【作者】 何玉萍；

【导师】 龚流柱；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2014， 博士

【摘要】 C-H键的直接官能化反应为结构复杂多样的有机化合物提供了一种更为高效的合成方法,因此它一直是有机化学界研究的热点和难点,也吸引着越来越多化学家的关注。本论文主要研究了手性布朗斯特酸和过渡金属催化的的sp3、sp2C-H官能化反应,合成了一系列手性含氮杂环化合物。我们发现手性磷酸可以很好的实现与氮相邻的sp3C-H的不对称官能化反应。在磷酸的催化作用下,α-酮酸酯和芳香胺首先脱水形成亚胺,之后经历[1,5]-氢迁移／关环反应,形成一系列的缩醛胺类化合物。实验过程中发现双磷酸能够很好的催化该反应,对各种底物都能得到较好的结果,能够得到高达90%的收率和86%的对映选择性。我们将金属催化剂和有机小分子多催化剂的体系成功运用到C-H官能化的反应中,实现了以前运用单一催化剂无法完成的反应,而且符合绿色化学中“原子经济性”的概念。我们成功实现了金配合物与布朗斯特酸接力催化的不活泼炔类化合物的[1,5]-氢迁移反应。在金和三氟甲磺酸的接力催化作用下,3-烯烃-1-炔类化合物分别经历氢胺化／还原反应以高达99%收率和95/5的非对映选择性得到一系列的环状缩醛胺类化合物。研究还发现运用手性磷酸可以实现该反应的不对称催化。通过加大手性磷酸的量至200mol%,可以得到高达99%对映选择性的产物。我们发现钯(Ⅱ)／手性配体／手性磷酸能够很好地兼容,并可以很好地实现烯烃的不对称官能化反应。在多催化剂的催化作用下N-(2,2-二苯基己-5-烯-1-基)丙烯酰胺类化合物发生不对称的氧化串联环化反应,可以一步直接构建6,5-双环含氮杂环化合物,并得到中等的收率和很高的对映选择性。通过动力学研究可以发现钯(Ⅱ)配合物与手性磷酸存在协同效应。手性配体和阴离子共同控制产物的立体选择性。更多还原

【Abstract】 Direct functionalization of C-H bonds has been a research topic that has been receiving increasing interest in organic chemistry because it provides a strategically new opportunity for the creation of structurally complex and diverse organic molecules. In this dissertation, we have developed several sp3and sp2C-H functionalization reactions catalyzed by Br(?)nsted acid and transition metal and furnished a serious of nitrogen-containing heterocyclic compounds.We have disclosed that chiral phosphoric acid could fulfill sp3C-H adjacent to nitrogen functionlization well. The reaction proceeds initially with the condensation of o-aminobenzoketone with aniline in the presence of a chiral Br(?)nsted acid to generate an iminium species, which is presumably able to undergo an asymmetric1,5-hydride shift process and a subsequent ring closing reaction to give a cyclic aminal. Bisphosphoric acid showed much better stereoselectivity than other PA and gave cyclic aminals in fairly good diastereo-and enantioselectivities.We have successfully applied muti-catalysts system with metal catalysts and organocatalysts to C-H functionalization reactions which could not complete well using single catalyst previous. This was also in accordance with the concept of "atom economic" in green chemistrywe have developed a relay catalytic hydroamination/redox reaction, which is able to directly assemble the tertiary amine-substituted3-en-1-ynes derivatives and various amines into cyclic aminals in excellent yields (up to99%) and moderate to high diastereoselectivities (up to95/5dr) by using gold(I) complex and trifluoromethanesulfonic acid as the combined catalyst. This method provides an alternative strategy to make the unactivated alkynes undergo the1,5-hydride transfer redox reaction. The enantioselective variant of this process has been realized by using excess amounts of chiral BINOL-derived phosphoric acid capable of delivering the corresponding products with up to99%ee. we have demonstrated that the combined use of a palladium(II) complex of chiral Bu-QUOX ligand and a chiral phosphoric acid enabled a highly enantioselective oxi-dative cascade cyclization reaction of N-(2,2-disubstituted hex-5-en-1-yl)acrylamides, providing a straightforward method to access chiral6,5-bicyclic nitrogeneous hetero-cycles in moderate to good yields and with excellent enantioselectivities. A synergistic effect between the palladium(II) complex and the chiral phosphoric acid was found in the catalysis. The chiral ligand and anion cooperatively control the stereoselectivity.更多还原