Development of Electrophilic and Enantioselective Fluorinating Agents based on Fine Chemisty Design

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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.