【作者】 张辉；

【导师】 曲红梅； 吴巍；

【作者基本信息】 天津大学 ， 制药工程， 2018， 硕士

【摘要】 茂锆试剂在金属有机化学中具有重大用途,它们可以发生环加成、偶联等各种反应,对于新药物、新材料的发现有着重要的意义。尽管已经有大量关于由茂锆试剂诱导合成多取代苯的研究,但是对于由茂锆试剂诱导,合成含有苯环结构硅内酯,以及多取代苯在茂锆试剂诱导下的衍生化,从而获得更多新型的分子骨架的研究报道较少。本文在课题组对锆化学的研究基础之上,首先提出了一种通过茂锆试剂诱导,以炔烃为底物,在二丁基二茂锆根岸试剂的作用下,与丁炔二酸二酯进行[2+2+2]环加成反应,进而在碘化试剂的作用下,得到几种新型的含有苯环结构硅内酯的新方法。其中1,1-二甲基-4-羧酸乙酯基-6,7-二苯基-5-(三甲基硅烷基)-1,3-二氢苯并[c][1,2]氧硅杂环戊二烯-3(1H)酮(硅内酯a)的收率为43%,1,1-二甲基-4-羧酸乙酯基-6,7-二苯基-5-碘-1,3-二氢苯并[c][1,2]氧硅杂环戊二烯-3(1H)酮(硅内酯b)的收率为36%。本文也对由茂锆试剂诱导生成的锆杂环戊二烯进行了卤代芳烃偶联的研究,得到了共轭二烯的结构,并进行了单晶培养和晶体研究分析。其次,本文对由茂锆试剂诱导生成的含有酯基结构的多取代苯进行酯基衍生化研究,对多取代苯的酯基采用氢化铝锂还原,得到了苄醇的结构,苄醇在不同氧化试剂(PDC、PCC、DDQ、Swern、Dess-Martin等)的氧化作用下,成功得到了几种未曾报导过的新型分子骨架结构,5,6-二丙基-1-(3H)-异苯并呋喃酮,收率47%~54%;4,5,6,7-四丙基-1-(3H)-异苯并呋喃酮,收率81%~85%;4,5,6,7-四丙基-1,3-二氢异苯并呋喃-1-醇,收率63%,并通过核磁分析,确定了它们的结构。本文还对由茂锆试剂诱导生成的多取代苯进行了扩环衍生化研究,对于多取代苯的酯基采用氢化铝锂还原,得到了苄醇结构,苄醇卤代后,与炔烃发生偶联,进而在二丁基二茂锆的作用下,与丁炔二酸二酯发生环加成反应,扩环后的二氢蒽类衍生物的酯基在氢化铝锂的作用下,还原为苄醇,进而在PDC氧化剂的氧化作用下,得到了两种未曾报道过的新型分子骨架结构。5,10-二氢蒽[2,3-C]呋喃-1-(3H)-酮,收率68%;4,6,7,8,9,11-六丙基-5,10-二氢蒽[2,3-C]呋喃-1-(3H)-酮,收率为61%。本文不仅能拓宽茂锆试剂方法学和锆杂环戊二烯的用途,还发展了合成几种新型骨架分子的方法,同时为后续这些分子的应用前景研究奠定基础。更多还原

【Abstract】 Zirconocene reagents have great applications in metal organic chemistry.They can undergo a variety of reactions such as cycloaddition and coupling,and are of great significance for the discovery of new drugs and new materials.Although there has been a great deal of research on the synthesis of poly-substituted benzenes by zirconocene reagents,there are few reports on the formation of silalactones with benzene structure and the derivatization of poly-substituted benzene under the induction by zirconocene reagents.In this way,many new molecular skeletons can be obtained.Based on the research of zirconium chemistry in our previous research,a new method to synthesize several new sillactones with benzene structure is discovered.Mediated by zirconocene reagent,the alkyne substrate reacts with the Negishi reagent ZrCp₂Bu₂ to afford the Zirconacyclopentadienes,which participates the[2+2+2]cycloaddition reaction with alkynes and followed by derivation reaction under the action of iodinated reagents.The yield of sillactone a is 43%,the yield of sillactone b is 36%,and the structures are confirmed by ¹H NMR and ¹³C NMR.In the meantime,the coupling of halogenated aromatics and zirconacyclopentadienes mediated by zirconocene reagent is also studied,and the structure of conjugated dienes is obtained.For the obtained benzene ring-containing sillactone and conjugated diene,single crystal analysis is performed.Secondly,ester-based derivatization of poly-substituted benzenes with ester groups induced by zirconocene reagents is also studied.The ester groups of poly-substituted benzene is reduced with lithium aluminum hydride to obtain the structure of benzyl alcohol.Under the action of oxidants,such as oxidant（PDC,PCC,DDQ,Swern,Dess-Martin and so on）,several novel molecular frameworks that have not been reported yet are discovered.The yield of 5,6-dipropyl-1-（3H）-isobenzofuran-one is 47%-54%,the yield of 4,5,6,7-tetrapropyl-1-（3H）–isobenzofuran is 81%-85%,the yield of 4,5,6,7-tetrapropyl-1,3-dihydroisobenzofuran-1-ol is 63%,and their structures are confirmed by NMR.In this paper,the ring-expanded derivatization of poly-substituted benzene induced by the zirconocene reagent is also studied.The benzyl alcohol structure is obtained by the reduction of the ester groups in the presence of lithium aluminum hydride.After the benzyl alcohol is halogenated,the halogenated benzyl alcohol reacts with the butynedioic acid diester under the action of dibutyl zirconocene.The ester groups of the expanded dihydroanthracene derivative undergoes reduction in the presence of lithium aluminum hydride,and then under the oxidative effect of PDC oxidant,two kinds of novel molecular framework structures that have not been reported are discovered.Dihydroanthracene[2,3-C]furan-1-（3H）-one was obtained in a yield of68%;4,6,7,8,9,11-hexamethyl-5,10-Anthracene[2,3-C]furan-1-（3H）-one in 61%yield.This article can not only broaden the use of zirconocene reagents and zirconylcyclopentadiene,but also provide a method for the synthesis of several new framework molecules,and lay the foundation for the future application of these molecules.更多还原