Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, 001-0021, Japan.
Nat Commun. 2021 Feb 11;12(1):966. doi: 10.1038/s41467-020-20872-z.
Hydrogen atom transfer (HAT) hydrogenation has recently emerged as an indispensable method for the chemoselective reduction of unactivated alkenes. However, the hitherto reported systems basically require stoichiometric amounts of silanes and peroxides, which prevents wider applications, especially with respect to sustainability and safety concerns. Herein, we report a silane- and peroxide-free HAT hydrogenation using a combined cobalt/photoredox catalysis and ascorbic acid (vitamin C) as a sole stoichiometric reactant. A cobalt salophen complex is identified as the optimal cocatalyst for this environmentally benign HAT hydrogenation in aqueous media, which exhibits high functional-group tolerance. In addition to its applicability in the late-stage hydrogenation of amino-acid derivatives and drug molecules, this method offers unique advantage in direct transformation of unprotected sugar derivatives and allows the HAT hydrogenation of unprotected C-glycoside in higher yield compared to previously reported HAT hydrogenation protocols. The proposed mechanism is supported by experimental and theoretical studies.
氢原子转移（HAT）氢化最近已成为非活化烯烃的选择性还原的不可或缺的方法。然而，迄今为止报道的系统基本上需要化学计量的硅烷和过氧化物，这限制了其更广泛的应用，特别是在可持续性和安全性方面。在此，我们报告了一种无硅烷和过氧化物的 HAT 氢化，使用钴/光氧化还原催化和抗坏血酸（维生素 C）作为唯一的化学计量反应物。发现钴席夫碱配合物是在水相介质中进行这种环境友好的 HAT 氢化的最佳共催化剂，它对官能团具有高耐受性。除了在氨基酸衍生物和药物分子的后期氢化中的适用性外，该方法在未保护的糖衍生物的直接转化中具有独特的优势，并允许与以前报道的 HAT 氢化相比，以更高的产率进行未保护的 C-糖苷的 HAT 氢化。该提议的机制得到了实验和理论研究的支持。
