【作者】 张明；

【导师】 朱成建； 胡宏纹；

【作者基本信息】 南京大学 ， 有机化学（专业学位）， 2011， 博士

【摘要】 本论文中,我们报道了首例氢转移条件下金催化芳香醛的还原氨基化反应,研究了金配合物在无溶剂条件下催化合成β-烯胺酮(酯)类化合物。同时我们还拓展了β-烯胺酮(酯)类化合物在合成吲哚喹啉酮和多取代吡咯衍生物中的应用。本论文的研究工作主要包括：第一部分：氢转移条件下金催化芳香醛的还原氨基化反应氢转移反应是有机化学中最重要和最有应用合成价值的反应之一。非均相的金催化氢转移反应已经有文献报道,但均相的金催化氢转移反应还没有被研究。我们采用了—价金催化剂,常见的汉斯酯为氢源,在温和的反应条件下高效地实现了醛与胺生成仲胺的反应过程。研究过程中发现不同类型芳香族的胺可以与芳香族的醛、含有杂原子的芳醛发生氢转移反应。链状丁酮和环状酯肪类酮(环戊酮、环己酮)在加热条件下也可以发生同样的反应。反应可能经历了质子催化的过程：催化剂(PPh3)AuOTf由于吸收空气中的水汽部分水解,生成的氢正离子与反应过程中形成的亚胺结合成亚胺正离子,它然后被汉斯酯还原为仲胺。我们首次实现了金催化的均相氢转移反应,为均相金催化的其他氢转移反应提供了借鉴。第二部分：无溶剂条件下金催化合成的β-烯胺酮(酯)化合物伊烯胺酮(酯)化合物是一类非常有用的合成中间体。文献报道三价的金也可以催化这类型的反应,但对于反应过程中,胺的种类很少,芳香族参与此反应时候,产率较低。为改善这样的研究结果,我们发展了一类以一价金配合物为催化剂,在室温无溶剂的条件下,较高产率的实现了β-烯胺酮(酯)衍生物的合成。脂肪胺与芳香胺都可以很好的参与反应生成对应的β-烯胺酮与β-烯胺酯类化合物。这个反应具有简易的操作,温和的反应条件及较高的产率。第三部分：金催化吲哚醌类化合物合成在第二章节我们发展了一种高效实用的β-烯胺酮(酯)化合物合成方法,为拓展其应用,我们以2-溴萘1,4-二酮为原料合成具有生物活性的杂原子化合物。我们筛选了不同的反应条件,摸索不同的试剂,对它们的优劣进行了比较。研究过程中发现烯胺酯与烯胺酮底物中,当胺的取代基团为脂肪类取代基时候,反应效果非常的好；当胺的取代基团为芳香类取代基团时候,反应效果很差。我们开拓了金配合物在合成这类型具有生物活性分子的新方向,为金催化合成其他具有生物活性物质提供了借鉴。第四部分：金催化多取代吡咯的合成多取代吡咯是一类非常重要化合物,在生理和医药上面具有很重要的应用前景。常规合成多取代吡咯的方法是Knorr反应,Paal-Knorr反应和Hantzsch反应,但是他们反应条件比较苛刻,较低的产率以及很长的反应时间。因此发展简单、高效、条件温和的合成方法是非常必要的。我们采用了硝基苯乙烯与不同的β-烯胺酮(酯)进行反应,高效的得到了多取代的吡咯衍生物。催化剂的用量仅仅为1m01%。更多还原

【Abstract】 In this thesis, we have discovered that gold(Ⅰ) complex catalyzed reductive amination of aromatic aldehydes under transfer hydrogenation conditions. We also developed an efficient synthetic method for β-enaminones and β-enaminoesters catalyzed by gold(Ⅰ) under solvent-free conditions. We extended the application of β-enaminones and β-enaminoesters in synthesis of indolequione and polysubstituted pyrrole derivatives.The research work of this thesis includes:Part1. Direct reductive amination of aromatic aldehydes catalyzed by gold(Ⅰ) complex under transfer hydrogenation conditionsTransfer hydrogenation reaction is one of the most significant and synthetically useful methods in organic chemistry. In the past decades, there were few reports shown that supported gold nanoclusters are efficient heterogeneous catalysts for transfer hydrogenation. However, there was no one report the homogeneous gold catalyzed transfer hydrogen reaction. The direct reductive amination of aromatic aldehydes has been achieved with excellent isolated yields using readily accessible Ph3PAuCl/AgOTf catalyst along with ethyl Hantzsch ester as hydrogen source under mild reaction conditions. Aromatic amines could reacted with aromatic aldehydes and heteroaromatic aldehydes smoothly. When aliphatic ketones were used, such as butanone, cyclopentanone and cyclohexanone, good yields were obtained at higher reaction temperature. The catalytic mechanism for this reaction is probably through a proton-catalyzed hydride transfer process. The catalyst Ph3PAuOTf is partially hydrolyzed with traces of water, and provides the proton which can protonate the imine. The resulting iminium can then be reduced by the ethyl Hantzsch ester as the hydride source.Part2. Efficient synthetic method fo β-enaminones and β-enaminoesters catalyzed by gold(Ⅰ) under solvent-free conditions.β-Enaminones and β-enaminoesters are highly useful building blocks that play crucial roles in the synthesis of heterocycles and biologically active compounds. Arcadi reported gold (Ⅲ) derivatives could catalyze the condensation reaction of1,3-dicarbonyls and ammonia/amines, however, the kinds of amines were limited and low yiled was obtained when aromatic amines was used. An efficient method has been developed for synthesis of β-enaminones and β-enaminoesters via reaction of1,3-dicarbonyl compounds with various aliphatic and aromatic primary amines catalyzed by [(PPh3)AuCl]/AgOTf under solvent-free conditions. This methodology affords kinds of β-enaminones and β-enaminoesters derivatives in good to excellent yields. Moreover, the method has the advantage of easy manipulation and mild reaction conditions.Part3. Synthesis of indolequiones through bromoquinones and enamines with gold(Ⅰ) catalyst.We have developed an efficient method for synthesis of β-enaminones and β-enaminoesters. We start with2-bromonaphthalene-1,4-dione to synthesize bioactive molecules. The effecets of solvents, amount of base and diffferent gold catalysts were discussed, under the optimized conditions, a variety of β-enaminones and β-enaminoesters were screened to evaluate the scope of this reaction. From the results, we clearly see that the substituents of β-enaminones or β-enaminoesters were aromatic properties, the reaction took place very badly when it was aliphatic substituents, the reaction took place very well. In symmary, the application of gold in organic synthesis is further extended, which make it possible to achieve the heterocyclic compounds.Part4. Gold (I) catalyzed synthesis of polysubstituted pyrroles from β-enamino ketones or esters and (E)-1-nitro-2-phenylethylene.Densely substituted pyrroles are an important class of heterocyclic compounds with useful biological and physical properties. the classical methods for the synthesis of pyrroles is Knorr reaction, Hantzsch reaction, and Paal-Knorr condensation reaction. However, some of them usually present significant limitations, such as tedious workup, harsh nature of reaction conditions, low yields, long reaction times. Therefore, the continuous studies for the synthesis of pyrroles in terms of efficient, environmental benign, operational simplicity, economic viability, and high selectivity are still of great significance. we have successfully developed a novel, operationally simple, economical, and environmentally friendly reaction to synthesis functionalized pyrroles by employing β-enaminones (esters) and trans β-nitrostyrene. This method is quite general and it works well with a wide variety of β-enaminones (esters). The major advantage of this method is low catalyst loading (1%mol).更多还原