1996 Fiscal Year Final Research Report Summary
Development of Electrophilic and Enantioselective Fluorinating Agents based on Fine Chemisty Design
| Project/Area Number |
07807193
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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 | Grant-in-Aid for Scientific Research (C) (2) |
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Principal Investigator |
TAKEUCHI Yoshio Toyama. Med. Pharm Univ. Fac. Pharm. Sci. Professor, 薬学部, 教授 (20111750)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Enantioselective Fluorination / Electrophilic Fluorination / Benzothiazolidine / alpha-phenethylamine / N-fluorosulfonamide / fluorine gas / perchloryl fluoride / X-ray analysis |
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| Research Abstract |
1) (S)-Valine and (S)-phenylglycine were converted into 4-substituted 2-oxazolidinone and 2-thiazolidinone, respectively. Attempted fluorination of these compounds gave N-fluoro derivative only for the former compound.
2) Saccarin was treated with two kinds of alkyl metal reagents to produce 3, 3-disubstituted 2, 3-dihydrobenzo [1, 2-d] isothiazole 1, 1-dioxides. These compounds were treated with 10-(+) - champhorsulfonyl chloride to give diastereomers, which were separated. Each diastereomer was hydrolyzed to give (R)- or (S) -N-H derivative. Fluorination of the (R) -3-methyl-3-cyclohexyl derivative (1) with fluorine gas produced the corresponding (R) -N-F compound (2) successfully.
3) Attempted fluorination of N-tosyl, N-mesyl, and N-triflyl derivatives of (S) -alpha-phenethylamine yielded the corresponding N-F derivatives only for the two former compounds. However, the stereoselectivity of the C-fluorination employing these N-F derivatives was low.
4) C-Fluorination of 2-methyl-1-tetralone (3), 2-benzyl-1-tetralone, and ethyl 2-oxo-cyclopentanecarboxylate was attempted employing the new N-F reagent 2. Bast result was obtained when 3 was treated with LDA/THF/50ﾟC - 0ﾟC and then allowed to react with 2 to afford the C-fluorinated product in 81% yield with ee of 80%.
5) Compound 1, champhorsulfonyl derivative of 1, compound 2 were dubjected to X-ray crystallographic analyzes. Based on the stereochemistry around the nitrogen atoms of these compounds, stereoselectivity of the fluorination reaction was investigated form mechanistic viewpoint.
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