Practical Synthetic Reactions for Tine Chemical Using a Divalent Titanium Reagent

• Project/Area Number: 12450359
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: SATO Fumie Graduate Sch. of Biosci. & Biotech., Professor, 大学院・生命理工学研究科, 教授 (50016606)
• Co-Investigator(Kenkyū-buntansha): URABE Hirokazu Graduate Sch. of Biosci. & Biotech., Assoc. Professor, 大学院・生命理工学研究科, 助教授 (10176745) ; 岡本 専太郎 東京工業大学, 大学院・生命理工学研究科, 助手 (00201989)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥15,700,000 (Direct Cost: ¥15,700,000); Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000); Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000); Fiscal Year 2000: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: organotianium / acetylene / cyclization / vitamin D_3 / cyclohexane / benzene / divalent titanium / anymmetric synthesis / スルホニルアセチレン / レッペ反応 / シクロヒキセノン / 環化反応 / 3量化 / グリニャール反応剤

Research Abstract

A divalent titanium reagent developed by us which can be prepared from Ti (O-I-Pr)_4 and two equivalents of I-PrMgCl is non-toxic and inexpensive, and has versatile reactivity. The reagent therefore, has become widely used by many synthetic chemists.
Further study of the reactions using the reagent opens up new efficient synthetic methods mentioned below.
1) Practical synthetic method for preparing 1α, 25-dihydoxy-vitamin D_3 in which cyclization of bis-unsaturated compounds mediated by the reagent is a key reaction.
2) Synthetic method of chiral allyl and alleyl titanium reagent from optically active allyl and propargyl compounds, respectively, and their synthetic utilization.
3) Development of metalative Reppe reaction from internal and terminal acetylene and the reagent, which allows easy access to benzene and pyridine derivatives.
4) Practical method to prepare 1,4-diiodo-1,3-alkadienes and their utilization for synthesizing polysubstituted conjugated dynes and π-conjugated linear oligomers.

Research Products

• [Publications] Ryoichi Tanaka: "Selective Preparation of Benzyltitanium Compounds by the Metalative Reppe Reaction. Its Application to the First Synthesis of Alcyopterosin A"J.Am.Chem.Soc.. 124. 9682-9683 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Daisuke Suzuki: "Selective Syntheses of Metallated Pyridines from Two Different Unsymmetrical Acetylenes, a Nitrile, and a Titanium(II) Alkoxide"J.Am.Chem.Soc.. 124,14. 3518-3519 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ryota Nakajima: "Efficient and General Synthetic Approach to Pentasubstituted Conjugated Dienes Using Site-selective Coupling of Cuprates with 1,4-Diiodo-1,3-alkadienes as the Key Reaction"Angew.Chem.Int.Ed.Engl.. 41,16. 3023-3025 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Daisuke Suzuki: "Metalative Reppe Reaction. Organized Assembly of Acetylene Molecules on Titanium Template Leading to a New Style of Acetylene Cyclotrimerization"J.Am.Chem.Soc.. 123,32. 7925-7926 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sentaro Okamoto: "Ti(II)-Mediated Tandem Inter-and Intramolecular Coupling Reaction of Unsaturated Hydrocarbons : One-pot Preparation of Cyclopentanes and Cyclohexanes from Readily Available Acyclic Starting Materials"J.Am.Chem.Soc.. 123,20. 4857-4858 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sentaro Okamoto: "An Allyltitanium Derived from Acrolein 1,2-Dicyclohexylethylene Acetal and (η^2-propene)Ti(O-i-Pr)_2 as a Chiral Propionaldehyde Homoenolate Equivalent Which Reacts with Imines with Excellent Stereoselectivity. An Efficient and Practical Access to Optically Active γ-Amino Carbonyl Compounds"J.Am.Chem.Soc.. 123,15. 3462-3471 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ryouichi Tanaka: "Selective Preparation of Benzyltitanium Compounds by the Metalative Reppe Reaction. Its Application to the First Synthesis of Alycyopterosin A"J. Am. Chem. Soc.. 124. 9682-9683 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Daisuke Suzuki: "Selective Syntheses of Metallated Pyridine from Two Different Unsymmetrical Acetylenes, a Nitrile, and a Titanium(II) Alkoxide"J. Am. Chem. Soc.. 124, 14. 3518-3519 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ryota Nakajima: "Efficient and General Synthetic Approach to Pentasubstituted Conjugated Dienes Using Site-selective Coupling of Cuprates with 1,4-Diiodo-1,3-alkadienes as the Key Reaction"Angew. Chem. Int. Ed. Engl.. 41, 16. 3023-3025 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Daisuke Suzuki: "Metalative Reppe Reaction. Organized Assembly of Acetylene Molecules on Titanium Template Leading to a New Style of Acetylene Cyclotrimerization"J. Am. Chem. Soc.. 123, 32. 7925-7926 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sentaro Okamoto: "Ti(II)-Mediated Tandem Inter-and Intramolecular Coupling Reaction of Unsaturated Hydrocarbons: One-pot Preparation of Cyclopentanes and Cyclohexanes from Readily Available Acyclic Starting Materials"J. Am. Chem. Soc.. 123, 20. 4857-4858 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sentaro Okamoto: "An Allyltitanium Derived from Acrolein 1,2-Dicyclohexylethylene Acetal and (η^2-propene)Ti(O-I-Pr)_2 as a Chiral Propionaldehyde Homoenolate Equivalent Which Reacts with Imines with Excellent Stereoselectivity. An Efficient and Practical Access to Optically Active γ-Amino Carbonyl Compounds"J. Am. Chem. Soc.. 123, 15. 3462-3471 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yuuki Takayama: "Efficient and General Synthetic Method for Preparing Oligoenynes with Either trans-or cis-Olefinic Configuration"Organic Letters. 5,3. 365-368 (2003)
• [Publications] Ryoichi Tanaka: "Concise and Stereoselective Synthesis of Enamides and Dienamides by a Titanium-Mediated coupling Method"Organic Letters. 5,1. 67-70 (2003)
• [Publications] Miho Narita: "Sulfur-Functionalized Olefins for Titanacycle Formation : Tandem Asymmetric Cyclization and the Pummerer Reaction Based on Sulfoxides Promoted by Titanium(II)-to-Titaniumu(IV) Relay"Angew. Chem. Int. Ed. Engl.. 41,19. 3671-3674 (2002)
• [Publications] Ryoichi Tanaka: "Selective Preparation of Benzyltitanium Compounds by the Metalative Reppe Reaction. Its Application to the First Synthesis of Alcyopterosin A"J. Am. Chem. Soc.. 124. 9682-9683 (2002)
• [Publications] Daisuke Suzuki: "Selective Syntheses of Metallated Pyridines from Two Different Unsymmetrical Acetylenes, a Nitrile, and a Titanium(II) Alkoxide"J. Am. Chem. Soc.. 124,14. 3518-3519 (2002)
• [Publications] Ryota Nakajima: "Efficient and General Synthetic Approach to Pentasubstituted Conjugated Dienes Using Site-selective Coupling of Cuprates with 1,4-Diiodo-1,3-alkadienes as the Key Reaction"Angew. Chem. Int. Ed. Engl.. 41,16. 3023-3025 (2002)
• [Publications] Sentaro Okamoto: "Ti(II)-Mediated Tandem Inter- and Intramolecular Coupling Reaction of Unsaturated Hydrocarbons: One-pot Preparation of Cyclopentanes and Cyclohexanes from Readily Available Acyclic Starting Materials"J. Am. Chem. Soc.. 123,20. 4857-4858 (2001)
• [Publications] Takeshi Hanazawa: "Novel Synthetic Approach to 19-nor-1 α 25-Dihydroxyvitamin D_3 and Its Derivatives by Suzuki-Miyaura Coupling in Solution and on Solid Support"Organic Letters. 3,24. 3975-3977 (2001)
• [Publications] Daisuke Suzuki: "Metalative Reppe Reaction Organized Assembly of Acetylene Molecules on Titanium Template Leading to a New Style of Acetylene Cyclotrimerization"J. Am. Chem. Soc.. 123,32. 7925-7926 (2001)
• [Publications] Hirokazu Urabe: "Generation of Acetylene-Titanium Alkoxide Complex Preparation of (Z)-1, 2-Dideuterio-1-(trimethylsilyl)-1-hexene"Organic Syntheses. (in press).
• [Publications] Sentaro Okamoto: "Highly Stercocontrolled Synthesis of Carbacyclin from Acyclic Starting Materials via Ti(II)-Mediated Tandem Cyclization"J.Am.Chem.Soc.. 122,45. 11242-11243 (2000)
• [Publications] Takashi Hamada: "Expedient Construction of Multiple Stereogenic Centers in an Acyclic System via the Addition of Aldchydes, Kelones, and Chiral Imines to an Enyne-Titanium Alkoxide Complex"J.Am.Chem.Soc.. 122,29. 7138-7139 (2000)
• [Publications] Daisuke Suzuki: "Asymmetric Sythesis of Baylis-Hillman-Type Allyl Alcohols via a Chiral Acetylenic Ester-Titanium Alkoxide Complex"Angew.Chem.Int.Ed.Engl.. 39,18. 3290-3292 (2000)
• [Publications] Sentaro Okamoto: "One-pot Synthesis of a Variety of 1,4-Alkadienes and 1,2,4-Alkatrienes from Alkynes, Allyl, or Propargyl Compounds and Electrophiles by a (η^2-Propene)Ti(O-i-Pr)_2-Mediated Reaction"Synthesis(Special issue). 7. 975-979 (2000)
• [Publications] Hirokazu Urabe: "A Facile Preparation of exo-Cyclic Conjugated Dienes Fused to Lactams or Lactones via Intramolecular Coupling of Acetylenes and Their Behavior in Diels-Alder Reactions"Org.Lett.. 2,22. 3481-3484 (2000)
• [Publications] Takeshi Hanazawa: "Preparation of Titanated Alkoxyallenes from 3-Alkoxy-2-propyn-1-yl Carbonates and (η^2-Propene)Ti(O-i-Pr)_2 as an Efficient Ester Homoaldol Equivalent"Org.Lett.. 2,15. 2369-2371 (2000)