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2-恶唑烷酮和2-噻唑烷酮。2)用两种烷基金属试剂与3，3-二取代2，3-二氢苯并[1，2-d]异噻唑1，1-氧化物反应，得到3，3-二取代的2，3-二氢苯并[1，2-d]异噻唑1，1-氧化物。这些化合物用10-(+)-香酚磺酰氯处理得到非对映异构体，并将其分离。每个非对映异构体均经水解得到(R)-或(S)-N-H衍生物。(R)-3-甲基-3-环己基衍生物(1)在氟气中氟化得到相应的(R)-N-F化合物(2)。3)(S)-α-苯乙胺的N-对甲苯磺基、N-甲苯基和N-三氟基衍生物的氟化尝试仅对前两种化合物产生相应的N-F衍生物。4)用新的N-F试剂2对2-甲基-1-四酮(3)、2-苄基-1-四酮和2-氧代环戊烷羧酸乙酯进行了C-氟化反应，得到了最好的结果。当3用LDA/THF/50ﾟC-0ﾟC处理后，再与2反应生成C-氟化产物，产率为81%，ee为80%。5)化合物1，1，2的香酚磺基衍生物进行了X射线晶体分析。基于这些化合物的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.