单线态氧促进的α-酮酸脱羧与胺的酰胺化反应

发布时间：2018-04-13 11:35

本文选题：脱羧酰胺化 + 单线态氧　；参考：《合肥工业大学》2017年硕士论文

【摘要】：酰胺是普遍存在的有机官能团,作为蛋白质基本构建骨架的酰胺键,不但在生命中扮演着重要角色,也大量存在于药物活性分子和材料中。因此,对于酰胺的合成研究一直受到极大关注。众所周知,羧酸或者羧酸衍生物与胺的缩合反应是合成酰胺最普遍的策略,但由于这些方法有很多不足之处,比如需要对其他官能团进行保护,活化的羧酸衍生物稳定性差,以及较低的化学选择性,因此寻找稳定的酰基合成子试剂就成为了研究热点。最近,α-酮酸已经用作新的酰基供体。已有许多工作报道了通过α-酮酸成功构建了C-C键反应,而构建C-N键的研究极少。在此背景下,我们发展了一种温和条件下无催化剂的α-酮酸脱羧与胺的酰胺化反应。该反应避免了金属残留,而且底物范围广泛,包括吸电子或者含卤素的苯胺也能很好兼容。此外,该反应还能进行放大。同时,也展示了羧基与酮酸基对胺以及酮酸对氨基和羟基的良好化学选择性。初步机理实验研究表明,α-酮酸与胺先脱水缩合产生亚胺羧酸中间体,接着由在光照条件下产生的单线态氧进行氧化脱羧,产生亚胺自由基,随后经过水解过程生成烯醇式化合物,经互变异构产生目标产物酰胺。~(18)-氧同位素标记实验表明,产物酰胺的羰基氧极有可能来源于溶剂水中的氧原子。我们提出的单线态氧促进的氧化脱羧体系正在适用其他脱羧交叉偶联反应。
[Abstract]:Amide is a common organic functional group. As a basic skeleton of protein, amide bond plays an important role in life, but also exists in a large number of drug active molecules and materials.Therefore, the synthesis of amides has attracted much attention.It is well known that condensation of carboxylic acids or derivatives of carboxylic acids with amines is the most common strategy for the synthesis of amides, but these methods have many shortcomings, such as the need to protect other functional groups and the poor stability of activated carboxylic acid derivatives.And low chemical selectivity, so the search for stable acyl synthesizer has become a research hotspot.Recently, 伪-ketoic acid has been used as a new acyl donor.It has been reported that the C-C bond was successfully constructed by 伪 -ketoacid, but the construction of C-N bond was seldom studied.In this context, we developed an amidation reaction of 伪 -ketoacid decarboxylation with amines without catalyst under mild conditions.The reaction avoids metal residues and is compatible with a wide range of substrates, including electron absorption or halogen-containing aniline.In addition, the reaction can be amplified.At the same time, the good chemical selectivity of carboxyl group and ketoacid p-amine and ketoacid p-amino group and hydroxyl group were also demonstrated.The experimental results show that the intermediate of imine carboxylic acid is produced by dehydration and condensation of 伪 -ketoic acid and amine, and then oxidized decarboxylation is carried out by the singlet oxygen produced under illumination to produce imine free radical.After hydrolysis, enol compounds were formed, and the target product, amides, was produced by tautomerism. The results showed that the carbonyl oxygen of the product was probably derived from the oxygen atoms in the solvent water, and the oxygen isotope labeling experiment showed that the carbonyl oxygen of the product was probably derived from the oxygen atom in the solvent water.Our proposed oxidative decarboxylation system promoted by singlet oxygen is being applied to other decarboxylation cross-coupling reactions.
【学位授予单位】：合肥工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.25

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