Fluorination based on addition of molecular fluorine to conjugated enones

在分子的特定位置引入氟原子，无论是从化学角度还是从药学角度来看，都是非常重要的任务。虽然分子氟是最经济的亲电氟化试剂，但它通常被认为活性太强，不能进行定点氟化。我们研究了基于分子氟加成共轭烯酮的有机分子的高效氟化。我们发现4-甲氧基-或4-氯-2-吡喃在低温下被分子氟选择性地氟化在3-位或5-位。我们还发现，α-羟亚甲基羰基化合物的氟化反应高产率地得到了a-氟羰基化合物。通过这种氟化方法，还合成了3-氟-2-喹诺酮类化合物。3-氟-2-喹诺酮类化合物是乙酰基苯胺氟化制得的α-氟基乙酰基苯胺类化合物与分子氟的环合反应。双乙烯酮与分子氟反应，生成的氟化物与苯胺反应生成γ-氟乙酰基苯胺类化合物，再经环合得到4-氟甲基-2-喹诺酮类化合物。

Introduction of fluorine atoms in specific site of molecules is very important task from both chemical and pharmaceutical points of view. Though molecular fluorine is the most economical as the electrophilic fluorinating reagent, it is normally regarded as being too reactive for site-specific fluorination. We studied efficient fluorination of organic molecules based on addition of molecular fluorine to conjugated enones. We found that 4-methoxy- or 4-chloro- 2-pyrones are selectively fluorinated at the 3- or 5-position by molecular fluorine at a low temperature. We also found that fluorination of α-hydroxymethylene carbonyl compounds affords a-fluoro carbonyl compounds in high yields. By this fluorination method, 3-fluoro-2-quinolones are also synthesized. 3-Fluoro-2-quinolones are alternatively synthesized cyclization of α-fluoroacetoasetanilides obtained by fluorination of acetoasetanilides with molecular fluorine. Reaction of diketene with molecular fluorine followed by treatment of the resulting fluoride with anilines produced γ-fluoroacetoasetanilides, which on cyclization afforded 4-fluoromethyl- 2-quinolones.