1996 Fiscal Year Final Research Report Summary
Synthetic Study on Chiral ortho-Lithiation Reaction and Their Application for Natural Products
| Project/Area Number |
07672272
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nagasaki University |
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Principal Investigator |
WATANABE Mitsuaki Nagasaki University, Center for Instrumental Analysis, Associate Professor, 計測・分析センター, 助教授 (10039654)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Yoshihiro Nagasaki University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60026309)
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| Project Period (FY) |
1995 – 1996
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| Keywords | ortho-Lithiation Reaction / Asymmetric Synthesis / Oxidative Homocoupling / Sparteine / 1,2-Diphenyl-1,2-ethanediol / 1,2-Diphenylsuccinic Acid |
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| Research Abstract |
The investigators succeeded in development of following useful method for chiral lithiation reaction of aromatic ring systems such as tertiary benzamides, o-formylbenzamides, O-substituted benzylalcohols, and phenylacetic acid derivatives.
1. The lithiation of tertiary benzamide such as N,N-diethylbenzamide with (-) -sparteine-s-BuLi complex base followed by addition of aliphatic aldehydes gave 3-alkylphthalides after lactonization under basic conditions. However, the yields of 3-alkylphthalides obtained here were quite low and then the above reaction could not accept as general and asymmetric synthesis for aromatic compounds.
2. The reaction of N,N-diethyl o-formylbenzamide with (-) -sparteine-n-BuLi complex base gave (R) -3-butylphthalide, essential oil of celery, with 3.5%ee in good yield after lactonization of the amido-alcohol intermediate.
3. The reaction of chiral amide, derived from o-phthalaldehydic acid chloride and (S) -2-methoxymethylpyrrolidine, with n-BuLi gave (S) -3-butylp
… More
hthalide with 5.3%ee in good yield.
4. The lithiation of benzylalcohol derivatives such as methylether, methoxymethylether, and carbamates were investigated under various conditions. The lithiation of N,N-diisopropyl O-carbamate of benzylalcohol using (-) -sparteine-s-BuLi complex followed by addition of benzaldehyde gave (S,S) -1,2-diphenyl-1,2-ethanediol with 10.5%ee in moderate yield after deprotection using LAH.
5. The homocoupling of O-carbamates of benzylalcohol under the conditions ; (-) -sparteine-s-BuLi and then 1,2-dibromoethane as oxidizing agent, gave (S,S) -1,2-diphenyl-1,2-ethanediol with 20%ee in 75% yield.
6. A simple and convenient procedure for the stereoselective homocoupling of various phenylacetic acid esters were investigated. The methods using EGB (electrochemically generated base) derived from pyrrolidone to generate an anion of phenylacetic acid ester and subsequent use of iodine as an oxidizing agent or simple use of titanium tetrachloride-triethylamine gave predominantly dl-2,3-diphenylsuccinic acid ester in good yields. Less
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