XJIPC OpenIR  > 资源化学研究室
Thesis Advisor卢崇道
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline有机化学
KeywordAza-brook重排 连续反应 多组分反应 苯炔 环加成 Β-氨基酮 氮杂环丙烷

连续反应和多组分反应以其高效构建化学键和分子多样性的特点而备受推崇,其中Brook重排(硅基C→O迁移)介导的该类反应便是一种被广泛研究而行之有效的手段。相反,由于aza-Brook重排能垒较高、反应的驱动力不足等特点,导致aza-Brook重排成功的例子并不多见。自然界中广泛存在含有胺基官能化的化合物,而aza-Brook重排在该类结构的合成中具有潜在的应用价值,因此开展与该硅基迁移相关的化学转化研究具有重要意义。本论文首先研究了碱作用下的aza-Brook重排引致的连续反应,发现了首例硅基[1,4]-Csp2→N迁移,分子内的硅基重排引发了芳炔中间体的生成,该中间体与[1,3]-偶极体、1,4-双烯体发生环加成反应,得到环加成产物。对于呋喃类底物,分子间和分子内的反应均获得了近乎定量的收率。研究中发现碱的选择对引发aza-Brook重排尤为重要,并且硅基迁移指向位点N上的取代基对硅基重排有着显著的影响,同时影响环加成的区域选择性和立体选择性。这一[1,4]-aza-Brook重排引致的芳炔环加成反应与传统的氟离子介导的芳炔环加成反应相比,有着效率高、产率高、副产物少的特点。其次,研究了[1,3]-aza-Brook重排介导的腈、硅基二氯甲烷和(RS)-叔丁基亚磺酰亚胺的三组分反应,一锅合成β-氨基酮和C-氯代氮杂环丙烷。研究发现硅基的选择和添加剂HMPA(六甲基磷酰三胺)对反应的化学选择性和立体选择性具有决定性影响,建立了三种最优反应条件分别合成了(RS, R)-β-氨基酮、(RS, S, S)-和(RS, R, R)-C-氯代氮杂环丙烷。此三组分反应具有高效、高立体选择性、底物适用性广的特点,显示了aza-Brook重排作为构建含氮化合物的应用价值。最后比较研究了Brook重排与aza-Brook重排,发现了aza-Brook重排存在[1,2]-硅基消除、对温度敏感、对金属离子敏感等Brook重排所具有的诸多特点。研究发现胺基上连接手性叔丁基亚磺酰基的反应底物良好地保持了aza-Brook重排活性,这使发展aza-Brook重排介导的不对称反应成为可能。

Other Abstract

Cascade and muti-component reactions have attracted increasing attention of synthetic community due to their high efficiency in the construction of chemical bonds and molecular diversity. Among these reactions, the transformations involving Brook rearrangement, which is silyl migration from carbon to oxygen, had been extensively investigated and proved to be effective methods for the synthesis of oxygen-containing compounds. On the contrary, the successful examples of aza-Brook rearrangement are rare, since the high activation energy barrier and usually insufficient driving force. However, the nitrogen containing compounds widely exist in nature and the transformations involving aza-Brook rearrangement have great potential in the synthesis of these compounds. For the reasons mentioned above, the development of this C→N silyl migration chemistry is of significant importance. At first, we explored the cascade reaction triggered by aza-Brook rearrangement for the synthesis of amino-functionalized aromatic compounds. The first successful example of [1,4]-aza-Brook rearrangement was disclosed that enables in situ benzyne formation and subsequent efficiently cycloaddition with [1,3]-dipoles and dienes. When furan derivatives were used as substrates, these reaction give nearly quantative yield in both intermolecular and intramolecular cycloadditions. We found that usage of a suitable base was important to the success of the aza-Brook rearrangement. Also, the nature of the substituent on the amino group affects the silyl migration and subsequent cycloaddition in both regioselctivity and stereoselctivity. Compared with the conventional fluorine ion-triggered benzyne cycloadditions,this [1,4]-aza-Brook rearrangement miediated protocol is more efficient giving higher yield and less byproducts. Next, we investigated the [1,3]-aza-Brook rearrangement mediated three-component reaction of nitriles, silyldichloromethanes, and (R)-tert-utanesulfinylimines. Our investigations indicated that silyl group and HMPA (hexamethylphosphoric triamide) have a decisive influence on chemoselectivity and stereoselctivity. Optimal reaction conditions for the synthesis of (RS, R)-β-aminoketones, (RS, S, S)- and (RS, S, S)-C-chloroaziridines have been developed. Notable features of this three-component reaction include high efficiency, high stereoselectivity, and wide substrates tolerance. The described reaction serve as a successful example of the application of aza-Brook rearrangement in synthesis of nitrogen containing compounds. Finally, a comparative study of Brook and aza-Brook rearrangement was conducted and as a result we found that the phenomenon observed in the transformation of the later such as [1,2]-silyl elimination as well as effect of the temperature and metal counterion is also observed in the cases of the former. We also noticed that the chiral tert-butanesulfinyl group on amino group is compatible with aza-Brook rearrangement, which indicated that the development of an asymmertric version of aza-Brook rearrangement mediated reaction might be possible.

Document Type学位论文
Recommended Citation
GB/T 7714
黄泽傲. Aza-Brook重排引致的连续反应和多组分反应研究[D]. 北京. 中国科学院大学,2015.
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