Li Qian-Yu, He Yuhang, Lin Yu-Mei, Gong Lei
Key Laboratory of Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China.
Innovation Laboratory for Sciences and, Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen, Fujian, 361005, China.
Chemistry. 2023 Dec 22;29(72):e202302542. doi: 10.1002/chem.202302542. Epub 2023 Nov 10.
Direct C-H methylation is a highly valuable approach for introducing methyl groups into organic molecules, particularly in pharmaceutical chemistry. Among the various methodologies available, photo-induced methylation stands out as an exceptional choice due to its mild reaction conditions, energy efficiency, and compatibility with functional groups. This article offers a comprehensive review of photochemical strategies employed for the direct and selective methylation of C(sp )-H, C(sp )-H, and C(sp)-H bonds in various organic molecules. The discussed methodologies encompass transition-metal-based photocatalysis, organophotocatalysis, as well as other metal-free approaches, including electron donor-acceptor (EDA)-enabled transformations. Importantly, a wide range of easily accessible agents such as tert-butyl peroxide, methanol, DMSO, methyl tert-butyl ether, TsOMe, N-(acetoxy)phthalimide, acetic acid, methyl halides, and even methane can serve as effective methylating reagents for modifying diverse targets. These advancements in photochemical C-H methylation are anticipated to drive further progress in the fields of organic synthesis, photocatalysis, and pharmaceutical development, opening up exciting avenues for creating novel organic molecules and discovering new drug compounds.
直接C-H甲基化是一种将甲基引入有机分子的极具价值的方法,尤其是在药物化学领域。在现有的各种方法中,光诱导甲基化因其温和的反应条件、能源效率以及与官能团的兼容性而成为一种卓越的选择。本文全面综述了用于各种有机分子中C(sp³)-H、C(sp²)-H和C(sp)-H键直接和选择性甲基化的光化学策略。所讨论的方法包括基于过渡金属的光催化、有机光催化以及其他无金属方法,包括电子供体-受体(EDA)驱动的转化。重要的是,多种易于获得的试剂,如叔丁基过氧化物、甲醇、二甲基亚砜、甲基叔丁基醚、对甲苯磺酸甲酯、N-(乙酰氧基)邻苯二甲酰亚胺、乙酸、卤代甲烷,甚至甲烷,都可以作为有效的甲基化试剂来修饰各种目标。光化学C-H甲基化的这些进展有望推动有机合成、光催化和药物开发领域的进一步发展,为创造新型有机分子和发现新的药物化合物开辟令人兴奋的途径。