1999 Fiscal Year Final Research Report Summary
Studies on the Development of Novel Asymmetric Multi-Functional MPV Reduction
| Project/Area Number |
09470489
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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 Pharmaceutical University |
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Principal Investigator |
NODE Manabu Kyoto Pharmaceutical University, Professor, 薬学部, 教授 (60027076)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDE Kiyoharu Kyoto Pharmaceutical University, Associate Professor, 薬学部, 助教授 (10237711)
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| Project Period (FY) |
1997 – 1999
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| Keywords | α,β-Unsaturated Compounds / Chinal Mercapto Alcohols / Asymmetric Tandem Michael-MPV Reaction / Anymmetric 1,7-Hydride Shift / Dynamic Kinetic Resolution / Asymmetric Protonation / Asymmetric Bifunctional Group Exchange Reaction / Optically Active Alcohols |
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| Research Abstract |
The introduction of a thiol group into a chiral alcohol regent for asymmetric Meerwein-Ponndorf-Verley (MPV) reductions allows asymmetric reduction of α,β-unsaturated ketones to secondary alcohols and allylic alcohols via a novel tandem Michael addition/MPV reduction. The reaction of acyclic α,β-unsaturated ketones and (-)-10-mecaptoisoborneol using dimethylaluminum chloride afforded the MPV reduction products diastereoselectively in very high yields (up to 96%). Mechanistic studies elucidated : (1) the structure of the chelation complex with (-)-isoborneol and dimenthylalumium chloride, (2) an asymmetric 1,7-hydride shift, and 3) dynamic kinetic resolution via reversible Michael addition. Subsequent reductive desulfurization of the MPV products with a modified Raney nickel system led to the highly enantioselective reduction of α,β-unsaturated ketones to saturated secondary alcohols in 96-98% ee. β-Elimination of the corresponding sulfoxides gave the allylic alcohols in 86-98% ee. Appl
… More
ications to the asymmetric reduction of a synthetic intermediate of prostaglandins and to a new asymmetric synthesis of the (+)-Rove beetle pheromone was developed.
Optically active 1,3-mercapto alcohol were synthesized from α,β-unsaturated ketones using (-)-2-mercaptomethylisoborneol in two steps. The transformation involved the above tandem reaction and a base catalyzed elimination. The two newly created carbons in tras-chalcone derivatives were enantioselectively controlled to a high degree. Using the above transformation, an asymmetric bifunctional group exchange reaction between the substrate and chiral reagent was developed.
A highly asymmetric protonation of Michael addition of thiol to α-substituted α,β-unsaturated esters using a chiral mercapto alcohol was found. Subsequent cleavage of the chiral auxiliary from the product would formally furnish an asymmetric Michael addition of hydrogen sulfide to α-substitute α,β-unsaturated esters. In the tandem reaction of α-substituted α,β-unsaturated ketones, configurations of the newly generated three sequential carbons were also highly controlled. However, attempts to remove the chiral auxiliary from the product are unsuccessful to far. Less
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