有机小分子催化剂介入的不对称交叉脱氢偶联反应研究

项目来源

国家自然科学基金(NSFC)

项目主持人

张俊民

项目受资助机构

深圳大学

项目编号

21402124

立项年度

2014

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

25.00万元

学科

化学科学-合成化学-不对称合成

学科代码

B-B01-B0106

基金类别

青年科学基金项目

关键词

手性产物 ; 交叉脱氢偶联 ; 绿色化学 ; 不对称催化 ; 有机小分子催化剂 ; Organocatalyst ; Cross-dehydrogenative coupling ; Asymmetric catalysis ; Chiral product ; Green chemistry

参与者

韩沛;曹梦梦;吴博超

参与机构

深圳大学

项目标书摘要:利用不对称催化的方法构建有机化合物的手性中心在有机合成、特别是在手性药物合成中起着至关重要的作用。同时,绿色且高效的合成方法的发展也是有机合成领域的一个非常重要的研究方向和目标。交叉脱氢偶联(CDC)是一种有效而且相对清洁的反应策略,因为其在氧化的条件下可以直接实现两个C-H键的偶联,从而避免了原料的预功能化,进而极大地缩短了合成步骤、提高了反应效率。而就目前来说,此类相关的消旋CDC反应已经得到了深入的发展,但是具有挑战性的高对映选择性CDC反应的研究还相对较少,且有待于进一步的开发和利用。另外近年来随着有手性机小分子催化剂的快速发展,有机小分子催化已经成为不对称合成中非常重要的手段之一。本申请项目计划开展有机小分子催化剂介入的新型不对称交叉脱氢偶联反应研究,从而实现相对绿色而有效的新颖手性中心的构建,进而并将其相关方法应用于手性药物以及其它具有生物活性的手性化合物的合成中。

Application Abstract: Asymmetric catalysis approaches to construct chiral centers of organic compounds,play a key important role in organic synthesis,especially in the chiral drug synthesis.While,the development of green effective synthetic methods with atom-economy and shorter synthetic routines is highly desirable in current organic synthesis.The cross-dehydrogenative coupling(CDC)reaction can be an efficient and relatively clean strategy in organic synthesis.The CDC reaction can realize the direct coupling of two C-H bonds,that avoids the pre-functionalization of substrates therefore greatly short the synthetic routines.The racemic CDC reaction has been extensively studied,but the challenging highly enantioselective CDC reaction is scarce,that urgently needs to be further developed.In addition,with the rapid development of chiral organic small molecule catalysts,organocatalysis has been one of the most important tools for asymmetric synthesis.This project will develop the organocatalyst mediated novel asymmetric cross-dehydrogenative coupling reactions to realize the greener and more efficient construction of chiral centers.And the developed methods also will be applied for the synthesis of chiral drugs and other biologically active chiral compounds.

项目受资助省

广东省

项目结题报告(全文)

交叉脱氢偶联(CDC)是一种有效而且相对清洁的反应策略,因为其在氧化的条件下可以直接实现两个C-H键的偶联,从而避免了原料的预功能化,进而极大地缩短了合成步骤、提高了反应效率。本项目主要完成了三个方面的研究成果:(a)我们成功发明了一种新型的有机海绵光催化剂,并成功用于可见光驱动的交叉脱氢偶联反应。具体的,我们将高分子材料科学领域的表面修饰和聚合物刷合成技术应用于有机光催化剂的发展,成功发展了一种简便有效的步骤来制备有机海绵光催化剂,并将有机染料类光催化剂玫瑰红负载于PDMS海绵上。这种海绵光催化剂在可见光的激发下对于交叉脱氢偶联反应显现出卓越的光催化活性。在循环利用15次之后,海绵光催化剂活性并未出现明显降低。通过自制的简单连续流动反应装置能有效地进行克级反应。这些结果表明PDMS海绵是一种具有很好发展前景的固相有机光催化剂载体。(b)另外我们还设计、合成了一种新的双功能有机海绵光催化剂,既有可见光催化的作用,也有有机小分子催化的作用。具体地,选用的载体为聚二甲基硅氧烷(PDMS)海绵,光催化剂为玫瑰红(RB),小分子有机催化剂为脯氨酸(Pro),通过固相合成(SPPS)的技术将三者依次链接。该催化体系能够起到协同催化,并提供疏水微环境的作用,使四氢异喹啉和酮在水相中顺利地发生交叉脱氢偶联(CDC)反应,反应条件温和,收率较高。(c)我们以负载在氧化石墨烯上的钯纳米粒子(PdNPs/GO)作为催化剂,成功发展了第一例非均相导向Csp2−H乙酰氧基化方法学。该方法的实用性在于催化剂制备简单,催化效率高,官能团适应性广和放大量反应容易。热滤试验和Hg(0)毒害实验表明反应为非均相催化机理。此反应从形式上也可以算为脱氢的偶联反应。

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  • 1.Photocatalyst- and transition-metal-free alpha-allylation of N-aryl tetrahydroisoquinolines mediated by visible light

    • 关键词:
    • DONOR-ACCEPTOR COMPLEX; PHOTOREDOX CATALYSIS; CHARGE-TRANSFER;PHOTOCHEMICAL ACTIVITY; ELECTRON-TRANSFER; ALKYLATION; ALDEHYDES;FUNCTIONALIZATION; ALKYNES; DRIVEN
    • Li, Zhuohua;Ma, Pengju;Tan, Yongzhu;Liu, Yufei;Gao, Min;Zhang, Yujun;Yang, Bo;Huang, Xuan;Gao, Yuan;Zhang, Junmin
    • 《GREEN CHEMISTRY》
    • 2020年
    • 22卷
    • 3期
    • 期刊

    A convenient and efficient alpha-allylation of N-aryl tetrahydroisoquinolines has been achieved. This transformation can be realized under only visible light irradiation without the aid of transition metals or photocatalysts. The mechanism involves a novel in situ-generated electron-donor-acceptor (EDA) complex between the N-aryl tetrahydroisoquinolines and an allyl or a benzyl bromide. Irradiation with purple light triggered single-electron transfer (SET) from the N-aryl tetrahydroisoquinolines to the allyl or benzyl bromide of the EDA complex, inducing the formation of the corresponding allyl or benzyl radical and the subsequent radical-radical coupling. This approach represents the first example of a photocatalyst- and transition-metal-free alpha-allylic and benzylic functionalization of N-aryl tetrahydroisoquinolines.

    ...
  • 2.Photocatalyst- And transition-metal-free α-allylation of: N -aryl tetrahydroisoquinolines mediated by visible light

    • 关键词:
    • Allylation;Free radical reactions;Irradiation;Light;Allyl bromide;Allyl radicals;Benzyl bromide;Electron donor acceptor complex;Metal free;Purple lights;Single electron transfer;Tetrahydroisoquinolines;Visible light;Visible-light irradiation
    • Li, Zhuohua;Ma, Pengju;Tan, Yongzhu;Liu, Yufei;Gao, Min;Zhang, Yujun;Yang, Bo;Huang, Xuan;Gao, Yuan;Zhang, Junmin
    • 《Green Chemistry》
    • 2020年
    • 22卷
    • 3期
    • 期刊

    A convenient and efficient α-allylation of N-aryl tetrahydroisoquinolines has been achieved. This transformation can be realized under only visible light irradiation without the aid of transition metals or photocatalysts. The mechanism involves a novel in situ-generated electron-donor-acceptor (EDA) complex between the N-aryl tetrahydroisoquinolines and an allyl or a benzyl bromide. Irradiation with purple light triggered single-electron transfer (SET) from the N-aryl tetrahydroisoquinolines to the allyl or benzyl bromide of the EDA complex, inducing the formation of the corresponding allyl or benzyl radical and the subsequent radical-radical coupling. This approach represents the first example of a photocatalyst- and transition-metal-free α-allylic and benzylic functionalization of N-aryl tetrahydroisoquinolines. This journal is © The Royal Society of Chemistry.

    ...
  • 3.Organic Cotton Photocatalysis

    • 关键词:
    • Cotton; Supported catalysts; Visible light photocatalysis;Cross-dehydrogenative coupling; N-Demethylation;DEHYDROGENATIVE COUPLING REACTIONS; LIGHT PHOTOREDOX CATALYSIS; MODIFIEDCARBON NITRIDE; VISIBLE-LIGHT; TERTIARY-AMINES; MANNICH REACTION;SYNTHETIC APPLICATIONS; METAL-COMPLEXES; BOND FORMATION; OXIDATION
    • Xiao, Liuqing;Huang, Yuxing;Luo, Yu;Yang, Bo;Liu, Yizhen;Zhou, Xuechang;Zhang, Junmin
    • 《ACS SUSTAINABLE CHEMISTRY & ENGINEERING》
    • 2018年
    • 6卷
    • 11期
    • 期刊

    Cotton fiber is an abundant natural material, which has a long history of application in human daily life. However, a report on using such material in catalysis for organic synthesis is rare. We envisaged that the hydroxyl groups on the surface of cotton fiber could be utilized for functionalization and further immobilization of organic catalysts. In this report, we demonstrate the facile functionalization of cotton fiber by growing polymer brushes on its surface and further anchoring of Rose Bengal (RB) organic photocatalyst. This novel composite cotton photocatalyst demonstrated high efficiency in catalyzing cross-dehydrogenative coupling reactions and N-demethylation reactions with irradiation of visible light. The catalytic reaction can be facilely scaled up by a homemade circulating flow reactor.

    ...
  • 4.Polydimethylsiloxane sponge supported DMAP on polymer brushes: Highly efficient recyclable base catalyst and ligand in water

    • 关键词:
    • PDMS sponge; Supported catalysts; DMAP; Base catalyst; Ligand; In water;METAL-ORGANIC FRAMEWORKS; MULTICOMPONENT REACTIONS; HETEROGENEOUSCATALYSTS; CRYSTAL-STRUCTURES; MESOPOROUS SILICA; ACID CATALYSTS;LEWIS-ACIDS; GRAPHENE; NANOPARTICLES; GREEN
    • Luo, Yu;Xie, Weiwei;Huang, Yuxing;Zhang, Teng;Yang, Bo;Liu, Yizhen;Zhou, Xuechang;Zhang, Junmin
    • 《JOURNAL OF CATALYSIS》
    • 2018年
    • 367卷
    • 期刊

    The successfully developed polydimethylsiloxane (PDMS, a stable hydrophobic polymer material) sponge supported DMAP can be used as base catalyst and ligand to facilitate a series of organic transformations with high efficiency and good reusability in water. This PDMS sponge DMAP can provide much better catalytic activities and selectivities than free DMAP in water. Through an easy-to-build continuous flow reactor, the PDMS sponge DMAP facilitated reactions can be facilely scaled up. This porous hydrophobic PDMS sponge material will be a promising carrier for the development of highly efficient recyclable catalysts in water. (C) 2018 Elsevier Inc. All rights reserved.

    ...
  • 5.Polydimethylsiloxane Sponge-Supported Nanometer Gold: Highly Efficient Recyclable Catalyst for Cross-Dehydrogenative Coupling in Water.

    • 关键词:
    • CC coupling; amines; dehydrogenation; gold; heterogeneous catalysis
    • Liang, Weiwei;Zhang, Teng;Liu, Yufei;Huang, Yuxing;Liu, Zhipeng;Liu, Yizhen;Yang, Bo;Zhou, Xuechang;Zhang, Junmin
    • 《ChemSusChem》
    • 2018年
    • 11卷
    • 20期
    • 期刊

    Polydimethylsiloxane (PDMS, a stable hydrophobic polymer material) sponge-supported nanometer-sized gold can be used as a highly efficient recyclable catalyst for cross-dehydrogenative coupling of tertiary amines with various nucleophiles in water. This PDMS sponge nanometer gold catalyst can provide much better activity than the free nanometer gold in water. The reaction can be scaled up by using an easy-to-build continuous flow reactor. These results indicate the potential application of porous hydrophobic PDMS sponge material as a promising support for highly efficient recyclable catalysts in water. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

    ...
  • 6.Spectroscopic studies of chiral perovskite nanocrystals

    • 关键词:
    • Perovskite ; Surface defects ; Dichroism ; Spectroscopic analysis ; Ligands ; Stereochemistry;Anisotropy factor ; Chiroptical properties ; Circular dichroism spectra ; Electronic interactions ; Optically active material ; Semiconductor nanocrystals ; Spectroscopic studies ; Surface distortion
    • HeTingchao;LiJunzi;LiXingrong;RenCan;LuoYu;ZhaoFenghuan;ChenRui;LinXiaodong;ZhangJunmin
    • 《Applied Physics Letters》
    • 2017年
    • 111卷
    • 15期
    • 期刊

    As an emerging type of optically active material, semiconductor nanocrystals (NCs) stabilized by chiral molecules have attracted much attention. Owing to the wide range of potential applications of chiral perovskite NCs, the development of these materials is of great importance, but there has been a lack of relevant studies. Here, we describe an investigation of the properties of chiral perovskite NCs obtained using post-synthetic ligand exchange (achiral ligand/chiral ligand). These are found to exhibit mirror-image circular dichroism spectra. It is the chirality of the ligand (enantiomeric 1,2-diaminocyclohexane, DACH) that is most likely responsible for the induction of chiroptical activity in these NCs. Furthermore, their chiroptical properties and the corresponding mechanisms are found to depend strongly on the amount of capping ligand. When excess DACH is used to cap the surface of the NCs, their chiroptical properties are induced mainly by aggregation of DACH on the surface in a chiral pattern. In contrast, when small amounts of DACH are used for the capping, it is mainly surface distortion (or defects) and electronic interaction mechanisms that contribute to the chiroptical behavior of the NCs. In both cases, the anisotropy factors of the NCs are of the order of 10-3, which is comparable to or larger than the values reported for other chiral semiconductor and metal NCs. This work opens the door toward further understanding of chiroptical perovskite NCs and their potential applications. © 2017 Author(s).

    ...
  • 7.Design and chiroptical properties of a water-soluble and violet-blue emissive alkyne template

    • 关键词:
    • Alkyne architecture; Circular dichroism; Circular polarizedluminescence; Two-photon circular dichroism;CIRCULARLY-POLARIZED LUMINESCENCE; ENANTIOSELECTIVE SYNTHESIS;PHOTOPHYSICAL PROPERTIES; MULTIPHOTON ABSORPTION; CONJUGATED POLYMERS;2-PHOTON ABSORPTION; SOLVENT; DICHROISM; FLUORESCENCE; AGGREGATION
    • He, Tingchao;Zhang, Yi;Yao, Song;Li, Xingrong;Zhao, Fenghuan;Lin, Xiaodong;Xia, Jiuxu;Lu, Wei;Ye, Chuanxiang;Chen, Rui;Zhang, Junmin
    • 《SYNTHETIC METALS》
    • 2017年
    • 234卷
    • 期刊

    Circular dichroism (CD) and circular polarized luminescence (CPL) are useful for various applications. However, it is difficult to achieve excellent CD and CPL in differently polar solvents simultaneously. This work provides a simple but efficient way to construct violet-blue fluorescent and water-soluble chromophore through the construction of rigid conformation of the alkyne architecture. By introducing proline pendants into alkyne architecture, the chromophore exhibits reasonable CD and CPL properties in the lowly and highly polar solvents. More importantly, even in water, the chromophore displays effective CD anisotropy factor (g(abs) similar to 1 x 10(-3)) and luminescence dissymmetry factor (g(lum) similar to 2 x 10(-3)), as well as high fluorescence quantum yield (Phi up to 35%). Additionally, the chromophore exhibits large two-photon CD according to the theoretically calculated results. The excellent chiroptical properties from the simple organic fluorophore enables its future applications in miniatured optoelectronic devices and CPL-based bioimaging.

    ...
  • 8.Microfluidic Patterning of Metal Structures for Flexible Conductors by In Situ Polymer-Assisted Electroless Deposition

    • 关键词:
    • ORGANIC SOLAR-CELLS; STRETCHABLE ELECTRONICS; VAPOR-DEPOSITION;FABRICATION; ULTRATHIN; DEVICES; DESIGN; YARNS
    • Liang, Suqing;Li, Yaoyao;Zhou, Tingjiao;Yang, Jinbin;Zhou, Xiaohu;Zhu, Taipeng;Huang, Junqiao;Zhu, Julie;Zhu, Deyong;Liu, Yizhen;He, Chuanxin;Zhang, Junmin;Zhou, Xuechang
    • 《ADVANCED SCIENCE》
    • 2017年
    • 4卷
    • 2期
    • 期刊
  • 9.An Efficient Synthesis of Tetracyclic Pyrano[ 2,3-d]pyrimidines

    • 《JOURNAL OF HETEROCYCLIC CHEMISTRY》
    • 2017年
    • 54卷
    • 1期
    • 期刊

    [GRAPHICS]A series of pyrano[ 2,3-d] pyrimidine derivatives have been synthesized by the reaction of 2-amino-3cyano- 4H-pyrans and acetic anhydride with acid catalyst. This method is very efficient because of short reaction times and easy work- up, and it provides an efficient and promising synthetic strategy for the construction of the tetracyclic pyrano[ 2,3-d] pyrimidine skeleton. The X-ray crystal structures of products are confirmed, and the possible mechanism is provided in this paper.

    ...
  • 10.A DNA kinetics competition strategy of hybridization chain reaction for molecular information processing circuit construction

    • 关键词:
    • STRAND DISPLACEMENT CASCADES; SIGNAL AMPLIFICATION; ENZYME-FREE;ISOTHERMAL AMPLIFICATION; LOGIC-CIRCUITS; NANOSTRUCTURE; COMPUTATION;PROBES; CELLS; BIOSENSORS
    • Tang, Weiyang;Huang, Qichen;Yang, Zhenjie;Zheng, Qiwei;Wang, Lihong;Zhang, Junmin;Chen, Liang;Zhou, Xuechang;Liu, Yizhen;Hu, Jiming
    • 《CHEMICAL COMMUNICATIONS》
    • 2017年
    • 53卷
    • 11期
    • 期刊

    Herein we propose a hybridization chain reaction based kinetics competition strategy able to recognize the combination/sequence of input signals. Further, a DNA priority encoder and a keypad lock were constructed. This strategy allowed us to develop a one-pot assay that can automatically and smartly respond to multiple inputs.

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