| Project/Area Number |
05453177
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
HASHIMOTO Shunichi Hokkaido University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (80107391)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Nobuhide Hokkaido University, Faculty of Pharmaceutical Sciences Research Associate, 薬学部, 助手 (80220911)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1994: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1993: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Asymmetric synthesis / Rhodium (II) complex / Carbon-carbon bond forming reactions / Insertion / Diazocarbonyl / Quaternary carbon atom / 2-Indanone / 2-Azetidinone / 位置選択性 / ビシクロ化合物 |
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| Research Abstract |
Dirhodium (II) tetra (triphenylacetate), Rh_2 (O_2CCPh_3) _4, featured by the steric bulk of the bridging ligand on the rhodium exhibits an exceptionally high order of selectivity for CH insertion into methylene over methine in catalytic decompositions of alpha-diazo beta-keto esters appended to a cyclic system. Furthermore, the superiority of this novel catalyst to the commonly used catalysts has also been demonstrated by the virtually complete selectivity for aromatic C-H insertion, thus providing an expedient and general entry to variously substituted 1-alkyl-2-indanones.
A differentiation of enantiotopic methylene C-H bonds can be effected by devising the novel catalyst, dirhodium (II) tetra [N-phthaloyl- (S) -phenylalaninate], of which the phthalimide group has proven to be crucial for this process. It is worthy of note that the enatiomeric excess up to 80% attained here is the highest known to date for enantioselective intramolecular C-H insertion of alpha-diazo beta-keto esters. While the reaction mechanism is presently unclear, the results obtained so far demonstrate that the matched combination of steric effects of the ester moiety and the electron density of the target C-H bond as well as the ligand effects are responsible for high levels of enantioselectivity. By capitalizing on the same catalyst, a highly selective differentiation of enantiotopic benzene rings has been achieved via formal C-H insertion reaction of 3-alkyl-1-diazo-3,3-diphenyl-2-propanones, leading to the formation of (S) -1-alkyl-1-phenyl-2-indanones with up to 95% ee. Dirhodium (II) tetra [N-phthaloyl- (S) -alaninate] has been demonstrated to be useful for the enantioselective construction of heterocyclic systems by decomposition of alpha-carbomethoxy-alpha-diazoacetamides, giving the carbapenem key intermediates of up to 96% ee.
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