2004 Fiscal Year Final Research Report Summary
Development of a New Generation of Nucleophilic Catalysts and their Use in Selective Reactions
| Project/Area Number |
14370721
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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 | Kyoto University |
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Principal Investigator |
KAWABATA Takeo Kyoto University, Institute for Chemical Research, Professor, 化学研究所, 教授 (50214680)
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| Co-Investigator(Kenkyū-buntansha) |
TSUBAKI Kazunori Kyoto University, Institute for Chemical Research, Associate Professor, 化学研究所, 助教授 (50303897)
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| Project Period (FY) |
2002 – 2004
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| Keywords | nucleophilic catalysts / acylation / kinetic resolution / regioselectivity / desymmetrization / remote asymmetric induction / acceleration |
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| Research Abstract |
Organocatalysis has been the focus of curent synthetic attention due to environmental benignity and the mild reaction conditions. We have developed a chiral 4-pyrrolidinopyridine (PPY) analogue which has no chiral elements near the catalytically active pyridine nitrogen. Nevertheless, this catalyst shows high enantioselectivity (s=10〜54) in the kinetic resolution of racemic amino alcohols with a p-dimethylaminobenzoyl protective group. In this research project, the mechanism for the enantioselective acylation and enantioselective acceleration was clarified. The rate of acylation of an amino alcohol derivative with the catalyst was found 12 times as fast as that with PPY. C_2-symmetric chiral PPY analogues were also developed. A key intermediate, 2,5-dicarboxyl-N-pyridyl-pyrrolidine, was obtained via a five-step sequence starting from L-glutamic acid. Combinatorial introduction of the functional side chains at C(2) and C(5) is readily achieved, thus, construction of a small library of chiral C_2-symmetric PPYs was accomplished. All of these new PPY analogues showed high catalytic activity for acylation of alcohols, because of no steric congestion near the catalytically active pyridine nitrogen. They showed excellent selectivity in acylative asymmetric desymmetrization of cyclic meso-diols at room temperature.
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