炔丙—联烯异构化在成环反应中的研究

发布时间：2018-06-19 18:26

本文选题：炔丙-联烯异构化 + 串联环化反应　；参考：《浙江大学》2017年博士论文

【摘要】：炔丙-联烯异构化因其具有原子经济性和环境友好性的优点,引起了化学工作者的浓厚兴趣,已被广泛地应用于药物分子、天然产物和功能材料的合成中。其中,杂原子促进的炔丙-联烯异构化反应由于可调控范围广,反应活性高而成为有机合成的热点研究领域。本论文主要归纳总结了炔丙-联烯异构化在串联环化反应中的应用,并在此基础上介绍以下内容:1)铑催化的炔丙-联烯异构化合成苯并/噻吩并七元环化合物我们发展了一种砜基导向铑催化的C-H键活化反应,并合成了一系列苯并/噻吩并七元环化合物。该反应过程主要包括砜基导向的铑插入、1,5-氢迁移的炔丙-联烯异构化、分子内的环化和质子交换等过程。氘代实验证实了质子交换的过程,分子内的同位素效应(KIE)表明了 C(sp2)-H键的断裂可能是该反应的决速步。该方法具有操作简便,条件温和的特点,为苯并/噻吩并七元环化合物的合成提供了一条新的途径。2)碱调控的炔丙-联烯异构化合成萘并四元/六元环化合物通过对不同炔丙位质子酸性不同的理解,设计合成了具有炔丙基和炔烯丙基的底物,成功实现了由碱调控的炔丙-联烯异构化/环化过程:当三乙胺作碱时,发生1,5-氢迁移的炔丙-联烯异构化,经历[2+2]环加成及芳构化过程,得到多取代的萘并四元环化合物;当DBU作碱时,发生1,3-H迁移和1,5-H迁移的炔丙-联烯异构化,经历Bergman环化过程,得到多取代的萘并六元环化合物。该反应无需金属催化剂和配体,符合"绿色化学"的要求。3)利用炔丙-联烯异构化策略合成多取代噻吩/萘类化合物我们发展了一种利用炔丙-联烯异构化策略合成多取代萘/噻吩类化合物的方法:当甲硫基与炔丙基处于双键的顺式位置时,发生炔丙-联烯异构化,硫亲核进攻联烯中间碳,得到多取代噻吩类化合物;当甲硫基与炔丙基处于双键的反式位置时,发生炔丙-联烯异构化和6π-电环化反应,得到多取代萘类化合物。该反应底物合成简单,能做成一锅法的串联反应。4)利用现场生成的"CO"对卤代芳烃进行插羰反应和氢化反应的研究我们以TBD为催化剂,以甲酸酯为羰源,实现了 "CO"的现场制备,并将该方法成功地应用到对卤代芳烃的插羰反应中。此外,该反应体系能对邻碘炔丙胺类底物进行环化/氢化反应。底物普适性广,各种取代基的底物都能得到预期产物,产率较高,具有一定的实际应用价值。
[Abstract]:Because of its advantages of atomic economy and environmental friendliness, the isomerization of propargylene-diene has been widely used in the synthesis of drug molecules, natural products and functional materials. The hetero-atom-promoted isomerization of propargyl allylidene has become a hot research field of organic synthesis due to its wide range of control and high activity. In this paper, the application of propargylene-diene isomerization in series cyclization reaction was summarized. On this basis, the following contents are introduced: 1) Rhodium catalyzed isomerization of propargyl allylidene to benzo / thiophene heptagonists We have developed a sulfoxyl rhodium catalyzed C-H bond activation reaction. A series of benzo / thiophene 7-membered ring compounds were synthesized. The reaction process mainly includes sulfoxyl oriented rhodium insertion 1 ~ (1) H ~ (2 +) -transfering propargyl allylene-diene isomerization intramolecular cyclization and proton exchange and so on. The deuterium experiment confirmed the process of proton exchange, and the isotopic effect of KIEs indicated that the fracture of Cnsp _ 2 ~ (-H) bond may be the decisive step of the reaction. The method has the characteristics of simple operation and mild conditions. A new way for the synthesis of benzo / thiophene hepta-ring compounds is provided. 2) Alkali controlled isomerization of propargyl allylidene to naphthalene quaternary / hexagonal ring compounds through different understanding of proton acidity at different proton positions. The substrates with propargyl and propargyl groups were designed and synthesized, and the alkali-regulated isomerization / cyclization process of propargyl allylidene was successfully realized: when triethylamine was used as base, the isomerization of propargyl and diallylidene occurred when triethylamine was used as base. After [22] cycloaddition and aromatization, the polysubstituted naphthalene quaternary compounds were obtained, and when DBU was used as base, the isomerization of propargyl allylidene and allylidene with 1 ~ 3-H migration and 1 ~ (5-H) H migration occurred, and the polysubstituted naphthalene hexadecyclic compounds were obtained through the Bergman cyclization process. The reaction does not require metal catalysts and ligands. (3) Synthesis of polysubstituted thiophene / naphthalene compounds using allylethylene-diene isomerization strategy We have developed a new method for the synthesis of polysubstituted naphthalene / thiophene compounds by isomerization of propargyl propylenes and dienes. Methods: when methylthio and propylidene were in the cis position of double bond, The isomerization of propargylene-diene and the nucleophilic attack of sulfur on the intermediate carbon of diene gave polysubstituted thiophene compounds, and when methylthio and propylidene were in the trans-type position of double bond, the isomerization and 6 蟺 -electrocyclization of propargyl and propargyl took place. Polysubstituted naphthalene compounds were obtained. The synthesis of this reaction substrate is simple and can be made into one-pot series reaction. 4) the in-situ preparation of "CO" has been realized by using "CO" generated in situ for the intercalation and hydrogenation of halogenated aromatics over TBD as catalyst and formate as carbonyl source. The method has been successfully applied to the intercalation carbonylation of halogenated aromatics. In addition, the reaction system can carry out cyclization / hydrogenation of o-iodopropargmine substrates. The substrate is widely used, and all kinds of substrates can get the expected product, and the yield is high, so it has certain practical application value.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25

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