Catalytic Asymmetric Synthesis of Aminophosphonic Acids Directed toward Peptide Mimetics

针对肽模拟物的氨基膦酸的催化不对称合成

• 批准号: 08672413
• 负责人: SASAI Hiroaki
• 金额: $ 1.6万
• 依托单位: Osaka University (1997)The University of Tokyo (1996)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672413/
• 关键词: Ytterbium; Rare Earth; Asymmetric Catalyst; Aminophosphonic Acid; Imine; Dimethyl Phosphite; Heterobimetallic; Multifubctional Catalyst; 触媒的不斉合成; ヒドロホスホニル化

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.

首次实现了环亚胺的催化和对映选择性氢膦化反应。此外，我们还发现了一种新的高效的不对称方法，使用噻唑啉作为亚胺模型组分来合成环氨基膦酸盐。通过杂双金属(R)- lnpb催化（Ln=类镧金属，P=钾，B=(R)=联萘酚）C=N双键的氢膦化反应可合成具有理想药理意义的膦酸盐，对映体过量可达98%，化学产率可达98%。详细研究了对映选择性和化学产率分别与一系列反应参数（如类镧和碱金属、溶剂、反应温度、压力和催化量）的关系。优选出一种催化镧系体系“(R)-YbPB(5 mol %) / 50 C / 48 h / thf -甲苯（1:7）”。对催化活性配合物进行了分离和光谱分析。此外，进行了^<32>P和^1H NMR谱和LDI-TOF质谱研究，以支持该(R)- lnpb络合物催化的氢膦化反应的假设机制过程。

项目成果

Harald Groger: "First Catalytic Asymmetric Hydrophosphonylation of Cyclic Imines : Highly Efficient Enantioselective Approach to a 4-Thiazolidinylphosphonate via Chiral Titanium and Lanthanoid Catalysts" Tetrahedron Lett.37. 9291-9292 (1996)

Harald Groger：“环状亚胺的首次催化不对称氢膦酰化：通过手性钛和镧系催化剂实现 4-噻唑烷基膦酸酯的高效对映选择性方法”Tetrahedron Lett.37。

Harald Groger: "First Catalytic Asymmetric Hydrophosphonylation of Cyclic Imines : Highly Efficient Enantioselective Approach to a 4-Thiazolidinyl-phosphonate via Chiral Titanium and Lanthanoid Catalysts" Tetrahedron Lett.37. 9291-9292 (1996)

Harald Groger：“环状亚胺的首次催化不对称氢膦酰化：通过手性钛和镧系催化剂实现 4-噻唑烷基膦酸酯的高效对映选择性方法”Tetrahedron Lett.37。

Harald Groger: "A New and Highly Efficient Asymmetric Route to Cyclic alpha-Amino Phosphonates : The first Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid Complexes" J.Am.Chem.Soc.120 in pre

Harald Groger：“环状 α-氨基磷酸盐的新型高效不对称路线：手性异双金属镧系络合物催化的环状亚胺的第一个催化对映选择性氢膦酰化”J.Am.Chem.Soc.120 预刊

Harald Groger: "First Catalytic Asymmetric Hydrophosphonylation of Cyclic Imines : Highly Efficient Enantioselective Approach to a 4 Thiazolidinylphosphonate via Chiral Titanium and Lanthanoid Catalysts" Tetrahedron Lett.37. 9291-9292 (1996)

Harald Groger：“环状亚胺的首次催化不对称氢膦酰化：通过手性钛和镧系催化剂实现 4 噻唑烷基膦酸酯的高效对映选择性方法”Tetrahedron Lett.37。

Harald Groger: "First Catalytic Asymmetric Hydrophosphonylation of Cyclic Imines:Highly Efficient Enantioselective Approach to a 4-Thiazolidinylphosphonate via Chiral Titanium and Lanthanoid Catalysts" Tetrahedron Lett.37. 9291-9292 (1996)

Harald Groger：“环状亚胺的首次催化不对称氢膦酰化：通过手性钛和镧系催化剂实现 4-噻唑烷基膦酸酯的高效对映选择性方法”Tetrahedron Lett.37。