2003 Fiscal Year Final Research Report Summary
Development of carbon-carbon bond forming reaction under environmentally benign conditions and its application to combinatorial synthesis
| Project/Area Number |
13557197
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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 | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
NAITO Takeaki Kobe Pharmaceutical University, Professor, 薬学部, 教授 (00068339)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Okiko Kobe Pharmaceutical University, Associate Professor, 薬学部, 助教授 (90102110)
UEDA Masafumi Kobe Pharmaceutical University, Assistant Professor, 薬学部, 助手 (00340935)
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| Project Period (FY) |
2001 – 2003
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| Keywords | environmentally benign / radical reaction / carbon-carbon bond formation / one-pot / solid-phase reaction / aqueous solvent / Fischer indolization / rearrangement |
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| Research Abstract |
1. Carbon-carbon bond formation by radical reaction
The use of water as a solvent has generated considerable interest from both economical and environmental points of view. Employment of a moisture-resistant radical species would eliminate the cumbersome operations involved in conventional ionic reactions. We have developed novel carbon-carbon forming reactions employing radical as a crucial reaction species and aqueous media as solvent. Newly-found radical reactions are proved to be synthetically useful by completing synthesis of several biologically active compounds.
Triethylborane, zinc metal, and indium are selected as a radical initiator. The first ionization potential of indium is as low as that of lithium and sodium but indium is stable in water. Triethylborane-, zinc-, and indium-mediated carbon-carbon bond forming reactions proceeded smoothly even in aqueous media to afford alkyl radical addition products. We also investigated diastereoselective radical addition reaction of chir
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al substrates carrying the Oppolzer's camphorsultam and found that these stereoselective radical reactions are very efficient and highly promising approach to biologically active compounds such as α-amino acids and heterocycles. The radical reactions using three initiators were successfully extended to intramolecular radical addition cyclization reactions. Particularly, indium-mediated intramolecular reaction with alkyl iodide in water provides efficient tandem addition-cyclization-trap reaction.
The solid-phase tandem radical reactions of oxime ethers proceeded effectively under iodine atom-transfer reaction conditions to give the azacydes or chiral oxacycles after cleavage of the resin.
2. Rearrangement reaction under mild conditions
Rearrangement reaction is one of atom-economy reactions. We investigated 1,2-Wittig rearrangement of hydroximates under the basic conditions and found that chiral hydroximate containing phenethyl alcohol moiety on nitrogen of the oxime ether group undertook effective rearrangement to afford hydroxy oxime ether which was successfully converted into (+)-cytoxazone. Based upon our previous work on [3,3]-sigmatropic rearrangement of hydrazones under the acylating conditions, we succeeded in the synthesis of natural indole compounds. Additionally, novel and efficient synthetic method for benzofurans is developed via the route involving sigmatropic rearrangement followed by cyclization under the mild reaction conditions. Less
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Research Products
(46 results)
