Tinelli Roberto, Schupp Manuel, Klose Immo, Shaaban Saad, Maryasin Boris, González Leticia, Maulide Nuno
Institute of Organic Chemistry, University of Vienna Währinger Straße 38 1090 Vienna Austria
Vienna Doctoral School in Chemistry, University of Vienna Währinger Straße 42 1090 Vienna Austria.
Chem Sci. 2024 Sep 9;15(38):15751-6. doi: 10.1039/d4sc05049e.
The deployment of fluorinated functional groups has become a widespread tool in medicinal chemistry due to the impact of fluorine on lipophilicity and metabolic stability. Among these compounds, enantiopure secondary trifluoromethylcarbinols are recurrent features in bioactive compounds. Herein, we present a diastereoselective redox-neutral process allowing the stereospecific synthesis of 1,5-carboxamido-trifluoromethylcarbinols through the formal reduction of a trifluoromethylketone into a trifluoromethylcarbinol. A combined experimental and computational investigation unveiled a network of interconnected equilibria leading to a key hydride transfer event.
由于氟对亲脂性和代谢稳定性的影响，氟化官能团的引入已成为药物化学中一种广泛应用的工具。在这些化合物中，对映体纯的仲三氟甲基甲醇是生物活性化合物中的常见特征。在此，我们展示了一种非对映选择性氧化还原中性过程，该过程通过将三氟甲基酮形式上还原为三氟甲基甲醇，实现了1,5-羧酰胺基三氟甲基甲醇的立体选择性合成。结合实验和计算研究揭示了一个相互关联的平衡网络，该网络导致了关键的氢化物转移事件。
