【作者】 刘冰；

【导师】 吴海虹； 张俊良；

【作者基本信息】 华东师范大学 ， 物理化学， 2019， 博士

【摘要】 不对称催化是当代有机合成化学领域的重要组成部分,是制备光学活性产物最具前景的方法之一。其中,金属络合物不对称催化具有高精准的合成特点,得到了广泛关注。另外,过渡金属铜由于其储量丰富、廉价易得,因此成功地吸引了科研工作者的目光;而手性配体作为催化剂的另一核心成分,理应得到大力的发展。综上,继续发展铜/配体络合物催化的不对称反应仍是当今学界的研究热点。本论文主要进行新型手性联吡啶配体的设计与合成研究;并开展了一系列铜催化缺电子烯烃的不对称反应研究。主要有以下四方面内容:一、新型手性联吡啶配体的设计与合成研究从商业可得的二溴吡啶出发,经过偶联、缩合以及加成等一系列转化得到了含氮手性配体。这类叔丁基亚磺酰胺衍生的手性联吡啶骨架配体具有多个配位点,期待其与不同的金属进行配位,应用在更多的不对称催化反应当中。二、铜催化的手性吡咯衍生物的合成研究首先,使用缺电子烯烃与酮亚胺叶立德作为原料,在铜/(S,S)-’Pr-FOXAP配体的催化下,完成了不对称迈克尔加成/水解环化的过程。通过该反应得到了系列高对映选择性含有连续2个手性中心的吡咯啉衍生物,且具有很好的底物普适性和官能团兼容性。其次,当使用我们组内所发展的Ming-Phos做为配体时,可以调控进行[3+2]环加成过程,完成具有连续3个手性中心的吡咯烷衍生物合成。接着,使用(R)-Tol-BINAP作为配体时,实现了吲哚烯烃与甲亚胺叶立德的[3+2]环加成反应,得到了含有连续4个手性中心的吡咯衍生物。最后,在铜/亚磷酰胺配体催化下,从双膦氧烯烃和甲亚胺叶立德出发,使用[3+2]环加成策略,成功实现了高对映选择性吡咯烷衍生的双膦乙烷(DPPE)型手性配体的合成。三、铜催化缺电子烯烃不对称硼化反应研究该部分反应以β/β-双取代的缺电子烯烃和联硼酸酯为反应原料,在Cu(N03)2·3H20和(S,S)-iPr-FOXAP的催化下,高对映选择性地构筑了含三氟甲基的手性三级硼酸酯。并且通过一锅法完成了手性叔醇的制备,两类产物均以高达99%的产率和99%ee得到。四、铜催化的不对称串联环化合成茚类衍生物的反应研究我们选用铜/手性二茂铁配体作为反应的催化剂,成功地实现了缺电子烯烃与联硼酸酯的不对称共轭加成/Aldol环化反应,高对映选择性地合成了一系列多取代茚类衍生物。更多还原

【Abstract】 Asymmetric catalysis is an important part of contemporary organic synthetic chemistry,and it is one of the most promising methods for preparing optically active products.Among them,the asymmetric catalysis of metal complexes has attracted wide attention of researchers because of its efficient synthesis process.As the earth-aboundant,cheap and easily available metal,the asymmetric reaction of copper catalysis has become one of the important choices for researchers.Therefore,the continued development of new ligands and copper-catalyzed asymmetric reactions remains a hot topic of research today.This dissertation is mainly focous on design and synthesis of novel chiral bipyridine ligands;and a series of asymmetric copper catalyzed reactions of electron-deficient olefins.The specific research contents include the following four aspects:一、Design and synthesis of novel chiral bipyridine ligandsStarting from commercially available dibromopyridine,a series of conversions such as coupling,condensation,and addition provide a new type of tert-butylsulfenamide-derived bipyridine ligand.These chiral ligands have multiple coordination sites,and are expected to have a potential catalytic applications.二、Copper-catalyzed synthesis of chiral pyrrole derivativesFirst,a highly chemo-,diastereo-,and enantioselective Cu(1)/(S,S)-Pr-FOXAP catalyzed Michael addition of ketiminoester to β-trifluoromethyl β,β-disubstituted enones was developed.This method provides a facile access to highly functionalized 1-pyrrolines bearing two contiguous stereocenters,which including a trifluoromethylated all-carbon quaternary stereocenter via one-pot hydrolytic cyclization.In addition,a catalytic asymmetric[3+2]cycloaddition of glycine ketimines with/3-CF3 β,β-disubstituted enones was realized in the presence of a chiral copper(I)/Ming-Phos complex.This method provides an access to construct highly functionalized pyrrolidines bearing three contiguous stereocenters,which including a trifluoromethylated all-carbon quaternary stereocenter.Following,when(R)-Tol-BINAP ligand was used,a cycloaddition of indol-derived electron-deficient olefin with azomethine ylide was achieved.Finally,we provides an efficient access to the chiral cyclic 1,2-bis(diphenylphosphines via asymmetric[3+2]cycloaddition.Both enantiomers of the products can be obtained with good to excellent diastereo-and enantioselectivities:二、Copper-catalyzed asymmetric boronation of electron-deficient olefinsAsymmetric boration of β,β-disubstituted electron-deficient enones and B2Pin2 was development under the catalysis of Cu(NO3)2·3H2O/(S,S)-Pr-FOXAP,furnishing high enantioselective compounds containing quaternary carbon center of CF3 and boron atom.In addition,the preparation of the chiral tertiary alcohol was accomplished by one-pot method.The reaction provides a feasible path for the synthesis of highly enantioselective boron-containing compounds.四、Copper catalyzed asymmetric tandem cyclization to indene DerivativesThis method provides access to multi-substituted indanes holding three consecutive chiral centers via Michael addition/Aldol cyclization.The features of this reaction include high enantioselectivity,easily prepared starting materials,well functional group tolerance and mild reaction conditions.更多还原