吡唑啉5酮与mbh酯的烯丙基烷基化亲电氟化反应研究-化学专业论文.docxVIP

摘 要 吡唑啉酮作为一类重要的杂环化合物，广泛存在于很多天然产物、医药及农 药分子中。根据氟化学的有关理论，如果将氟原子选择性的引入吡唑啉酮衍生物 的结构单元中，分子的生理活性有可能得到显著提高。因此，探索有效构建氟代 吡唑啉酮衍生物的方法具有十分重要的理论意义和潜在的应用价值。 MBH 酯（Morita-Baylis-Hillman carbonates）作为一种多官能团化合物，在 有机合成中得到了广泛应用。近年来人们对 MBH 酯的官能团转化反应做了大量 工作，尤其是有机小分子催化的的烯丙基烷基化反应得到了系统的研究。本文研 究了在 1,4-二氮双环[2.2.2]辛烷（DABCO）作用下，吡唑啉-5-酮与 MBH 酯、 NFSI 的“一锅”烯丙基烷基化/亲电氟化反应，以 40?83%的收率、最高 85:15 的非对映选择性合成了 18 个 4-氟代-4-烯丙基取代的吡唑啉-5-酮衍生物；进一步 将该串联反应扩展到 NCS 及 NBS，同样得到相应的氯代及溴代吡唑啉-5-酮类化 合物。与此同时，我们通过改变反应条件，成功实现了对不同类型氟代吡唑啉-5- 酮衍生物的合成。 关键词：吡唑啉-5-酮，MBH 酯，烯丙基烷基化反应，亲电氟化 Abstract Pyrazolone derivatives, an important class of aza-heterocycles, are very useful compounds serving as building blocks for the synthesis of natural products, medicines, and agrochemicals. Based on the theory of fluorine chemistry, the introduction of fluorine atom into pyrazolone molecules may significantly impact the physicochemical properties of these compounds. However, the use and preparation of fluorinated pyrazolones is extremely rare. Therefore, development of rapid and efficient methods for the synthesis of fluorinated pyrazolones is still in great demand. As multifunctional compounds, MBH carbonates have been widely used in organic synthesis. Functional group transformation of MBH carbonates has been extensively studied in the past decades, especially for its organocatalytic asymmetric allylic alkylation reactions with a wide range of nucleophiles. In this thesis, we developed a DABCO-mediated one-pot sequential transformation of pyrazolones with Morita-Baylis-Hillman (MBH) carbonates and N-fluoro-N-(phenylsulfonyl) benzenesulfonamide (NFSI) via allylic alkylation/ electrophilic fluorination. By using this process, a series of fluorinated pyrazolin-5-ones were synthesized in moderate to high yields (40–83%) with up to 85:15 dr under mild conditions. Further extension of this one-pot sequential reaction to other halogenating reagents, such as NBS and NCS, also proved effective. Additionally, other fluorinated pyrazolin-5-one deriva