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

1) (S)-缬氨酸和(S)-苯甘氨酸分别转化为4-取代的2-恶唑烷酮和2-噻唑烷酮。对这两种化合物进行氟化处理后，只得到前一种化合物的n -氟衍生物。2)用两种烷基金属试剂对糖精进行处理，制得3,3 -二取代2,3 -二氢苯并[1,2 -d]异噻唑1,1 -二氧化物。这些化合物用10-(+)-香磺酰氯处理得到非对映体并分离。每个非对映体水解得到(R)-或(S) - n - h衍生物。(R) -3-甲基-3-环己基衍生物(1)与氟气成功氟化生成相应的(R) -N-F化合物(2)。3)对(S) - -苯乙胺的n -甲酰基、n -甲酰基和n -三氟酰基衍生物进行氟化反应，只得到前两种化合物对应的N-F衍生物。然而，使用这些N-F衍生物的c -氟化反应的立体选择性很低。4)采用新的N-F试剂，尝试了2-甲基-1-四酮(3)、2-苄基-1-四酮和2-氧-环戊烷羧酸乙酯的c -氟化反应。以LDA/THF/50 / C- 0 C处理3，然后与2反应得到收率81%，ee为80%的氟化产物。5)对化合物1、1的香樟磺酰衍生物、化合物2进行x射线晶体学分析。基于这些化合物氮原子周围的立体化学，从机理的角度研究了氟化反应的立体选择性。

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.