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New Approach to the Highly Stereoselective Horner-Wadsworth-Emmons Reaction Utilizing Lewis acids

Research Project

Project/Area Number 11672104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

SANO Shigeki  The University of Tokushima, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20226038)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsWittig reaction / Horner-Wadsworth-Emmons reaction / Lewis acid / fluorine / asymmetric synthesis / center of chirality / axis of chirality / α, β-unsaturated ester / 四置換オレフィン
Research Abstract

The Horner-Wadsworth-Emmons (HWE) reaction is one of the most efficient methods for the preparation of α, β-unsaturated esters, which play an important role in the synthesis of biologically active compounds. The reactions of aldehydes with phosphonates bearing α-substituents that stabilize the carbanion preferentially furnish the corresponding E-alkenes. However, the stereoselectivity of the HWE reactions with ketones has never been investigated in detail because of their low reactivity and low stereoselectivity. The conventional HWE reactions of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of sodium hydride gave the corresponding α, β-unsaturated esters with the modest E-selectivity. On the other hand, treatment of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of Sn(OSO_2CF_3)_2 and N-ethylpiperidine afforded α, β-unsaturated esters in a highly Z-selective fashion. A significant improvement in the selectivity and yield was found when the Still's reagent, methyl bis (trifluoroethyl) phosphonoacetate, was used under the Sn (II)-mediated conditions. On the basis of the experimental results, the high Z-selectivity in the Sn (II)-mediated HWE reactions of aryl alkyl ketones with these phosphonates can be rationalized in terms of six-membered transition state involving Sn (II) chelation. Similarly, excellent E-selectivity was observed in the HWE reactions of ethyl 2-fluoro-2-diethylphosphonoacetate with aryl alkyl ketones using Sn (OSO_2CF_3)_2 and N-ethylpiperidine. In addition, the Sn (II)-mediated asymmetric HWE reactions of isopropyl 2-fluoro-2-diethylphosphonoacetate with 4-substituted-cyclohexanones and 2-substituted-1,3-dioxan-5-ones in the presence of a chiral diamine afforded α, β-unsaturated esters with enantioselectivities of up to 80% ee.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] 佐野茂樹: "ヘテロ原子の特性を活用する高立体選択的反応の開発-HWE反応の新展開-"YAKUGAKU ZASSHI. 120・5. 432-444 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeki Sano: "Development of Highly Stereoselective Reactions Utilizing Heteroatoms-New Approach to the Stereoselective Horner-Wadsworth-Emmons Reaction-"YAKUGAKU ZASSHI. 120-5. 432-444 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐野茂樹: "ヘテロ原子の特性を活用する高立体選択的反応の開発-HWE反応の新展開-"YAKUGAKU ZASSHI. 120・5. 432-444 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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