Catalytic Chemoselective O-Phosphorylation of Alcohols
Catalytic Chemoselective O-Phosphorylation of Alcohols
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DOI：
10.1021/acscentsci.9b01272
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发表时间：
2020-02-26
影响因子：
18.2
通讯作者：
Kanai, M.
中科院分区：
文献类型：
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作者：
Domon, K.;Puripat, M.;Kanai, M.
醇的磷酸化在生命科学和物理科学中都是一个非常重要的反应。产品磷酸单酯在生物体，天然产品，药品和有机材料中起着关键作用。然而，迄今为止合成磷酸单酯的大多数化学方法都需要多步骤序列，或者由于条件恶劣，可能仅限于特定类型的底物。因此，迫切需要一种能够从高度官能化前体醇简单生产磷酸盐单酯的替代方法。本文报道了用四丁基硫酸氢铵（TBAHS）和磷酸烯醇丙酮酸单钾盐（PEP-K）分别作为催化剂和磷酸基供体催化磷酸化具有高官能团耐受性的醇。该方法能够在多种醇底物（包括功能化小分子、碳水化合物和无保护肽）的羟基上直接引入非保护磷酸基团。核磁共振、质谱和密度泛函数理论分析表明，PEP-K和TBAHS产生了一种前所未有的混合酸酐，在该反应中充当了活性磷酰供体。这种操作简单和化学选择性的催化磷酸化允许高效生产密集功能化的o -磷酸化化合物，这些化合物在包括生物学和医学在内的各个领域都很有用。
Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living organisms, natural products, pharmaceuticals, and organic materials. Most of the chemical methods to date for synthesizing phosphate monoesters, however, require multistep sequences or are limited to specific types of substrates possibly due to harsh conditions. An alternative way to enable the simple production of phosphate monoesters from highly functionalized precursor alcohols is, thus, highly desired. We report herein a catalytic phosphorylation of alcohols with high functional group tolerance using tetrabutylammonium hydrogen sulfate (TBAHS) and phosphoenolpyruvic acid monopotassium salt (PEP-K) as the catalyst and phosphoryl donor, respectively. This method enables the direct introduction of a nonprotected phosphate group to the hydroxy group of a diverse menu of alcohol substrates, including functionalized small molecules, carbohydrates, and unprotected peptides. Nuclear magnetic resonance, mass spectrometric, and density functional theory analyses suggest that an unprecedented mixed anhydride species, generated from PEP-K and TBAHS, acts as an active phosphoryl donor in this reaction. This operationally simple and chemoselective catalytic phosphorylation allows for the efficient production of densely functionalized O-phosphorylated compounds, which are useful in diverse fields including biology and medicine.