Choi Geunho, Hong Soon Hyeok
Department of Chemistry, College of Natural Science, Seoul National University, 1 Gwanak-ro, Seoul, 08826, South Korea.
Angew Chem Int Ed Engl. 2018 May 22;57(21):6166-6170. doi: 10.1002/anie.201801524. Epub 2018 Apr 25.
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
N-单甲基官能团是多种合成化合物和天然化合物中的常见结构单元。然而，由于过度甲基化导致的选择性问题，在有机合成中便捷地获得此类化合物仍然是一个基本挑战。为了解决这个问题，我们开发了一种方法，使用甲醇作为甲基化试剂，对各种结构和功能多样的胺进行选择性催化单甲基化，甲醇是一种可持续的化学原料。通过在氢气压力下于适当温度使用一种易于获得的钌催化剂，实现了脂肪族胺单甲基化的动力学控制。包括生物相关分子和药物在内的各种底物都被选择性地单甲基化，证明了所开发方法的通用性。
