手性布朗斯特酸催化不对称环化反应的研究进展

综述了近年来利用多种手性布朗斯特酸催化的Aza Diels-Alder反应、Pictet-Spengler 反应、Nazarov 反应、1,3偶极环加成反应、多组分及串联反应构建手性环状分子的研究进展.参考文献38篇.     

酸促进2-乙烯基苯胺与重氮的[5+1]环化合成2-芳基喹啉

利用廉价易得的2-乙烯基苯胺与重氮化合物在三氟乙酸催化下发生[5+1]环化反应, 以中等至良好的产率合成了24种2-芳基喹啉衍生物. 该方法无需金属催化剂, 官能团兼容性好, 反应成本低, 不仅拓展了重氮化合物参与的新型有机反应, 同时也为2-芳基取代喹啉的合成提供了高效、 经济且简洁的新方法.     

水介质中1,4-二芳基喹啉-2,5-二酮衍生物的绿色合成

以芳醛、3-芳氨基-5,5-二甲基环己-2-烯酮和Meldrum酸为原料, 以水为溶剂, 在回流条件下以三乙基苄基氯化铵为催化剂通过三组分一步反应, 合成了一系列的7,7-二甲基-1,4-二芳基-1,2,3,4,5,6,7,8-八氢化喹啉-2,5-二酮衍生物. 该方法具有中性反应条件、产率高(80 %～92 %)、操作简单和环境友好等优点.     

2-苄基-1,3-二氢-4-异喹啉酮及其衍生物的合成

本文合成了2-苄基-1,3-二氢-4-异喹啉酮的四种3-位亚甲基取代衍生物，四种氧酰基肟和两种6-苄基-5H-异喹啉并[4,3-b]喹啉衍生物。新化合物的结构经元素分析、红外光谱、核磁共振谱证实。     

手性1-芳基四氢异喹啉类衍生物的合成新方法

以1,2,3,4-四氢异喹啉为原料,先依次与二碳酸二叔丁酯、亚氯酸钠反应得到N-Boc-1,2,3,4-四氢-1-异喹啉酮,再和芳基格氏试剂反应得到分子内不对称还原胺化反应的底物,最后以ax-Josiphos为手性配体,[Ir(COD)Cl]₂为金属前体,在Ti(OⁱPr)₄和40%HBr溶液组成的催化体系中合成了8个手性1-芳基四氢异喹啉类化合物,其结构经¹H NMR和¹³C NMR表征。该路线提供了一种以廉价1,2,3,4-四氢异喹啉为原料高效合成手性1-芳基四氢异喹啉类衍生物的新方法,为索利那新等药物的合成提供了新路径。      

芳基喹啉取代螺二芴化合物的合成

2-溴联苯格式试剂与9-芴酮生成的叔醇中间体在酸性条件下环合形成螺二芴,再经Friedel-Crafts酰基化得到2-乙酰基螺二芴(3)和2,2-二乙酰基螺二芴(4);3或4与2-氨基二苯甲酮衍生物在酸催化下经过Friedlander缩合,制备了一系列具有荧光性的2-(4-取代苯基)喹啉-9,9'-螺二芴或2,2'-二(4-取代苯基)喹啉-9,9'-螺二芴,其结构经UV-vis,荧光光谱,1H NMR和元素分析表征.     

Cu2-MnO_x高效催化1,2,3,4-四氢喹啉氧化脱氢芳构化

采用新型无模板草酸盐路线制备了系列不同Cu含量的MnO_x催化剂(MnO_x、Cu1-MnO_x、Cu2-MnO_x、Cu3-MnO_x、Cu4-MnO_x、Cu2-450及Cu2-550),并应用于1,2,3,4-四氢喹啉(THQL)氧化脱氢芳构化。通过热重和热流分析(TG-DSC)、X射线衍射(XRD)、N2物理吸附-脱附、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、能谱(EDS)、X射线光电子能谱(XPS)、H2程序升温还原(H2-TPR)、原子吸收光谱(AAS)手段对催化剂进行表征。结果显示在这七种锰氧化物中,Cu2-MnO_x具有高比表面积、增大的介孔平均孔径、较低的还原温度、最高的Mn~(3+)含量和吸附氧含量,最高的Mn~(3+)/Mn~(4+)。Cu2-MnO_x在温和的反应条件下,以廉价的空气为氧化剂、无碱添加剂的情况下对THQL芳构化转化率和喹啉(QL)选择性分别达99.1%、97.2%。催化剂套用五次后转化率还可达95.8%,选择性随着套用次数增加略有降低,这可能是Cu元素的流失所致。催化剂无定型结构、Mn~(3+)和吸附氧含量,Mn~(3+)/Mn~(4+)、晶格氧的流动性及CuO和MnO_x的协同作用是高催化活性的关键因素。     

铜催化苯甲酰胺有氧环化合成7-叔烷基异喹啉二酮

发展了一种高效、简单的铜/空气催化体系催化的苯甲酰胺串联自由基环化合成7-叔烷基异喹啉二酮的反应。 在廉价CuI存在下,空气环境中,N-烷基-N-甲基丙烯酰基苯甲酰胺与AIBN发生串联自由基加成/环化/碳碳偶联反应,以52%~73%的产率合成了一系列的7-取代异喹啉二酮。 此研究为合成具有潜在药用价值的含氰取代异喹啉二酮提供了一条快速、简单、温和的构建途径。     

R和S-1-(3′-溴-4′-甲氧基)苄基-2-甲基-6-甲氧基-7-羟基-1,2,3,4-四氢异喹啉的合成

单醚链和双醚链的节基四氢异喹啉在生物碱中较为长见。一般合成这类四氢异喹啉,是合成在一定位置上有溴的四氢异喹啉,然后与另一含羟基的四氢异喹啉通过Ullmann反应     

水相中2-氨基-4-芳基-5,6-二氢化-4H-吡喃并[3,2-c]喹啉-5-酮衍生物的合成

以芳亚甲基丙二腈或2-氰基-3-芳基丙烯酸酯和4-羟基喹啉-2-酮为原料, 水为溶剂, 在TEBA(三乙基苄基氯化铵)催化下90 ℃, 合成了2-氨基-4-芳基-5,6-二氢化-4H-吡喃[3,2-c]喹啉-5-酮衍生物. 和其它方法相比, 该反应具有反应条件温和, 产率高(87%～96%)和环境友好等优点. 产物的结构通过熔点, IR, ¹H NMR和元素分析表征. 化合物3m的结构通过X单晶衍射分析确证.     

Construction of Axially Chiral Compounds via Central‐to‐Axial Chirality Conversion

Central‐to‐axial chirality conversion represents a fascinating class of chemical processes consisting of the destruction of stereogenic centers and the simultaneous installation of axial chiral elements, which provides efficient methods for the preparation of axially chiral compounds. Using the strategy, a wide range of axially chiral compounds, including biaryls, heterobiaryls, aromatic amides, allenes and vinyl arenes, have been synthesized with high efficiency and excellent enantioselectivity. In addition, central‐to‐axial chirality conversion strategy has been applied to the synthesis of natural products. The strategy has undoubtedly become and will continue to be a hot research topic in the field of asymmetric catalysis and synthesis. In this minireview, we selected some examples to introduce the developments and trends in the central‐to‐axial chirality conversion strategy up to April 2020.     

Construction of Axially Chiral Arylpyrroles via Atroposelective Diyne Cyclization

Axially chiral biaryls widely exist in natural products and pharmaceuticals and are used as chiral ligands and catalysts in asymmetric synthesis. Compared to the well-established axially chiral 6-membered biaryl skeletons, examples of 5-membered biaryls have been quite scarce, and mono-substituted 3-arylpyrrole atropisomers have not been reported. Here, we disclose a copper-catalyzed atroposelective diyne cyclization for the construction of a range of axially chiral arylpyrrole biaryls in good to excellent yields with generally excellent enantioselectivities via oxidation and X−H insertion of vinyl cations. Importantly, this protocol not only represents the first synthesis of mono-substituted 3-arylpyrrole atropisomers, but also constitutes the first example of atroposelective diyne cyclization and the first atropisomer construction via vinyl cations. Theoretical calculations further support the mechanism of vinyl cation-involved cyclization and elucidate the origin of enantioselectivity.     

手性氨基醇诱导联苯构象转化制备轴手性联苯化合物

在(S)-氨基丙醇及(R)-氨基丙醇手性臂的作用下, (M/P)-4,4'-二甲氧基-5,6,5',6'-二次甲二氧基-2-甲酸酯-2'-甲酰氨联苯经构型转化, 制备了光学纯轴手性联苯化合物(P, S)-3a 和(M, R)-3a. 测定了(P, S)-3a 的晶体结构及CD 光谱. 结果表明, 化合物(P, S)-3a 晶体属单斜晶系, P2(1)空间群, 晶胞参数为a＝12.122(2) Å, b＝8.9911(18) Å, c＝12.779(3) Å, β＝112.38(3)°, 在晶体中存在两组分子间氢键相互作用, 一组氢键由羟基氢与另一分子酰胺基团的羰基氧组成O-H…O,另一组由酰胺基团的NH 与另一分子酰胺基团的羰基氧构成N-H…O, 每一分子通过四个氢键与另外两个分子相连,构成棒状结构. 由CD 光谱确定了(M, R)-3b 的立体构型. 此外, 由(P, S)-3a 合成了轴手性化合物(P)-2,2'-二羟甲基-4,4'-二甲氧基-5,6,5',6'-二亚甲二氧基-联苯(6a).     

Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Compounds Involving Indole Derivatives

Indoles are one of the most ubiquitous subclass of N-heterocycles and are increasingly incorporated to design new axially chiral scaffolds. The rich profile of reactivity and N−H functionality allow chemical derivatization for enhanced medicinal, material and catalytic properties. Although asymmetric C−C coupling of two arenes gives the most direct access of axially chiral biaryl scaffolds, this chemistry has been the remit of metal catalysis and works efficiently on limited substrates. Our group has devoted special interest in devising novel organocatalytic arylation reactions to fabricate biaryl atropisomers. In this realm, indoles and derivatives have been reliably used as the arylation partners in combination with azoarenes, nitrosonapthalenes and quinone derivatives. Their efficient interaction with chiral phosphoric acid catalyst as well as the tunability of electronics and sterics have enabled excellent control of stereo-, chemo- and regioselectivity to furnish diverse scaffolds. In addition, indoles could act as nucleophiles in desymmetrization of 1,2,4-triazole-3,5-diones. This account provides a succinct illustration of these developments.     

Enantioselective Construction of Axially Chiral Amino Sulfide Vinyl Arenes by Chiral Sulfide‐Catalyzed Electrophilic Carbothiolation of Alkynes

The enantioselective construction of axially chiral compounds by electrophilic carbothiolation of alkynes is disclosed for the first time. This enantioselective transformation is enabled by the use of a Ts‐protected bifunctional sulfide catalyst and Ms‐protected ortho‐alkynylaryl amines (Ts=tosyl; Ms=mesyl). Both electrophilic arylthiolating and electrophilic trifluoromethylthiolating reagents are suitable for this reaction. The obtained products of axially chiral vinyl–aryl amino sulfides can be easily converted into biaryl amino sulfides, biaryl amino sulfoxides, biaryl amines, vinyl–aryl amines, and other valuable difunctionalized compounds.     

Advances in Atroposelectively De Novo Synthesis of Axially Chiral Heterobiaryl Scaffolds

Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.     

Rhodium-Catalyzed Atroposelective Access to Axially Chiral Olefins via C−H Bond Activation and Directing Group Migration

Axially chiral open-chain olefins represent an underexplored class of chiral platform. In this report, two classes of tetrasubstituted axially chiral acyclic olefins have been accessed in excellent enantioselectivity and regioselectivity via C?H activation of (hetero)arenes assisted by a migratable directing group en route to coupling with sterically hindered alkynes. The coupling of indoles bearing an N-aminocarbonyl directing group afforded C–N axially chiral acrylamides with the assistance of a racemic zinc carboxylate additive. DFT studies suggest a β-nitrogen elimination–reinsertion pathway for the directing group migration. Meanwhile, the employment of N-phenoxycarboxamide delivered C?C axially chiral enamides via migration of the oxidizing directing group. Experiments suggest that in both cases the (hetero)arene substrate adopts a well-defined orientation during the C?H activation, which in turn determines the disposition of the alkyne in migratory insertion. Synthetic applications of representative chiral olefins are demonstrated.     

手性磷酸催化剂在不对称合成中的应用

手性磷酸是2004年报道的一类具有新型结构的强酸性Bronsted酸催化剂,近几年来的研究取得了很大的进展,已经成为有机小分子催化剂的一个重要分支。手性磷酸在催化一系列亚胺的加成和还原反应比如Mannich、亚胺的氢转移、亚胺的膦酰化、Pictet-Spengler、 Strecker、aza-Diels-Alder、 Friedel-Craft和α-重氮酯的烷基化等反应时都表现出了非常好的催化活性和立体选择性。本文主要综述了手性磷酸催化剂应用于亚胺相关反应的研究进展。     

Axially Chiral TADF‐Active Enantiomers Designed for Efficient Blue Circularly Polarized Electroluminescence

The use of a chiral, emitting skeleton for axially chiral enantiomers showing activity in thermally activated delayed fluorescence (TADF) with circularly polarized electroluminescence (CPEL) is proposed. A pair of chiral stable enantiomers, (?)‐(S)‐Cz‐Ax‐CN and (+)‐(R)‐Cz‐Ax‐CN, was designed and synthesized. The enantiomers, both exhibiting intramolecular π‐conjugated charge transfer (CT) and spatial CT, show TADF activities with a small singlet–triplet energy difference (ΔE_ST) of 0.029 eV and mirror‐image circularly polarized luminescence (CPL) activities with large g_lum values. Notably, CP‐OLEDs based on the enantiomers feature blue electroluminescence centered at 468 nm with external quantum efficiencies (EQEs) of 12.5 and 12.7 %, and also show intense CPEL with g_EL values of ?1.2×10^?2 and +1.4×10^?2, respectively. These are the first CP‐OLEDs based on TADF‐active enantiomers with efficient blue CPEL.     

铜/手性磷酸催化烯烃不对称自由基胺芳基化

含β-芳基/α-季碳中心的吡咯烷是一类重要的手性吡咯烷类化合物.目前该类化合物的不对称合成主要是通过钯催化含氮烯烃底物与各类芳基前体的不对称胺芳基化反应来实现的.在这里报道了一种反应机理不同于上述反应的不对称胺芳基化新方法.利用本课题组之前发展的一价铜/手性磷酸组成的金属手性阴离子单电子催化体系成功实现了含氮烯烃底物与芳基重氮盐的不对称自由基的胺芳基化反应,以中等收率和中等至良好的对映选择性得到含β-芳基/α-季碳中心的吡咯烷类化合物.