Catalytic Asymmetric Synthesis of Aminophosphonic Acids Directed toward Peptide Mimetics

首次实现了环亚胺的催化和不对称选择性氢膦酰化反应。此外，我们发现了一种新的和高效的不对称的方法，环氨基膦酸酯使用噻唑啉作为亚胺模型组件。通过杂环（R）-LnPB催化的（Ln=镧系金属，P=钾，B=（R）=联萘）C=N双键的氢膦酰化反应，可以合成所需的药学上感兴趣的膦酸酯，对映体过量高达98%，化学产率高达98%。详细研究了对映选择性和化学产率分别对一系列反应参数（例如，镧系元素和碱金属、溶剂、反应温度、压力和催化量）。优化了稀土催化体系“（R）-YbPB（5mol%）/ 50 ℃/ 48 h /THF-甲苯（1：7）”，并对催化活性配合物进行了分离和光谱分析。此外，进行了13 <32>P和131 H NMR光谱和LDI-TOF质谱研究以支持该（R）-LnPB-络合物催化的氢膦酰化反应的假定机理过程。

The catalytic and enantioselective hydrophosphonylation of cyclic imines has achieved for the first time. In addition, we have uncovered a new and highly efficient asymmetric approach to cyclic-amino phosphonates using thiazolines as the imine model component. The desired pharmaceutically interesting phosphonates could be synthesized by a heterobimetallic (R)-LnPB-catalyzed (Ln=lanthanoid metal, P=potassium, B=(R)=binaphthol) hydrophosphonylation of the C=N double bond with up to 98% enantiomeric excess and up to 98% chemical yield. A detailed investigation concerning the dependence of enantioselectivity and chemical yield, respectively, on a series of reaction parameters (e.g., lanthanoid and alkali metal, splvent, reaction temperature, pressure, and catalytic amount) is reported. An optimized catalytic lanthanoid system "(R)-YbPB(5 mol %) / 50ﾟC / 48 h / THF-toluene (1 : 7)" was found. The catalytically active complex was isolated and analyzed by spectroscopic methods. In addition, ^<32>P and ^1H NMR spectroscopic and LDI-TOF mass spectrometric investigations were carried out to support a postulated mechanistic course for this (R)-LnPB-complex-catalyzed hydrophosphonylation reaction.