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。2）以Saccarin为原料，用两种烷基金属试剂反应，合成了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-（+）-樟脑磺酰氯处理，得到非对映异构体，将其分离。将每种非对映异构体水解，得到（R）-或（S）-N-H衍生物。（R）-3-甲基-3-环己基衍生物（1）用氟气氟化，成功地得到了相应的（R）-N-F化合物（2）。（3）（S）-α-苯乙胺的N-甲苯磺酰基、N-甲磺酰基和N-三氟甲磺酰基衍生物的氟化，只得到了前两种化合物相应的N-F衍生物。然而，使用这些N-F衍生物的C-C1的立体选择性较低。4）尝试使用新的N-F试剂2对2-甲基-1-四氢萘酮（3）、2-苄基-1-四氢萘酮和2-氧代-环戊烷羧酸乙酯进行C-氟化。5）对化合物1、1的磺酰基衍生物、化合物2进行了X-射线单晶衍射分析。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缩合反应的立体选择性。

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.