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N-叔丁基亚磺酰基亚胺酯/脒α位的不对称官能化研究
马鹏举
Subtype博士
Thesis Advisor卢崇道
2018-05-30
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline有机化学
KeywordN-叔丁基亚磺酰基亚胺酯/脒 非对映选择性 羟胺化 羟基化 酰硅
Abstract

作为手性氨合成子,手性叔丁基亚磺酰胺是一种廉价易得、性能优良的手性助剂,同时也是许多手性有机硫配体和催化剂的前体。叔丁基亚磺酰胺与醛、酮缩合得到的手性亚胺作为亲电试剂可以与各种不同结构的亲核试剂发生立体选择性反应,非对映选择性得到结构多样的手性胺类化合物。然而,关于手性叔丁基亚磺酰亚胺/亚胺酯/脒等α位烯醇化,所形成的氮杂烯醇负离子官能化反应的研究报道却相对较少也比较局限。N-叔丁基亚磺酰基氮杂烯醇负离子对亲电试剂加成所形成的亚胺/亚胺酯/脒等又可继续充当手性亲电试剂参与后续反应,所以在合成中有着重要的应用前景。基于此,本文对N-叔丁基亚磺酰基氮杂烯醇负离子的官能化反应进行了以下拓展性研究工作。 首先,我们研究了N-叔丁基亚磺酰基亚胺酯α位的不对称羟胺化反应。NaHMDS作用下,N-叔丁基亚磺酰基亚胺酯烯醇化得到的氮杂烯醇负离子中间体可以被芳香亚硝基化合物捕捉生成α-羟胺基亚胺酯类化合物,且反应普遍具有较高的非对映选择性和良好的收率。另外,当亚胺酯基α位为芳基取代时,反应在催化量碱的存在下即可进行。我们在锌/醋酸的条件下切断了羟胺化产物的N?O键,然后以有机金属试剂对其加成得到了具有实用合成价值的手性α-芳胺基取代亚胺和1,2-二胺。 其次,我们研究了N-叔丁基亚磺酰基亚胺酯和脒α位的不对称羟基化反应。N-叔丁基亚磺酰基亚胺酯或脒以NaHMDS为碱,烯醇化得到氮杂烯醇负离子,然后与氧气发生反应生成α-过氧化物中间体,随即被体系中的亚磷酸三甲酯原位还原并质子化得到α-羟基亚胺酯或脒。反应的普适性研究显示,对于各类α位脂肪基和芳基取代的亚胺酯或脒,反应都具有很好的反应收率(高达99%)和非对映选择性(>20:1 dr)。另外,我们还对α-羟基化产物进行了结构衍生,得到了一系列手性α-羟基羧酸衍生物和1,2-氨基醇。 最后,我们对N-叔丁基亚磺酰基亚胺酯和酰硅的反应进行了初步研究。以NaHMDS为碱,四氢呋喃为反应溶剂,N-叔丁基亚磺酰基亚胺酯烯醇化得到的氮杂烯醇负离子对酰硅发生亲核加成,然后经1,2-Brook重排生成α-硅氧基苄基碳负离子,随后该中间体发生分子内的Mannich反应,立体选择性地生成多取代环丙烷产物;以t-BuOK为碱,甲苯为溶剂,氮杂烯醇负离子对酰硅发生亲核加成产生的α-硅氧基碳负离子中间体并没有发生关环反应,而是立体专一性质子化生成了α位具有取代基的β-硅氧基亚胺酯。

Other Abstract

tert-Butanesulfinamide is a inexpensive and readily available chiral ammonia synthon as well as versatile precursor of some chiral organosulfur ligands and catalysts. As chiral electrophiles, N-tert-butanesulfinylimines, formed from condensation of aldehydes or ketones with tert-butanesulfinamide, have been heavily used in the nucleophilic addition reactions to access diverse chiral amines with high levels of diastereocontrol. By contrast, functionalization of N-tert-butanesulfinyl aza-enolates that derived from corresponding imines, imidates or amidines has received less attention. Addition of N-tert-butanesulfinyl aza-enolate to electrophiles generates α-functionalized imines, imidates or amidines that are suitable precursors for further electrophilic transformations.This thesis focuses on the diastereoselective α-functionalization of N-tert-butanesulfinyl imidates or amidines. In the first part, asymmetric α-hydroxyamination of N-tert-butanesulfinyl imidates was investigated. With sodium bis(trimethylsilyl)amide as base, the enolized N-tert-butanesulfinyl imidates can be diastereoselectively captured by nitrosoarenes to afford α-hydroxyamino imidates in good yields with general excellent diastereoselectivities. Notably, the hydroxyamination of α-aryl substituted N-tert-butanesulfinyl imidates can be realized by using a catalytic amount of base. After N?O bond cleavage of α-hydroxyamino imidates using Zn/AcOH, additions of organometallic reagents to the α-arylamino imidate products gave α-amino imines and 1,2-diamines. Furthermore, asymmetric α-hydroxylation of imidates and amidines was developed. The aza-enolates generated from deprotonation of α-alkyl substituted N-tert-butanesulfinyl imidates or α-aryl substituted N-tert-butanesulfinyl amidines by sodium bis(trimethylsilyl) amide can be intercepted by oxygen with excellent diastereocontrol and subsequently transformed into α-hydroxylation products in the presence of the reductant trimethyl phosphite. A range of α-alkyl imidates and α-aryl amidinesunderwent smooth reaction with oxygen providing α-hydroxylated products in high yields with high diastereoselectivities. Manipulations of the imidate/amidine group on the α-hydroxylated products afforded the the corresponding carboxylic acid derivatives and 1,2-amino alcohol. Finally, we have examined the reaction of N-tert-butanesulfinyl imidates with acylsilanes. In the presence of sodium bis(tromethylsilyl) amide in THF, nucleophilic addition of aza-enolates that derived from N-tert-butanesulfinyl imidates to aroylsilanes was followed by 1,2-Brook rearrangement, which generates α-silyloxy benzyl carbanions, and subsequent intramolecular Mannich reaction gave poly-substituted cyclopropanes. Using potassium tert-butoxide as base in toluene, the α-silyloxy carbanion intermediates underwent stereospecific protonation, rather than intramolecular cyclization, to afford α-substituted-β-silyloxy imidates.

Pages188
Document Type学位论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/5445
Collection资源化学研究室
Recommended Citation
GB/T 7714
马鹏举. N-叔丁基亚磺酰基亚胺酯/脒α位的不对称官能化研究[D]. 北京. 中国科学院大学,2018.
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