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
KeywordBrook 重排 多组分反应 N-磺酰γ-内脒 N-叔丁基亚磺酰亚胺 手性二
Other Abstract

酰硅化合物是[1,2]-Brook 重排反应的重要起始物,其与亲核试剂反应发生重排之后形成的碳负离子中间体可以被分子内或分子间的亲电试剂捕捉,形成Brook 排介导的连续反应。对酰硅类化合物的亲核加成引发的[1,2]-Brook 重排介导的连续反应中,以烷基卤代物,羰基化合物和1,4-加成受体作为捕捉试剂的反应方法学研究较多,而以亚胺作为捕捉试剂的研究报道相对较少(手性亚胺作为亲电试剂的研究则未见报道)。手性叔丁基亚磺酰亚胺作为亚胺亲电反应的经典的立体化学控制工具,将其借鉴并引入Brook 重排介导的连续反应中,立体选择性地构建某些特殊结构的手性化合物或天然产物骨架,对于拓展Brook 重排反应的应用范围具有重要意义。

本论文首先研究了N-芳基磺酰亚胺酸酯,酰硅酯和手性叔丁基亚磺酰醛亚胺的三组分连续反应,以中等到较好的收率一步构建多取代的手性(3R, 4R)-N-磺酰γ-脒。反应表现出优异的化学选择性、立体选择性(d.r. > 20100)和光学选择性(9499%ee)。反应的立体化学通过6/4 元环过渡态得到很好的控制,一锅反应操作形成两个CC 键(连续的手性中心),一个OSi 键,一个CN 键,同时脱去手性助剂(手性叔丁基亚磺酰基团)。在上述研究的基础上,本论文研究了有机锂试剂/格氏试剂,酰硅酯和手性叔丁基亚磺酰醛/酮亚胺的三组分串联反应。该反应可以高立体选择性地一步构筑手性β-氨基-α-季碳羟基酯结构。实验结果表明不同的金属试剂引发的反应可以得到不同构型的β-氨基-α-季碳羟基酯化合物。对于有机锂试剂,甲基锂参与的反应表现出良好的非对映选择性(d.r. > 20100);而对于格氏试剂,甲基格氏试剂参与的反应的非对映选择性稍差(d.r. > 10100),并且所得产物的立体构型与甲基锂的反应不同。最后本论文初步研究了亚胺的还原偶联反应。Ti(OiPr)4/2iPrMgCl 还原芳基醛亚胺形成钛-亚胺复合物,与叔丁基亚磺酰醛亚胺反应,通过叔丁基亚磺酰基团作为手性助剂控制亚胺加成的立体选择性,合成手性二胺。


As a useful conjunctive reagents, acylsilanes have played an important role in initiating [1,2]-Brook rearrangement-mediated tandem reactions. The tandem bond formation strategies involve nucleophilic addition to the acylsilane to generate, after [1,2]-Brook rearrangement, a stabilized carbanion intermediate which can be trapped by the second electrophile intermolecularly or intramolecularly. Although, alkyl halides, carbonyl compounds and Michael acceptors are widely utilized in the [1,2]-Brook rearrangement-mediated tandem reactions, there is only one report based on the trapping of the carbonion intermediate with imines. To the best of our knowledge, there is no report employing chiral imines as the second electrophile in the [1,2]-Brook rearrangement-mediated tandem reactions. Over the past decade, N-tert-butanesulfinyl imines have played a significant role in the stereochemical control of electrophilic addition reations. Therefore, it is of great significance to carry on research on Brook rearrangement-mediated multi-component reactions for the highly diastereoselecctive synthesis of chiral compounds with special structure or the key skeleton of natural products, using the N-tert-butanesulfinyl imines as the electrophile .We have developed a novel three-component coupling reaction of N-sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines in one-pot. The cascade reaction affords an efficient synthesis of polysubstituted optical (3R, 4R)-N- sulfonyl γ-amidines in moderate to good yields. This reaction occurs with exquisite chemoselectivity, excellent diastereoselectivity (d.r. > 20∶1∶0∶0), and excellent enantioselectivity (94–99% ee). The observed stereochemistry for the additions can be rationalized by Ellman’s six/four-membered bicyclic transition state. The cascade promotes the formation of two C–C bonds (contiguous stereogenic carbons), one C–N bond, and one O–Si bond, together with cleavage of the chiral auxiliary (tert-butanesulfinyl group) in a one-pot operation.Based on the aforementioned research results, we then achieved a highly diastereoselective three-component reaction of organometallic reagents, silyl glyoxylates and N-tert-butanesulfinyl imines. This reaction occurred smoothly to furnish densely functionalized β-amino-α-hydroxyesters with quaternary stereocenters in one-pot. Preliminary results indicate that the organometallic reagents are critical to the configurations of the desired products of β-amino-α-hydroxyesters. For the organolithium reagents, the reaction can provide the desired products with high diastereoselectivity (d.r. > 20∶1∶0∶0) when the methyl lithium was used as the first nucleophile. For the Grignard reagents, reaction employing methyl Grignard reagent as the first component affords β-amino-α-hydroxyesters with good diastereoselectivity (d.r. > 10∶1∶0∶0), and the absolute configuration of the product is different with the methyl lithium initiated reaction.Finally, we have developed a reductive coupling reaction of imines. In situ generated titanium-imine complexes from imines and Ti(OiPr)4/2iPrMgCl react with N-tert-butanesulfinyl aldimines to afford chiral vicinal diamines. tert-Butanesulfinyl group was used as chiral auxiliary to control the stereoselectivity of the coupling reaction of imines.

Document Type学位论文
Recommended Citation
GB/T 7714
姚明. Brook重排介导的多组分反应研究[D]. 北京. 中国科学院大学,2013.
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