路易斯酸催化的1,3-偶极环加成反应研究

发布时间：2018-02-03 03:15

本文关键词： 环加成反应不对称催化亚甲胺叶立德环丙烷氮杂环丙烷氰基亚胺　出处：《中国农业大学》2017年博士论文　论文类型：学位论文

【摘要】：1,3-偶极环加成反应是一种合成杂环化合物的重要方法,已广泛应用于天然产物和具有生物活性分子的合成。路易斯酸作用下原位生成的亚甲胺叶立德、路易斯酸催化下环丙烷和氮杂环丙烷开环形成的1,3-偶极子及在碱的作用下原位生成的氰基亚胺作为常用的原位生成的1,3-偶极子都可以参与1,3-偶极环加成反应,基于这些偶极子开发的[3+2]环加成反应已有大量报道,而其他形式的环加成反应则相对较少。在这种背景下,本文旨在发展基于这些偶极子的新型环加成反应,例如[3 + 3]、[6 + 3]、[8+ 3]及双[3 + 2]环加成反应,合成多样性的杂环化合物。基于路易斯酸催化的亚甲胺叶立德与贫电烯及富烯的环加成反应,本文首先发展了铜盐和二茂铁膦氮手性配体形成的催化剂催化的α-亚胺酯与N,N'-环状偶氮次甲基亚胺的不对称[3 + 3]环加成反应,该反应适用于各种芳香取代的底物,可以在温和的反应条件下进行,原料简单易得,可以高收率、高非对映选择性和高对映选择性地得到环加成产物。产物在酸性条件下可以进行差向异构化,在硼氢化锂的作用下可以通过扩环得到含氮和氧的八元环产物。之后我们发展了金属催化的亚甲胺叶立德与环庚三烯酮的[6 + 3]环加成反应,通过银盐和三苯基膦的络合物作为催化剂实现了其消旋催化,通过使用铜盐和二茂铁膦氮手性配体的络合物作为手性催化剂,发展了高对映选择性催化反应。该反应原料易得,条件温和,可以放大量到克级,产物可以在钯碳加氢还原的条件下得到碳碳双键还原的产物,在硼氢化钠的还原条件下得到羰基还原成羟基的产物,证明该反应有很好的实用性。基于路易斯酸可以活化环丙烷和氮杂环丙烷开环形成1,3-偶极子从而进行环加成反应,本文发展了三氟甲磺酸钪催化的1,1-双酯基环丙烷与酞嗪衍生的双氰基叶立德的[3 + 3]环加成反应,该反应可以高收率得到单一的非对映异构体,底物范围广,并可放大量到克级,产物在钯碳还原的条件下能得到一个氰基还原成胺的产物,在硼氢化钠的甲醇溶液中能将产物中一个氰基转换成一个甲氧基。其后本文发展了高氯酸镍催化的氮杂环丙烷与环庚三烯酮的[8 + 3]环加成反应。该反应可放大到克级,产物可以在钯碳还原加氢的条件下进行碳碳双键还原衍生化。本文还发展了氰基亚胺与联烯酯的连续[3 + 2]环加成反应,该反应通过一锅法反应,高收率、高非对映选择性地合成了双吡唑啉螺环化合物,实现了同时构造螺环的两个五元环,并适用于各种取代的氰基亚胺前体和α-取代联烯酯。
[Abstract]:As an important method for the synthesis of heterocyclic compounds, 1H _ 3- dipolar cycloaddition reaction has been widely used in the synthesis of natural products and bioactive molecules. Under the catalysis of Lewis acid, 1 / 3- dipole formed by ring opening of cyclopropane and azacyclopropane and cyanoimide in situ formed under the action of alkaloids can be involved as 1 / 3- dipole, which is commonly used for in situ generation of cyclopropane and azacyclopropane. 3-dipole cycloaddition reactions, based on the. [32] Cycloaddition reactions have been widely reported, while other forms of cycloaddition reactions have been relatively few. In this context, this paper aims to develop new cycloaddition reactions based on these dipoles, such as. [3 3], [6 3], [8 3 / 2. [3 2] cycloaddition reaction to synthesize heterocyclic compounds. Cyclization reaction of methylamine ylide with allene and fulene catalyzed by Lewis acid. In this paper, the catalysts for the chiral ligand formation of copper salt and ferrocene phosphine nitrogen have been developed. The asymmetric properties of 伪 -imide and N- Na-cyclic azomethyl imine catalyzed by copper salt and ferrocene phosphine nitrogen chiral ligands have been developed. [3] cycloaddition reaction, which is suitable for various aromatic substituted substrates, can be carried out under mild reaction conditions, the raw material is simple and easy to obtain, and the yield is high. The cycloaddition products were obtained by high enantioselectivity and high enantioselectivity. Under the action of lithium borohydride, the octa-ring products containing nitrogen and oxygen can be obtained by ring expansion. After that, we have developed metal-catalyzed methylamine ylide and cycloheptylenone. [The complex of silver salt and triphenylphosphine was used as catalyst for racemic catalysis, and the complex of copper salt and ferrocene phosphine nitrogen chiral ligand was used as chiral catalyst. The high enantioselective catalytic reaction was developed. The raw material is easy to be obtained and the conditions are mild. The product can be released to g level and the product can be reduced by carbon and carbon double bond under the condition of palladium carbon hydrogenation. Under the condition of reduction of sodium borohydride, carbonyl group was reduced to hydroxyl group, which proved that this reaction is very practical. Based on Lewis acid, ring opening of cyclopropane and azacyclic propane can be formed. The cycloaddition reaction of 3-dipole was carried out. In this paper, the dicyanoylide derived from 1-diester cyclopropane and phthalazine catalyzed by scandium trifluoromethyl sulfonate was developed. [3] Cycloaddition reaction, this reaction can obtain a single enantiomer in high yield, with a wide range of substrates, and can be put up to the gram level. Under the condition of palladium carbon reduction, a cyanide can be reduced to amine. In methanol solution of sodium borohydride, one cyanide group in the product can be converted into a methoxy group. Subsequently, the catalytic properties of heterocyclic propane and cycloheptylenone catalyzed by nickel perchlorate have been developed. [8 3] cycloaddition reaction. The reaction can be amplified to g order, and the product can be deoxidized by carbon and carbon double bond derivatization under the condition of palladium carbon reduction and hydrogenation. The continuous reaction of cyanoimide and dienyl ester has also been developed. [32] cycloaddition reaction, which synthesized bispyrazoline spirocyclic compounds with high yield and high enantioselectivity by one-pot reaction, and realized the simultaneous construction of two five-member rings of snails. It is suitable for all kinds of substituted cyanoimide precursors and 伪-substituted dienyl esters.
【学位授予单位】：中国农业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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