| Project/Area Number |
09470482
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Research and Education Center for Materials Science, Nara Institute of Science and Technology (1998)
The University of Tokyo (1997) |
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Principal Investigator |
KOGA Kenji Professor, Graduate School of Pharmaceutical Sciences, University of Tokyo (1997) ; Professor, Research and Education Center for Materials Science, Nara Institute of Science and Technology (1998), 物質科学教育研究センター, 教授 (10012600)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Kazumasa Assistant, Graduate School of Pharmaceutical Sciences, University of Tokyo (1997, 大学院・薬学系研究科(平成9年度), 助手 (60282612)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Lithium Enolate / Catalytic Asymmetric Deprotonation / Catalytic Asymmetric Alkylation / Catalytic Asymmetric Protonation / Chiral Bidentate Lithium Amide / Chiral Tetradentate Amine / Lithium-Hydrogen Interchange / Lignad Exchange / 触媒的不斉脱ブロトン化 / リチウム-水素交換 / キラルアミン / 不斉アルキル化 / ^<15>N-NMR / ^6Li-NMR / X線結晶構造解析 / リチウムブロミド / エナンチオ選択的 |
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| Research Abstract |
Formation and reactions of lithium enolates constitute the most fundamental processes frequently employed in synthetic organic chemistry. We have previously reported novel enantioselective asymmetric deprotonation, alkylation, and protonation reactions. The purpose of the present research is to make these enantioselective asymmetric reactions catalytically asymmetric reactions as to the chiral amines used as chiral auxiliaries.
To make these reactions catalytically asymmetric, it is necessary to find out conditions in which the reactions influenced by chiral auxiliaries proceed reasonably faster than those not influenced by chiral auxiliaries. Based on the studies on the mechanisms of these reactions, we examined various possibilities that satisfy such conditions.
In enantioselective asymmetric deprotonation reactions of prochiral carbonyl compounds. we have found that the rates of deprotonation by bidentate chiral lithium amides proceed faster than those by tridentate lithium amides. We
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have also found that in situ lithium-hydrogen interchange reactions between chiral bidentate amine and achiral tridentate lithium amides occur rapidly favoring the formation of either sides, depending on the structures of these two species. Thus, using a combination of less than a stoichiometric amount of chiral bidentate amines and more than a stoichiometric amount of achiral tridentate lithium amides having appropriate structures, catalytic asymmetric deprotonation reactions as to the chiral bidentate amines were realized for the first time.
In the enantioselective asymmetric alkylation reactions of prochiral lithium enolates, we have found that the rates of alkylation in the presence of bidentate amines are not enhanced, while those in the presence of tetradentate amines are reasonably enhanced. Thus, expecting fast ligand exchange reactions to the lithium between tetradentate chiral amines and bidentate achiral amines, catalytic asymmetric alkylation reactions were realized for the first time using a combination of less than a stoichiometric amount of chiral tetradentate amines and more than a stoichiometric amount of achiral bidentate amines. The same strategy was successfully applied to catalytic asymmetric protonation reactions. Less
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