【作者】 张欣；

【导师】 冯小明；

【作者基本信息】 四川大学 ， 有机化学， 2007， 博士

【摘要】 高烯丙基醇广泛应用于许多天然产物和具有生物活性化合物的合成。羰基化合物的对映选择性烯丙基化反应是制备光学活性的高烯丙基醇的最有效的方法之一。近年来,寻找高效的合成高烯丙基醇的方法已经受到相当大的重视,通过醛的烯丙基化反应来获得烯丙基化产物的方法有了很大的发展,不管是通过金属络合物还是利用小分子来催化,都取得了很大的成功。但是,由于酮具有活性低,空间位阻大和较难与金属键合的特点,所以,开展酮的不对称烯丙基化反应的研究,对化学工作者来说一直是巨大的挑战。氮氧化合物,作为很强的电子给予体,一直在配体设计和合成方面有着重要的地位。和每个硬币都有两面一样,氮氧化合物也主要有两方面的应用。一方面是作为有机小分子催化剂,另一方面就是与金属络合形成金属络合物催化剂。在醛酮亚胺的不对称硅腈化反应中,氮氧化合物作为小分子催化剂取得了巨大成功。但是在形成金属络合物催化剂方面的研究和应用还相当有限。本文致力于酮的不对称烯丙基化反应,利用(S)-哌啶-2-甲酸衍生的酰胺双氮氧化合物和三溴化铟形成的金属铟络合物成功地实现了酮的不对称烯丙基化反应,并取得了很好的收率和对映选择性。设计和合成了新型手性双氮氧配体24个,非手性氮氧3个,手性螺环双醇配体1个,还有一些席弗碱类和氢化席弗碱类配体16个。全部成功地应用于考察酮的不对称烯丙基化反应。在较深入系统地考查了这类配体中基团的电子效应和空间位阻效应后,发现配体52与InBr3以2:1配合制备的络合物对催化酮的烯丙基化反应表现出优秀的不对称诱导能力。经过对中心金属、配体与金属的比例、溶剂、添加剂、催化剂用量、四烯丙基锡的用量、底物浓度和反应温度等反应条件的优化后,确定了最佳反应条件。底物扩展证明,该催化体系对一系列芳香酮具有优良的手性诱导能力,在30 mol%的催化剂用量下获得相应的高烯丙基醇具有很好的对映选择性(高达83%ee)和中等到优秀的收率(高达94%)。经过对实验数据的分析、讨论和对配体52、52与铟形成络合物的~1H NMR谱图的对比,以及非线性效应的考察,提出了包括可能过渡态的催化循环机理。在该体系中, 52和铟形成的络合物是双功能催化剂,其氮氧偶极基团作为Lewis碱活化四烯丙基锡,而络合以后的铟作为Lewis酸来活化酮。这所有的结果都为今后这类手性酰胺双氮氧配体在不对称烯丙基化催化反应中的应用提供了重要的研究基础。更多还原

【Abstract】 The enantioselective allylation of carbonyl compouds is one of the most valuable methods to furnish chiral homoallylic alcohols, which are widely used in the syntheses of many natural products and biologically active compounds. The development of efficient synthetic methods for the preparation of chiral homoallylic alcohols has attracted considerable attention. In recent years, several new procedures with either metal complexes or organocatalysts have been developed to the allylation of aldehydes. However, allylation of ketones is still challenging, due to their reduced reactivities and lower binding affinity to metals.N-oxides, a series of strong electronic donors, have long been recognized as suitable entities for ligand design. As a coin, the application of chiral N-oxides has two sides. One is metal-free catalytic transformations, and the other is as ligands in metal complex catalysts. N,N′-dioxides as a highly efficient organocatalyst have been successfully used in the cyanosilylation of aldehydes, aldimines, ketones and ketoimines. However, use of N-oxides in metal-mediated asymmetric synthesis have been limited.In this dissertation, the efforts were focused on the enantioselective allylation of ketones catalyzed by (S)-pipecolic acid-derived N,N′-dioxides and Indium (III) bromide complexes, which delivered good yields and enantioselectivities. A novel chiral N,N’-dioxide of twenty-four ligands were synthesized, as well as three achiral N-oxides, one chiral (S)-2,2’,3,3’-tetrahydro-1,1’-spiro-bi-[indene]-7,7’-di ol ligand and other sixteen imine and amide ligands. The chiral N,N’-dioxide Indium complexes which were prepared from N,N’-dioxide and InBr3 at the ratio of 2:1 were successfully applied in asymmetric allylation of ketones. The electronic and spatial effects of the substitutes on chiral N,N’-dioxide ligands impacting on the enantioselectivity and reactivity of this reaction were systematically studied. The results revealed that 52-In(III) showed an excellent chiral induction in this reaction. We investigated several factors in detail that affected the enatioselectivity, such as the structure of the ligands (steric and electronic effects), central metal, molar ratio of chiral ligands to InBr3, solvent, concentration of substrate, different amount of catalyst, reaction temperature and so on. Under the optimized conditions, A variety of aromatic ketones were found to be suitable substrates in the presence of 30 mol% 52-In(III) complex, and afforded the corresponding homoallylic alcohols with good enantioselectivites (up to 83% ee) and moderate to high yields (up to 94%).And based on the experimental results, the 1H NMR spectra of the ligand 52 and the 52-In(III) complex and the nonlinear effect for the reaction, a possible catalytic cycle including a transition state has been proposed to explain the origin of the reactivity and asymmetric inductivity, and a bifunctional catalyst was described with Lewis base N-oxide activating tetraallyltin and Lewis acid indium activating ketone. All of these results offer some important reference to asymmetric allylation of carbonyl compounds with chiral N,N’-dioxide ligands systemically investigated in the future.更多还原