Catalytic Asymmetric Synthesis of Aminophosphonic Acids Directed toward Peptide Mimetics

• Project/Area Number: 08672413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Osaka University (1997); The University of Tokyo (1996)
• Principal Investigator: SASAI Hiroaki Osaka University, Institute of Scientific and Industrial Research, Professor, 産業科学研究所, 教授 (90205831)
• Co-Investigator(Kenkyū-buntansha): 荒井 孝義 東京大学, 薬学部, 助手 (80272483)
• Project Period (FY): 1996 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Harald Groger: "A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates : The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid Complexes" J.Am.Chem.Soc.120(in press). (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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 press. (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
• [Publications] Harald Groger: "A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates : The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid Complexes" J.Am.Chem.Soc.120(in press). (1998)
• [Publications] 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)