Chemoselective and Stereoselective Alcoholysis of Binaphthyl Phosphonothioates: Straightforward Access to Both Stereoisomers of Biologically Relevant P-Stereogenic Phosphonothioates
Chemoselective and Stereoselective Alcoholysis of Binaphthyl Phosphonothioates: Straightforward Access to Both Stereoisomers of Biologically Relevant P-Stereogenic Phosphonothioates
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DOI：
10.1021/acs.joc.0c00687
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发表时间：
2020-11-20
影响因子：
3.6
通讯作者：
Murai, Toshiaki
中科院分区：
文献类型：
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作者：
Kuwabara, Kazuma;Maekawa, Yuuki;Murai, Toshiaki
P-立体异构硫代磷酸酯由于其作为磷酸和硫代磷酸酯类似物的有效生物活性而引起了极大的关注。我们在这里展示了通过使用联萘硫代膦酸酯作为手性模板直接获得 P-立体异构硫代膦酸酯。联萘硫代膦酸的第一步醇解是通过将联萘基的轴向手性转移到磷原子的中心手性来进行的，仅得到具有中等至优异的非对映选择性的一元醇加合物。所得产物在少量过量的醇和碱存在下进一步醇解，完全消除联萘基，得到具有高对映体过量的相应的P-立体异构硫代膦酸酯。对第一步醇解反应机理的 DFT 研究表明，硫原子与钠阳离子的配位是控制非对映选择性的关键因素。该方法可用于制备高非对映体纯度的 G6P 类似物的两种立体异构体。
P-Stereogenic phosphonothioates have attracted great attention due to their potent biological activities as analogues of phosphoric acids and phosphorothioates. We demonstrate here straightforward access to P-stereogenic phosphonothioates through the use of binaphthyl phosphonothioates as a chiral template. The first-step alcoholysis of binaphthyl phosphonothioates proceeded via a transfer of the axial chirality of a binaphthyl group to the central chirality of a phosphorus atom to give only monoalcohol adducts with moderate to excellent diastereoselectivities. Further alcoholysis of the obtained products in the presence of a small excess of alcohol and base proceeded with complete elimination of a binaphthyl group to give the corresponding P-stereogenic phosphonothioates with high enantiomeric excess. A DFT study of the reaction mechanisms in first-step alcoholysis indicated that the coordination of a sulfur atom to a sodium cation is the key factor in controlling the diastereoselectivities. This method can be applied to prepare both stereoisomers of a G6P analogue with high diastereomeric purity.