2001 Fiscal Year Final Research Report Summary
Development of Catalytic Enantioselective Reactions Based on the Activation Technology by Chiral Ligands
| Project/Area Number |
10470468
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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 |
TOMIOKA Kiyoshi Graduate School of Pharmaceutical Sciences, Kyoto University, Professor, 薬学研究科(研究院), 教授 (50114575)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Ken-ichi Graduate School of Pharmaceutical Sciences, Kyoto University, Research Associate, 薬学研究科(研究院), 助手 (00335184)
IIDA Akira Graduate School of Pharmaceutical Sciences, Kyoto University, Associate Professor, 薬学研究科(研究院), 助教授 (40202816)
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| Project Period (FY) |
1998 – 2001
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| Keywords | catalytic asymmetric reactions / chiral ligands / conjugate addition / chiral ether ligands / chiral amidophosphine ligands / hemilabile ligands / lithium enolate / lithium thiolate |
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| Research Abstract |
We have developed three types of new activation technology ; the activation of lithium ester enolates by a chiral lithium amide having ether moiety (1), of less reactive organometallic reagents, such as organozinc and organoboran by a complex of a chiral amidophosphine and a transition metal (2), and of lithium thiolate by a chiral amino ether (3).
1. In the presence of a chiral lithium amide having ether moiety, thereaction of lithium ester enolates with imines gave β-lactains in up to 96% yield and 74% ee. This technology was also applicable to the addition of lithium ester enolates to α,β-unsaturated esters to give the adducts in up to 67% yield and 92% ee.
2. In the presence of a catalytic amount of a chiral amidophosphine and copper(II) triflate ; the reaction of 4,4-dimethyl-2-cyclohexenone and diethylzinc gave the ethyl adduct with 64% ee. The application of this amidophosphine-copper-diethylzinc system to the reaction with imine was successful, giving ethyl adducts in up to 97% y
… More
ield and 94% ee. Furthermore, the chiral amidophosphine ligand was applicable to the rhodium-arylboronic acid system. In the presence of a catalytic amount of the chiral amidophosphine and rhodium(I), aryl boronic acidsreacted with 2-alkenones to provide 3-arylalkanones in up to 99% yield and 96% ee. We are accumulating the experimental evidence that the chiral amidophosphine ligand is a so-called hemilabile ligand in this rhodium complex.
3. In the presence of a chiral amino ether, lithium thiolates added to α,β-unsaturated esters and the resulting lithium ester enolate was enantioselectively protonated. Thus, using α,β-unsaturated esters having no β-substitoent, the addncts with up to 92% ee were obtained. When a chiral α,β-unsaturated ester having formyl group was used as an acceptor, the intermediate lithium enolate reacted withthe formyl group in the intramolecular fashion to give cyclized products in good diastereoselectivity. This cyclization was nicely applied to the synthesis of (-)-neplanocin A. Less
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