【作者】 赵爽；

【导师】 唐向阳； 王光伟；

【作者基本信息】 天津大学 ， 化学， 2019， 硕士

【摘要】 四氢喹啉作为关键的化学结构片段广泛存在于药物和天然产物中。在过去几十年,通过[1,5]-氢迁移/环化反应来合成一系列复杂的化合物,尤其是四氢喹啉类衍生物,已经成为一种高效快捷的方法之一。在[1,5]-氢迁移/环化的串联反应中,底物往往需要同时含有氢受体和氢供体两部分。氢供体通常是杂原子邻位惰性的C（sp³）-H键,活化的烯烃、醛、酮、亚胺作为氢受体是比较常见的,但是炔烃作为氢受体却很少有报道。目前,通过[1,5]-氢迁移/环化/氟化反应来合成含有烯基氟片段的四氢喹啉类化合物的方法并未报道,因此开发一种合成不同结构的四氢喹啉类化合物的方法仍然具有很大的发展空间。本论文中,我们设计了一种BF₃·OEt₂参与的炔丙醇重排/[1,5]-氢迁移/环化反应来合成四氢喹啉类化合物的方法。通过对路易斯酸、布朗斯特酸、反应物比例、溶剂、温度等参数的筛选,确定了最佳的反应条件:2.5当量BF₃·OEt₂既可以作为路易斯酸,又可以作为氟源,二氯乙烷（DCE）作为溶剂,在60 ℃条件下反应2小时。反应普适性研究的过程中发现:第一,对于叔胺的类别来说,环状或者脂肪链状的叔胺在标准条件下都可以很好地进行;第二,直接与叁键相连的取代基对反应的结果有很大的影响。当与叁键相连的取代基是芳基或者乙烯基时,可以单一的得到酮式的四氢喹啉类衍生物;而当与叁键相连的取代基是烷基或者三甲基硅基时,主要得到链式的烯基氟类化合物,同时伴随少量酮式的四氢喹啉类衍生物。该方法条件温和高效,可以获得较好收率的四氢喹啉类化合物,还可以根据取代基的不同来合成不同类型的目标产物。因此本论文为合成四氢喹啉类衍生物提供了一种便捷的方法。更多还原

【Abstract】 As one of the most valuable skeletons and building blocks,tetrahydroquinolines can be found in lots of natural products and drugs.In the past few decades,tandem[1,5]-hydride shift（HT）/cyclization reactions proved synthetically powerful for the construction of structurally diverse complicated molecules,especially tetrahydroquinoline derivatives.In the most of[1,5]-HT/cyclization reactions,substrates usually requires to contain both hydride donors and hydride acceptors.The typical hydride donors are C（sp³）–H moiety adjacent to heteroatom.Activated alkenes,aldehydes,ketones,and imines are common as hydrogen acceptors,but alkynes are rarely reported as hydrogen acceptors.Up to now,tetrahydroquinoline compounds containing alkenyl fluoride moiety have never been reported by[1,5]-HT/cyclization/fluorination.Thus,developing a novel approach to synthesize complex tetrahydroquinoline derivatives still has potential application value.In this dissertation,an efficient BF₃·OEt₂-mediated cascade propargyl alcohol rearrangement/[1,5]-HT/cyclization reaction for the synthesis of tetrahydroquinoline derivatives has been described.The optimal reaction conditions were determined by screening of the reaction parameters,such as Lewis acids,Br?nsted acids,solvents,temperature,and the ratio of the reactants.The optimal conditions were chosen as:2.5equivalent of BF₃·OEt₂ can be used as both Lewis acid and fluorine source,1,2-dichloroethane as solvent at 60 ℃ for 2 h.First,for the class of tertiary amines:cyclic or chain tertiary amines can be carried out smoothly under standard conditions;Second,the substituents directly linked to triple bonds have great impact on the results.The ketones can be obtained in a single manner when the aryl or alkenyl are bonded to the triple bond,but alkenyl fluorides can be obtained when alkyl or TMS are attached to the triple bond.This protocol not only can obtain a various of tetrahydroquinoline derivatives with good-to-execllent yields,and different types of target products can be synthesized by changing the substituents.Therefore,this article provides a convenient method to synthesis the tetrahydroquinolines.更多还原