【作者】 张亚娟；

【导师】 张攀科； 徐森苗；

【作者基本信息】 郑州大学 ， 有机化学， 2019， 硕士

【摘要】 硅与碳处于同一主族,两者有着相似的价电子结构和成键性质,常作为碳的等电子体使用,再加上其独特的结构和理化性质使得有机硅化合物在材料和合成化学中得到了广泛应用。另一方面,硅原子具有更大的原子半径,更强的正电性,更好的脂溶性以及它本身所具有的低毒性,使得有机硅化合物在药物化学领域具有很高的研究价值。其中,手性α-氨基硅烷由于具有生物活性更是受到了人们的广泛关注。α-氨基硅烷合成方法有很多,但是只有一部分方法用于它的不对称合成。早期的手性α-氨基硅烷的合成用手性辅基和手性试剂的方法,需要用到有机锂试剂,主要通过αzα-brook重排和硅基锂试剂对手性亚胺的加成合成,然而这种策略存在着反应条件苛刻和官能团容忍性差等问题,铜催化的不对称反应很好的解决了早期方法的官能团兼容性差等问题,但是这种方法也存在着一些局限性如醛亚胺、硅基铜亚胺只对芳基底物反应,乙烯基硅烷的氢胺化需要用到昂贵的硅烷作为氢源和不稳定的胺化试剂。另外含有酯基、氰基、酰胺和卤素的底物的不对称催化合成α-氨基硅烷仍在探索阶段。因此,发展温和条件下的高效反应来构建多官能团的手性α-氨基硅烷仍然是这一个领域需要解决的问题。本文在前期人们发展的α,b-不饱和化合物的催化不对称b-硅化的基础上,通过不同的氮原子取代基的选择,发展了一类手性卡宾铜络合物催化的b-酰胺基丙烯腈和b-酰胺基丙烯酸酯类化合物的不对称b-硅化反应。在室温下,以硼基硅烷为硅化试剂,在C2对称的光学纯的二氢咪唑盐卡宾前体(10 mol%)、氯化亚铜(10 mol%)、叔丁醇钠(20 mol%)和甲醇(2当量)的存在下,此类反应在四氢呋喃中能够以良好到优秀的对映选择性ee(84-94%),以最高分离收率可达98%,合成出相应的多官能团的手性α-氨基硅烷,并具有很好的官能团兼容性。更多还原

【Abstract】 Silicon and carbon are in the same main group,so they have similar valence electron structure and bonding properties.They are often used as carbon isoelectronics and their unique structure and physicochemical properties make organosilicon compounds widely used in materials and synthetic chemistry.On the other hand,silicon atoms have a larger atomic radius than carbon,stronger positive charge,better fat solubility and lower toxicity.Organosilane compounds have found widespread applications in synthetic and medicinal chemistry.Among these,chiral ?-aminosilanes have gained increasing attention because they have shown significant bioactivities.Accordingly,many methods have been developed in the synthesis of these structures.However,only a few methods have been reported for their asymmetric synthesis.Tranditonal methods rely on diastereoselective synthesis with involvement of organolithium reagents,which usually suffered from limitations such as narrow functional group tolorence and harsh reaction conditions.Examples inlcude reverse aza-Brook rearrangement and the addition of silyllithium reagents to the chiral aldimines,.On the other hand,elegant copper-catalyzed asymmetric transformations provide mild and straightfoward approaches to access these structures with wide functional group compatibility.However,there are still some limitations.For examples,reactions of aldimines or silyl ketimines are restricted to aryl substrates;hydroamination of vinylsilanes requires expensive silanes as hydride source and instable aminating reagents.In addition,catalytic methods to synthesizing chiral ?-aminosilanes with functional groups such as ester,cyanide,amide and halogens remain virtually unexporlored,which hamper further application of these methods.Thus,it is still appealing to develop effiecient methods to prepare ?-aminosilanes with multiple functionalities.To this end,we herein develop the NHC-copper catalyzed asymmetric conjugate silylation reactions of ?-amido-acrylonitrles and ?-amido-acrylates for the first time in the presence of catalytic amount of chiral N-heterocyclic carbene(NHC)/Copper(I)complex.A varitey of functionalized chiral ?-Aminosilanes were obtained in good yields with high enantioselectivities.更多还原