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题名: 亚胺酸酯参与/Brook重排介导的多组分反应研究
作者: 韩晓军
答辩日期: 2014-05-30
导师: 卢崇道
专业: 有机化学
授予单位: 中国科学院大学
授予地点: 北京
学位: 博士
关键词: 多组分反应 ; 亚胺酸酯 ; α-硅基胺 ; Brook重排 ; 格氏试剂
摘要: 从相对简单易得的原料出发,用“一锅煮”的方法高效地形成多个化学键,中间不经分离,直接得到复杂结构的分子,这一直是合成化学家不断追求的目标之一。而多组分反应由于具有连续、高效,操作简便,反应收率高等优点,越来越受到化学家的青睐。近些年来用亲电试剂捕捉硅基Brook重排产生的碳负离子的多组分反应,由于其在合成多羟基/氨基/羧基天然产物方面的独特优势,这激发了人们对相关领域的研究兴趣。α-芳基取代的α-羰基酯/靛红衍生物作为易得的α-羰基类化合物,其α-羰基被硅基亲核加成后发生Brook重排产生碳负离子,其结构中的芳基和酯/酰胺基都对碳负离子有稳定效用,因此产生的碳负离子可能被亲电试剂捕捉,发生连续反应,本论文对此方面进行了研究。亚胺酸酯由于其特殊结构(含有氮、氧两个杂原子和类酯、亚胺结构),在一些复杂结构的构建上可能会有特殊优势,但是相关研究报道很少,因此本论文对其参与合成α-季碳-α-硅基胺的多组分反应进行了研究。本论文研究的主要内容和取得的结果如下:
1、开创了一个高效灵活地合成α-季碳-α-硅基胺的新方法,即在一个反应瓶内通过对亚胺酸酯、硅锂试剂和格氏试剂的三组分反应“一锅煮”合成此类大位阻的目标产物。该方法灵活高效,产率可高达95%,底物适用性和反应耐受性都很好,解决了大位阻的α-季碳-α-硅基胺类化合物难于合成的问题。同时也初次合成出了系列芳香亚胺酸酯,为芳香亚胺酸酯方面研究提供了方法参考。亚胺酸酯和硅锂试剂的两组分反应通过控制反应的淬灭条件,能够以较高的产率得到三类不同的化合物——硅基N,O-缩酮、酰硅和硅基亚胺,这是合成这三类化合物行之有效的方法。
2、研究了硅锂试剂、α-羰基酯/靛红类化合物和亲电试剂亚胺/醛参与的三组分反应,该类反应能够一步构建含有多个官能团(氨基、羟基、羧基等)的β-氨基/羟基-α-季碳羟基酯/酰胺类化合物骨架,其中包括一个季碳中心。反应底物适用性很好,产率中等到较高(最高可达99%),非对映选择性较低(d.r.值在5:1到1:1之间)。
3、以手性的芳香N-叔丁基亚磺酰亚胺酸酯为原料,通过仲碳烷基格氏试剂(R2CH-MgX)对其加成还原,高产率(最高可达98%)、较高非对映选择性(d.r. >20:1 to 8:1)地合成出手性胺类化合物。该方法与亚胺和格氏试剂反应的合成法比较,优点是前者不会产生亚胺被还原的副产物(芳香亚胺和异丙基格氏试剂反应,主要得到亚胺被还原的产物,而非异丙基加成产物)。该反应的发现有效拓展了亚胺酸酯在合成转化上的应用。
英文摘要: Abstract Xiao-Jun Han(Organic Chemistry) Directed by Prof. Chong-Dao Lu It has been a constant pursuit of synthetic chemists to obtain complex molecules from commercial or easily prepared reagents in a one-pot operation without isolation of intermediates. Multicomponent reactions (MCRs) have attracted considerable attention due to the virtue of their convergence, productivity, operationally simple and generally high yields of products. In recent years, the multicomponent reactions involving stabilized carbanions that formed from Brook rearrangement and can be trapped by electrophiles have shown unique advantages in the synthesis of compounds that contain hydroxyl/amino/carboxyl groups, which stimulated the reasearch interests of synthetic community. α-Aryl-α-carbonyl ester/isatin derivatives, as the readily available carbonyl compounds, can be attacked by nuclephilic silyl groups and followed by silyl migration ([1,2]-Brook rearrangement), resulting in carbanions that can be stabilized by the aryl groups and carboxyl groups of the intermediates. Subsueqently, the carbanion can be trapped by electrophiles and completed this [1,2]-Brook rearrangement-mediated tandem reaction. Studies on this aspect have been conducted in this thesis. Imidates, because of their special structure (containing two hetero atoms - nitrogen and oxygen, similar ester and imine structure), may have special reactivities and display some advantages in the construction of some structurally complex molecules. But few studies about imidates were reported. So we studied the multicomponent reactions involving cascade transformation of imidates for the synthesis of α-tertiary α-silylamine. In the dissertation, we mainly focused on the subjects listed as below: 1. An efficient method for the synthesis of α-tertiaryα-silylamines has been developed. The three-component coupling of aryl tosylimidates, silyllithium, and Grignard reagents in a single flask enables the rapid construction of diverse bulky α-silylamine derivatives. The synthetic method is flexible and efficient with yield up to 95% and the reaction was well tolerated. Meanwhile, we have succeeded in synthesis of a series of aryl tosylimidates, which provide effective procedures for their preparation. In the reaction of imidates and silyllithium, three kinds of products including silyl N,O-aminal, acylsilane and acylsilane-derived imine can be obtained respectively by using different reaction quenching conditions. This is also an effective method for the synthesis of these compounds. 2. Three-component reactions of silyllithium, α-carbonyl ester/isatin compound and an electrophilic imine/aldehyde have been studied. The reaction occurred smoothly to furnish densely functionalized β-amino/hydroxy-α-hydroxy esters with a quaternary carbon center in one-pot operation. This reaction can be extended to broad substrates in moderate to high yield (up to 99%), albeit with low to moderate diastereoselectivity (d.r. from 5:1 to 1:1). 3. A high yielding (up to 98%) and excellent diastereoselective (d.r. >20:1 to 8:1) method for the synthesis of α-chiral amines via the addition-reduction reaction of chiral N- N-tert-butylsulfinyl arylimidates and secondary Grignard reagents R2CH-MgX. This synthetic protocol did not suffer from the side reaction that the reaction of secondary Grignard reagents and imines always encountered. In the latter protocol, competing hydride transfer is sometimes dominated reaction pathway over the desired nuclephilic addition of secondary alkyl groups to imines. The disclosure of the described reactivity of N-tert-butylsulfinyl arylimidates has extended their applications in the organic transformations.
内容类型: 学位论文
URI标识: http://ir.xjipc.cas.cn/handle/365002/3427
Appears in Collections:资源化学研究室_学位论文

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作者单位: 中国科学院新疆理化技术研究所

Recommended Citation:
韩晓军. 亚胺酸酯参与/Brook重排介导的多组分反应研究[D]. 北京. 中国科学院大学. 2014.
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