萘氧氨基醇催β-酮酸酯不对称α-羟基化研究
发布时间：2018-07-18 15:10
【摘要】：手性α-羟基-β-二羰基化合物广泛存在于天然产物、药物、农用化学品、功能化学品中,是一类重要功能化合物的结构单元。制备该类化合物的不对称催化方法主要通过金属有机不对称催化和有机小分子不对称催化。金属有机不对称催化对β-二羰基化合物的α-羟基化反应研究的较成熟且系统,然而不对称有机催化的研究报道较少,需要发现高效、安全、廉价的催化体系。 手性β-氨基醇类化合物作为催化剂广泛应用于催化Aldole反应、Michael加成反应、烯烃环氧化等反应。在本课题组研究苯氧氨基醇催化剂的基础上,本文研究了萘氧氨基醇作为有机催化剂催化β-酮酸酯的不对称羟基化反应。以商业易得的2,7-二萘酚为原料合成了8个萘氧氨基醇催化剂(A1-A8),其中A2-A7均为未见文献报道的新化合物,并使用红外、核磁、质谱对上述8个化合物进行了结构表征。其中对A8-c进行了XRD单晶衍射分析,对其空间结构进行了确认。 对A1～A8萘氧氨基醇催化剂催化β-酮酸酯不对称羟基化的筛选,发现催化剂A5催化5-氯-茚酮羧酸甲酯(1a)具有较高对映选择性,是最优催化剂。通过对反应溶剂、温度、反应时间、底物浓度等反应条件的优化,催化剂A5催化5-氯-茚酮羧酸甲酯羟基化获得了63%ee及99%的产率。同时对催化其它14个β-酮酸酯底物进行了研究,考察了催化剂的底物适用性。最后对A5催化1a不对称羟基化的机理进行了推测。
[Abstract]:Chiral 伪 -hydroxy- 尾 -dicarbonyl compounds are widely found in natural products, drugs, agricultural chemicals and functional chemicals, which are the structural units of a class of important functional compounds. The asymmetric catalytic methods for the preparation of these compounds are mainly metal-organic asymmetric catalysis and organic small molecule asymmetric catalysis. The studies on 伪 -hydroxylation of 尾 -dicarbonyl compounds by metallometallic asymmetric catalysis are more mature and systematic. However, there are few reports on asymmetric organic catalysis, which requires the discovery of efficient, safe and inexpensive catalytic systems. Chiral 尾 -aminoalcohols are widely used as catalysts for Aldole reaction and epoxidation of olefins. Based on the study of phenoxyamino alcohol catalyst, the asymmetric hydroxylation of 尾 -ketoacid ester catalyzed by naphthoxy amino alcohol as organic catalyst was studied in this paper. Eight naphthyloxyamino alcohol catalysts (A1-A8) were synthesized from commercially readily available 2-dinaphthol. Among them, A2-A7 were all new compounds not reported in the literature. The structures of the eight compounds were characterized by IR, NMR and MS. The spatial structure of A8-c was confirmed by XRD single crystal diffraction analysis. The asymmetric hydroxylation of 尾 -keto ester catalyzed by A1~A8 naphthoxy amino alcohol catalyst was screened. It was found that catalyst A5 was the best catalyst for the enantioselectivity of methyl 5-chloro-indenone carboxylate (1a). By optimizing the reaction conditions such as solvent, temperature, reaction time and substrate concentration, the catalyst A5 was used to catalyze the hydroxylation of methyl 5-chloro-indenone carboxylic acid with the yield of 63% and 99%. At the same time, the other 14 substrates of 尾 -ketoacid ester were studied, and the applicability of the substrates was investigated. Finally, the mechanism of asymmetric hydroxylation of 1a catalyzed by A5 was speculated.
【学位授予单位】：大连理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943
本文编号：2132292
[Abstract]:Chiral 伪 -hydroxy- 尾 -dicarbonyl compounds are widely found in natural products, drugs, agricultural chemicals and functional chemicals, which are the structural units of a class of important functional compounds. The asymmetric catalytic methods for the preparation of these compounds are mainly metal-organic asymmetric catalysis and organic small molecule asymmetric catalysis. The studies on 伪 -hydroxylation of 尾 -dicarbonyl compounds by metallometallic asymmetric catalysis are more mature and systematic. However, there are few reports on asymmetric organic catalysis, which requires the discovery of efficient, safe and inexpensive catalytic systems. Chiral 尾 -aminoalcohols are widely used as catalysts for Aldole reaction and epoxidation of olefins. Based on the study of phenoxyamino alcohol catalyst, the asymmetric hydroxylation of 尾 -ketoacid ester catalyzed by naphthoxy amino alcohol as organic catalyst was studied in this paper. Eight naphthyloxyamino alcohol catalysts (A1-A8) were synthesized from commercially readily available 2-dinaphthol. Among them, A2-A7 were all new compounds not reported in the literature. The structures of the eight compounds were characterized by IR, NMR and MS. The spatial structure of A8-c was confirmed by XRD single crystal diffraction analysis. The asymmetric hydroxylation of 尾 -keto ester catalyzed by A1~A8 naphthoxy amino alcohol catalyst was screened. It was found that catalyst A5 was the best catalyst for the enantioselectivity of methyl 5-chloro-indenone carboxylate (1a). By optimizing the reaction conditions such as solvent, temperature, reaction time and substrate concentration, the catalyst A5 was used to catalyze the hydroxylation of methyl 5-chloro-indenone carboxylic acid with the yield of 63% and 99%. At the same time, the other 14 substrates of 尾 -ketoacid ester were studied, and the applicability of the substrates was investigated. Finally, the mechanism of asymmetric hydroxylation of 1a catalyzed by A5 was speculated.
【学位授予单位】：大连理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943
【参考文献】
相关期刊论文 前1条
1 时憧宇;杜玲枝;;手性二茂铁基β-氨基醇的合成及其在催化硼氢化钠/碘对潜手性酮的不对称还原反应中的应用[J];河南大学学报(自然科学版);2008年05期
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