2006 Fiscal Year Final Research Report Summary
Development of Chiral Organocatalyst and Application to Asymmetric Synthesis
| Project/Area Number |
16390006
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
TAKEMOTO Yoshiji Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (20227060)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIYABE Hideto Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (10289035)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | Thiourea Catalyst / Michael Addition Reaction / Activated Methylene Compounds / Mannich Reaction / β-Amino Acid / Catalytic Asymmetric Reaction / Radical Reaction / Hydrogen-bonding |
|---|
| Research Abstract |
1. We synthesized a new class of bifunctional thiourea catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. The thiourea bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon-center with high enantioselectivity by the Michael reaction.
2. Bifunctional thiourea catalyzed aza-Henry reaction of nitroalkanes to N-Boc-imines, giving syn-β-nitroamines with good to high diastereo- and enantioselectivity. The reaction of N-Boc-imine with various nitroalkanes gave (R)-adducts as major products, whereas the same reaction of N-phosphonoylimines furnished the corresponding (S)-adducts. Synthetic versatility of the addition products was demonstrated by the transformation to chiral piperidine derivatives such as CP-99,994.
3. The PEG-bound thiourea showe
… More
d better catalytic activity than those of the carboxypolystyrene HL resin- and TentaGel carboxy resin-bound ones.
4. Successive treatment of γ,δ-unsaturated β-ketoesters and nitroalkenes with a bifunctional thiourea and TMG promoted the tandem Michael addition, giving rise to highly functionalized cyclohexanones with high diastereo-and enantioselectivity (up to >99% de and 92% ee). The reaction was applied to the asymmetric synthesis of (-)-epibatidine.
5. A thiourea-catalyzed asymmetric Michael addition of activated methylene compounds such as malononitrile, methyl α-cyanoacetate, and nitromethane to α,β-unsaturated imides derived from 2-pyrrolidinone and 2-methoxybenzamide was developed. The Michael adducts were obtained with up to 93% ee.
6. The organocatalytic α-hydrazination of β-keto esters with azodicarboxylates using a bifunctional urea proceeded in high yields and with good enantioselectivity. The scope of the reaction was demonstrated for various substrates and the urea catalyst was revealed to be superior to thiourea.
7. Intermolecular alkyl radical addition to ketimines having 2-phenolic hydroxy group proceeded effectively in aqueous media, providing the novel method for construction of all-substituted sp^3-hybridized carbon center. Less
|
