has become a promising alternative to conventional trifluoromethylation reagents. This review systematically summarizes advancements in photocatalytic decarboxylative trifluoromethylation using TFA and its derivatives over the past decade, focusing on three key activation mechanisms: single-electron transfer (SET), electron donor-acceptor (EDA) complex-mediated pathways, and ligand-to-metal charge transfer (LMCT). This paradigm shift is driven by the intrinsic limitations of conventional thermal decarboxylation, particularly its reliance on harsh conditions and significant environmental burdens. In contrast, photocatalytic strategies enable efficient C-CF bond construction under mild conditions, offering a modular platform for synthesizing fluorinated functional molecules. Strategic research priorities should focus on overcoming fundamental challenges, including but not limited to optimizing photosensitizer catalytic efficiency, establishing regioselective manipulation strategies, and engineering multicomponent tandem reaction systems to achieve trifluoromethylation methodologies under mild conditions. Furthermore, the integration of mechanistic investigations with artificial intelligence-driven reaction prediction will accelerate the advancement of precision trifluoromethylation technologies. This progress is anticipated to provide sustainable synthetic solutions for next-generation fluorinated pharmaceuticals and advanced functional materials, effectively bridging the innovation gap between academic research and industrial implementation.
三氟甲基化是现代合成化学中的一项关键技术，在药物设计、功能材料开发和农用化学品创新中发挥着不可或缺的作用。随着对绿色化学原则的日益重视，寻求环境友好的三氟甲基化策略已成为一个关键的研究前沿。三氟乙酸（TFA）具有成本效益高、稳定性好和毒性低的特点，已成为传统三氟甲基化试剂的一个有前途的替代品。本文综述系统总结了过去十年中使用TFA及其衍生物的光催化脱羧三氟甲基化的进展，重点关注三种关键的活化机制：单电子转移（SET）、电子供体-受体（EDA）络合物介导的途径和配体到金属的电荷转移（LMCT）。这种范式转变是由传统热脱羧的固有局限性驱动的，特别是其对苛刻条件的依赖和重大的环境负担。相比之下，光催化策略能够在温和条件下实现高效的C-CF键构建，为合成氟化功能分子提供了一个模块化平台。战略研究重点应集中在克服基本挑战上，包括但不限于优化光敏剂催化效率、建立区域选择性操纵策略以及设计多组分串联反应系统以在温和条件下实现三氟甲基化方法。此外，将机理研究与人工智能驱动的反应预测相结合将加速精确三氟甲基化技术的发展。预计这一进展将为下一代氟化药物和先进功能材料提供可持续的合成解决方案，有效弥合学术研究与工业应用之间的创新差距。
