碘作用下吲哚3位硫醚化反应

本文发展了碘作用下吲哚及其衍生物与芳香族硫醇类化合物的直接硫醚化反应,在吲哚3位形成C-S键。在温和的反应条件下,多种杂环硫醇能够与吲哚反应高产率地得到3位硫醚化合物。     

碘催化下磺酰肼对吲哚的区域选择性硫醚化反应

吲哚存在于很多生物活性分子中,其衍生化受到高度关注.对吲哚的硫醚化可以生成一类重要的生物活性分子,出现过硫基氯、硫醇、二硫化物、锍盐、磺酰氯等硫醚化试剂,但存在对空气敏感、遇水分解、气味恶臭或价格昂贵等缺点,而且在反应中常需过量使用,适用底物的范围小,生成的副产物对环境不友好.中国科学技术大学化学     

以7-氮杂吲哚为内在导向基团的N-芳基C—H官能化研究进展（英文）

内在导向基团是底物中固有的官能团,同时也是产物中的核心结构单元.因此,在C—H官能化反应中,内在导向基团无需事先引入以及事后脱除.在过渡金属催化的N-芳基-7-氮杂吲哚的N-芳基C—H官能化反应中,7-氮杂吲哚往往作为内在的导向基团,借助C—H官能化的反应策略,在N-芳基的邻位引入各种官能团.对过渡金属催化7-氮杂吲哚作为内在导向基的N-芳基C—H官能化的最新研究进展进行了概述.     

5-氮杂吲哚的合成工艺研究

本文以3-甲基-4-硝基氮氧化吡啶为起始原料,经两步反应合成5-氮杂吲哚。通过单因素实验法研究了温度、N,N-二甲基甲酰胺(DMF)、N,N-二甲基甲酰胺二甲缩醛(DMA)、铁粉等因素对反应的影响。较佳工艺条件下,产品按3-甲基-4-硝基吡啶氮氧化物计总收率为88.57%,较文献[1,2]提高了6%。通过熔点测定、1H NMR对最终产物进行了结构表征。此工艺的优点在于操作简单,反应时间短,成本低,收率高,适合于工业化生产。     

吲哚与含CF3氮杂对亚甲基苯醌的1,6-共轭加成反应合成含CF3的吲哚衍生物

以5 mol%布朗斯特酸(±)-BNPA为催化剂，含CF₃氮杂对亚甲基苯醌与吲哚为原料，通过1,6-共轭加成反应合成了7个结构新颖的含CF₃的吲哚类化合物，收率80%~87%，其结构经¹H NMR， ¹³C NMR， ¹⁹F NMR和HR-MS(ESI)表征，并对反应机理进行了探讨。     

壳聚糖@铜催化吲哚与硫粉和芳基碘化物的C3-硫醚化反应

针对以硫单质为硫源的吲哚环中C—S键构筑中催化剂无法回收的问题,制备了2-吡啶甲酸改性壳聚糖(PACS)负载不同类型铜的催化剂,用于催化吲哚、硫粉和碘苯三组分反应一锅法制备C-3位硫醚基吲哚,反应收率高达92%,底物适用性良好.对催化效果最佳的催化剂(PACS@Cu(OAc)₂)进行了热重分析(TGA)、扫描电子显微镜(SEM)、X射线光电子能谱(XPS)等表征与分析,结果表明该催化剂具有不需额外添加配体、易于分离回收及可重复使用的优点.     

碘催化烯烃双官能团化反应制备β-羟基硫醚

室温下,以碘单质为催化剂,以空气为氧化剂,以乙腈水溶液为反应溶剂, 烯烃和硫代磺酸酯反应生成β-羟基硫醚化合物3a~3x（3i, 3k, 3r, 3s为新化合物）,采用¹H NMR,¹³C NMR,MS(ESI)和元素分析对其结构进行确证。以S-(4-氯苯基)-4-氯硫代苯磺酸酯(1)和苯乙烯(2)的反应为模板,对反应条件进行优化。结果表明：最佳反应条件为：S-(4-氯苯基)-4-氯硫代苯磺酸酯 0.5 mmol,苯乙烯1 mmol,催化剂碘用量为0.1 mmol,乙腈1.5 mL,去离子水0.5 mL,室温下反应2 h,收率可达82%。     

区域选择性Michael/Aldol串联反应合成新型1′-茚醇拼接3-氧化吲哚类化合物

以3-烯烃氧化吲哚为起始原料,甲苯为溶剂,与丙二腈或腈基乙酸乙酯发生区域选择性Michael/Aldol串联反应,合成了6个新型的1′-茚醇拼接3-氧化吲哚类化合物,收率73%~90%, dr高达10/1,其结构经¹H NMR, ¹³C NMR和HR-MS（ESI-TOF）表征。     

有机催化的不对称N-磺酰基-1-氮杂-1，3-丁二烯与醛的反电子需求的氮杂Diels-Alder反应

光学纯的哌啶衍生物是构建天然产物与药物的一类重要中间体．立体选择性的氮杂Diels-Alder反应（ADAR）是有机合成中构建手性哌啶类衍生物最为高效的方法之一．     

Synthesis and Antitumor Activity of a New 7-Azaindole Derivative

We designed and synthesized a 7-azaindole derivative（TH1082）, which was characterized by 1^H NMR and 13^C-NMR. We investigated its antitumor effects on human melanoma A375 cells, human liver cancer SMMC cells and human breast cancer MCF-7 cells in vitro via 3-（4,5-dimethyldiazol-2-yl）-2,5-diphenyl-tetrazolium bromide （MTT） assay and also explored the mechanism of antiproliferation of them. The results show that TH1082 significantly inhibited the proliferation of these cells to different extent. The IC50 values for A375 cells, SMMC cells and MCF-7 cells were 25.38, 48.70 and 76.94 μg/mL at 24 h, respectively. To observe cell morphological changes, acridine orange/ethidium bromide（AO/EB） staining and Hoechest33342/Pl staining were carried out. These results indicate that TH1082 could induced the apoptosis of A375 cells. The apoptotic rates were （9.5±2.09）%, （18.9±2.25）% and （39.5±2.02）%（5, 10 and 20 μg/mL） for A375, SMMC and MCF-7 cell lines, respectively. Further, we determined the activities of caspase-3 and caspase-9 in A375 cells treated with TH1082 at different concentrations（0, 5, 10 and 20 μg/mL） or Z-VAD-FMK（20 μmol/L）, a pan-caspase inhibitor for 24 h. The results show that TH1082 activated caspase-3 and caspase-9, and the activation could be blocked by Z-VAD-FMK. Taken together, these findings indicate that TH 1082 could inhibit the proliferation ofA375 cells via activating caspase-3 and caspase-9.     

7—氮吲哚二体激发态双质子转移的量子化学研究

用AMl和INDO/CI方法研究了7-氮吲哚二体激发态双质子转移反应的位能面和机理,异构二体虽存在较强的分子内氢键,但基态时正常二体的能量仍比异构二体低,光照时正常二体可通过激发态质子转移变为异构二体,这是其荧光产生反常Stokes位移的原因。     

Catalytic,Regioselective 1,4-Fluorodifunctionalization of Dienes

A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp³)−F and C(sp³)−CF₃ groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.     

Catalytic,Regioselective 1,4-Fluorodifunctionalization of Dienes

A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp³)−F and C(sp³)−CF₃ groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.     

Carbolithiation of vinyl pyridines as a route to 7-azaindoles

An effective synthesis of the 7-azaindole ring system has been developed from substituted 2-amino-3-vinyl pyridines. The methodology involves a novel cascade reaction sequence of controlled carbolithiation of the vinyl double bond, subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by ring closure and dehydration.     

An Efficient Synthesis of Sulfonylhydrazides and Sulfonylsemicarbazides by Utilizing Alumina as a Catalyst

Sulfonyl hydrazides and sulfonyl semicarbazides are readily prepared by the reacting of hydrazine derivatives with sulfonyl chlorides in the presence of basic alumina under solvent‐free conditions. Reaction of a sulfonyl chloride with t‐butylcarbazate, followed by hydrolysis provides the corresponding sulfonyl hydrazides in higher yield and shorter time than previously reported.     

7-Azaindoles via carbolithiation of vinyl pyridines

The sequential reactions of a pyridine vinylation and alkene carbolithiation constitutes a new route to substituted 7-azaindoles. The methodology involves a reaction sequence of controlled carbolithiation of the vinyl double bond, subsequent trapping of the formal di-anion intermediate with a suitable electrophile, followed by an in situ ring closure and dehydration. The reaction sequence allows for aryl, heteroaryl, alkyl and keto substituents to be included at different positions around the heterocycle.     

A catalyst-and solvent-free multicomponent synthesis of 7-azagramine analogues via a Mannich type reaction

A catalyst-and solvent-free protocol for the synthesis of 7-azagramine analogues is described via a three-component Mannich type reaction between 7-azaindole, aromatic aldehydes and heterocyclic amines in acceptable to excellent yields. Structures of the compounds were confirmed satisfactorily by ¹H NMR, IR, mass, TOCSY, HSQC and HMBC spectral analyses.     

Synthesis of functionalized 7-azaindoles via directed ortho-metalations

Functionalization at C-5 of 4-fluoro- and 4-chloro-1-triisopropylsilyl-7-azaindole, 1 and 2, respectively, leads to a variety of new substituted 7-azaindole derivatives. We also describe two approaches to introduce functionality at C-6.     

New very mild conditions for the opening of an epoxide assisted by a neighboring carbonyl group

An epoxide is opened stereo- and regio-selectively by 1,3-endo migration of a phenylthiogroup in almost neutral conditions. The thioether is then reduced to give the alcohol corresponding to the starting epoxide in an excellent yield.