基于钯催化串联反应合成苯并杂环化合物的研究

发布时间：2018-06-23 01:21

本文选题：杂环化合物 + Heck偶联　；参考：《浙江工业大学》2017年硕士论文

【摘要】：杂环化合物普遍存在于天然产物和药物分子的结构单元之中,因此发展简洁、高效、方便的方法来构建杂环化合物具有重要的意义。串联反应作为一类具备这些优点的原子经济性反应,是一种合成杂环化合物的有力策略,受到了人们的重视。论文研究基于膦催化缺电子联烯极性反转加成产物(Z)-2-[苯氧基(芳基)]次甲基-2-丁烯酸酯的基础上,以钯作催化剂,通过分子间Heck偶联/分子内烯丙基化串联反应合成苯并杂环化合物。选择以N-(2-碘苯基)-4-甲基苯磺酰胺类化合物和(Z)-2-[苯氧基(芳基)]次甲基-2-丁烯酸酯类化合物为原料,在钯催化下发生Heck偶联/烯丙基化串联反应合成27个新型吲哚啉衍生物,收率达28%-81%。通过对该反应的温度、溶剂、碱和催化剂等条件进行优化,确定最佳反应条件为Pd(dppe)Cl2作催化剂,NaHCO3作碱,n-Bu4NCl作添加剂,DMF为溶剂,130 oC下反应12小时。(Z)-2-[苯氧基(芳基)]次甲基-2-丁烯酸酯类化合物通过发生掘氢消除反应形成共轭二烯中间体,再与N-(2-碘苯基)-4-甲基苯磺酰胺类化合物在钯催化下发生分子间Heck偶联和分子内烯丙基化反应得到27个目标产物,并利用1H NMR、13C NMR、IR和HRMS等分析手段对目标化合物进行了结构表征。选择以邻碘苄醇和(Z)-2-[苯氧基(芳基)]次甲基-2-丁烯酸酯为原料,在钯催化下发生Heck偶联/烯丙基化串联反应合成异色满衍生物。(Z)-2-[苯氧基(芳基)]次甲基-2-丁烯酸酯通过发生掘氢消除反应形成共轭二烯中间体,再与邻碘苄醇在钯催化下发生分子间Heck偶联和分子内烯丙基化反应得到目标产物。通过对该反应的温度、溶剂、碱和催化剂等条件进行优化,利用1H NMR、13C NMR和IR等分析手段对目标化合物进行了结构表征,但目标产物(E)-2-(异苯并二氢吡喃-3-基)-3-苯基丙烯酸乙酯的产率仍小于25%,这部分工作还需继续研究。
[Abstract]:Heterocyclic compounds are commonly found in the structural units of natural products and drug molecules, so it is of great significance to develop simple, efficient and convenient methods to construct heterocyclic compounds. As a kind of atomic economy reaction with these advantages, tandem reaction is a kind of powerful strategy for the synthesis of heterocyclic compounds. Based on phosphine catalyzed polar inversion addition product (Z) -2- [phenoxy (aryl)] methyl-2-butenate, palladium was used as catalyst. Benzo heterocyclic compounds were synthesized by intermolecular Heck coupling / intramolecular allylation tandem reaction. Twenty-seven novel indoline derivatives were synthesized from N- (2-iodophenyl) -4-methylphenylsulfonamide compounds and (Z) -2- [phenoxy (aryl)] methylene -2-butenate esters under the catalysis of palladium catalyzed by Heck coupling / allylation series reaction. The yield is 28- 81. By optimizing the reaction temperature, solvent, alkali and catalyst, The optimum reaction conditions were determined as follows: (Z) -2- [phenoxy (aryl)] methylene -2-butenic acid ester compounds formed conjugated diene intermediates by hydrogen extraction reaction when PD (dppe) Cl _ 2 was used as catalyst and NaHCO _ 3 as base n-Bu4NCl _ 2 as additive and as solvent 130oC for 12 hours, (Z) -2- [phenoxy (aryl)] methylethyl -2-butenic acid esters. Furthermore, 27 target products were obtained by palladium catalyzed Heck coupling and intramolecular allylation with N- (2-iodophenyl) -4-methylbenzenesulfonamide. The structures of the target compounds were characterized by 1H-NMR-13C NMR-IR and HRMS. Using o-iodobenzyl alcohol and (Z) -2- [phenoxy (aryl)] methylene -2-butenate as raw materials, Under the catalysis of palladium, a series reaction of Heck coupling / allylation was carried out to synthesize the isocolor derivatives. (Z) -2- [phenoxy (aryl)] methylene -2-butenate was synthesized into conjugated diene intermediates by hydrogen removal reaction. The target product was obtained by Heck coupling and intramolecular allylation with o-iodobenzyl alcohol catalyzed by palladium. The reaction temperature, solvent, alkali and catalyst were optimized, and the target compounds were characterized by 1H-NMR-13C NMR and IR. However, the yield of the target product (E) -2- (isobenzodihydropyran -3-yl) -3-phenylacrylate is still less than 25%.
【学位授予单位】：浙江工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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