WO2023137771A1 - METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND - Google Patents

METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND Download PDF

Info

Publication number
WO2023137771A1
WO2023137771A1 PCT/CN2022/073602 CN2022073602W WO2023137771A1 WO 2023137771 A1 WO2023137771 A1 WO 2023137771A1 CN 2022073602 W CN2022073602 W CN 2022073602W WO 2023137771 A1 WO2023137771 A1 WO 2023137771A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl substituted
indole
synthesizing
reaction
substituted indole
Prior art date
Application number
PCT/CN2022/073602
Other languages
French (fr)
Chinese (zh)
Inventor
孙宏枚
孟蝶蝶
Original Assignee
苏州大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 苏州大学 filed Critical 苏州大学
Priority to PCT/CN2022/073602 priority Critical patent/WO2023137771A1/en
Publication of WO2023137771A1 publication Critical patent/WO2023137771A1/en

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms

Abstract

Provided is a novel method for synthesizing an α-alkyl substituted indole-3-carboxaldehyde compound, that is, in the presence of magnesium chips, an iron (III) complex containing a 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation is used as a catalyst, and the α-alkyl substituted indole-3-carboxaldehyde compound is synthesized by means of a hydroheteroarylation reaction between an arylethene and an indole-3-carboxaldehyde imine. Compared with existing synthesis techniques, the method avoids the use of a sensitive and flammable Grignard reagent and an additive TMEDA, and thus is safer and more atom-economical, meanwhile, the applicability of a substrate is also greater, and this is the first case of a hydroheteroarylation reaction realized by an iron-based catalyst under the action of magnesium chips.

Description

一种合成α-烷基取代吲哚-3-甲醛类化合物的方法A method for synthesizing α-alkyl substituted indole-3-carboxaldehyde compounds 技术领域technical field
本发明属于有机合成制备技术领域，具体涉及到一种合成α-烷基取代吲哚-3-甲醛类化合物的新方法。The invention belongs to the technical field of organic synthesis preparation, and specifically relates to a new method for synthesizing α-alkyl substituted indole-3-carbaldehyde compounds.
背景技术Background technique
α-烷基取代吲哚-3-甲醛是一类重要的结构片段，广泛存在于天然产物、药物和生物活性分子中，具有重要的合成价值。在过去的十多年间，过渡金属催化的芳基乙烯与吲哚类化合物的氢杂芳基化反应因其100%的原子经济性逐步发展成为一种合成α-烷基取代吲哚类化合物的新方法。但是，目前涉及铁系催化剂的文献报道只有两篇。2015年，Yoshikai课题组在敏感易燃的格氏试剂环己基氯化镁（CyMgCl）和过量的添加剂N,N,N',N'-四甲基乙二胺（TMEDA）存在下，以乙酰丙酮铁（Fe(acca) 3）和咪唑盐SIXyl∙HCl（SIXyl为1，3-二（2, 6-二甲基苯基）咪唑啉阳离子）为催化体系，实现了芳基乙烯与吲哚-3-甲醛亚胺的氢杂芳基化反应。2017年，Ackermann课题组在敏感易燃的格氏试剂CyMgCl和过量的添加剂TMEDA存在下，以Fe(acca) 3和手性咪唑盐为催化体系，实现了芳基乙烯与吲哚-3-甲醛亚胺的对映选择性氢杂芳基化反应。由此可见，目前报道的铁系催化剂催化的芳基乙烯与吲哚类化合物的氢杂芳基化反应都需要使用敏感易燃的格氏试剂和过量的添加剂TMEDA才能使反应得以进行，这既限制了其官能团耐受性（例如对三氟甲基苯乙烯、对三甲基硅基苯乙烯、对吗啉苯乙烯、2-乙烯基吡啶和2-乙烯基苯并呋喃等其不能耐受），同时也降低了反应的原子经济性。因此，需要研发新的制备方法以提高合成α-烷基取代吲哚-3-甲醛类化合物的安全性以及工业实用性。 α-Alkyl-substituted indole-3-carbaldehydes are an important class of structural fragments, which widely exist in natural products, drugs and bioactive molecules, and have important synthetic value. In the past ten years, the transition metal-catalyzed hydroheteroarylation of arylethenes with indoles has gradually developed into a new method for the synthesis of α-alkyl substituted indoles due to its 100% atom economy. However, there are only two literature reports involving iron-based catalysts. In 2015, Yoshikai’s research group used iron acetylacetonate (Fe(acca) 3 ) and imidazolium salt SIXyl∙HCl (SIXyl is 1,3-bis(2,6-dimethylphenyl)imidazolinium cation) in the presence of sensitive and flammable Grignard reagent cyclohexylmagnesium chloride (CyMgCl) and excess additive N,N,N',N'-tetramethylethylenediamine (TMEDA) to realize arylethene Hydroheteroarylation reaction with indole-3-carboxylimine. In 2017, Ackermann's research group realized the enantioselective hydroheteroarylation reaction of arylethenes with indole-3-formaldehyde imine in the presence of sensitive and flammable Grignard reagent CyMgCl and excess additive TMEDA, using Fe(acca) 3 and chiral imidazolium salt as the catalytic system. It can be seen that the hydrogen heteroarylation reactions of arylethenes and indoles catalyzed by iron-based catalysts currently reported require the use of sensitive and flammable Grignard reagents and excess additive TMEDA to enable the reaction to proceed, which not only limits their functional group tolerance (such as trifluoromethylstyrene, p-trimethylsilylstyrene, p-morpholine styrene, 2-vinylpyridine and 2-vinylbenzofuran, etc.), but also reduces the atom economy of the reaction. Therefore, it is necessary to develop a new preparation method to improve the safety and industrial applicability of synthesizing α-alkyl substituted indole-3-carbaldehyde compounds.
技术问题technical problem
本发明的目的是提供一种合成α-烷基取代吲哚-3-甲醛类化合物的新方法，在镁屑存在下，以含1，3-二（2，4，6-三甲基苯基）咪唑阳离子的铁(III)配合物为催化剂，通过芳基乙烯与吲哚-3-甲醛亚胺的氢杂芳基化反应合成α-烷基取代吲哚-3-甲醛类化合物，本发明无需现有技术必要的格氏试剂以及TMEDA，而且催化剂是一种简单易得、具有明确结构和空气稳定性的铁(III)配合物。The object of the present invention is to provide a new method for the synthesis of α-alkyl substituted indole-3-carbaldehyde compounds. In the presence of magnesium chips, iron (III) complexes containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cations are used as catalysts to synthesize α-alkyl substituted indole-3-carbaldehyde compounds through the hydroheteroarylation reaction of arylethenes and indole-3-formaldehyde imines. Iron(III) complexes with well-defined structures and air stability.
技术解决方案technical solution
本发明采用如下技术方案：一种合成α-烷基取代吲哚-3-甲醛类化合物的方法，包括以下步骤，在惰性气体气氛中，催化剂、镁、吲哚-3-甲醛亚胺、芳基乙烯和溶剂，然后进行反应，再经过酸化，得到α-烷基取代吲哚-3-甲醛类化合物；具体的，反应后用稀盐酸酸化，然后用乙酸乙酯萃取，通过柱层析分离提纯，得到α-烷基取代吲哚-3-甲醛类化合物，可进行定量分析。催化剂为含1，3-二（2，4，6-三甲基苯基）咪唑阳离子的铁(III)配合物。The present invention adopts the following technical scheme: a method for synthesizing α-alkyl substituted indole-3-carbaldehyde compounds, comprising the following steps: in an inert gas atmosphere, catalyst, magnesium, indole-3-formaldehyde imine, aryl vinyl and a solvent are reacted, and then acidified to obtain α-alkyl substituted indole-3-carbaldehyde compounds; specifically, acidified with dilute hydrochloric acid after the reaction, then extracted with ethyl acetate, separated and purified by column chromatography to obtain α-alkyl substituted indole-3-carbaldehyde compounds , for quantitative analysis. The catalyst is an iron (III) complex containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation.
含1，3-二（2，4，6-三甲基苯基）咪唑阳离子的铁(III)配合物在合成α-烷基取代吲哚-3-甲醛类化合物反应中的应用。Application of iron (III) complex containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation in the synthesis of α-alkyl substituted indole-3-carbaldehyde compounds.
本发明中，含1，3-二（2，4，6-三甲基苯基）咪唑阳离子的铁(III)配合物为[HIMes][FeBr 4]，其化学结构式如下： 。 In the present invention, the iron (III) complex containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation is [HIMes][FeBr 4 ], and its chemical structural formula is as follows: .
本发明中，吲哚-3-甲醛亚胺由下列化学结构式表达： 。 In the present invention, indole-3-formaldimine is expressed by the following chemical structural formula: .
R 1为氢、甲基、甲氧基、氟中的一种；R 2为甲基或者苄基。 R 1 is one of hydrogen, methyl, methoxy and fluorine; R 2 is methyl or benzyl.
本发明中，芳基乙烯由下列化学结构式表达： 。 In the present invention, arylethene is expressed by the following chemical structural formula: .
Ar为芳基、取代芳基、杂环芳基；优选的，芳基乙烯包括苯乙烯、邻甲氧基苯乙烯、间甲氧基苯乙烯、对甲氧基苯乙烯、对甲基苯乙烯、对三氟甲基苯乙烯、对三甲基硅基苯乙烯、对二苯胺基苯乙烯、对吗啉苯乙烯、2-乙烯基萘、2-乙烯基吡啶或者2-乙烯基苯并呋喃。Ar is an aryl group, a substituted aryl group, or a heterocyclic aryl group; preferably, aryl vinyl includes styrene, o-methoxystyrene, m-methoxystyrene, p-methoxystyrene, p-methylstyrene, p-trifluoromethylstyrene, p-trimethylsilylstyrene, p-dianilinostyrene, p-morpholine styrene, 2-vinylnaphthalene, 2-vinylpyridine or 2-vinylbenzofuran.
本发明中，α-烷基取代吲哚-3-甲醛类化合物由下列化学结构式表达： 。 In the present invention, the α-alkyl substituted indole-3-carboxaldehyde compound is expressed by the following chemical structural formula: .
式中取代基源自吲哚-3-甲醛亚胺、芳基乙烯。In the formula, the substituents are derived from indole-3-formaldehyde imine and arylethene.
上述技术方案中，所述反应的温度为25～80 ℃，时间为16～48小时。In the above technical solution, the temperature of the reaction is 25-80° C., and the time is 16-48 hours.
上述技术方案中，所述惰性气体为氩气或者氮气；所述溶剂为四氢呋喃、2-甲基四氢呋喃等。In the above technical solution, the inert gas is argon or nitrogen; the solvent is tetrahydrofuran, 2-methyltetrahydrofuran and the like.
上述技术方案中，催化剂、镁、吲哚-3-甲醛亚胺、芳基乙烯的摩尔比为0.03～0.08∶0.8～1∶1∶1.2～1.6。优选的技术方案中，以物质的量计，芳基乙烯的用量是吲哚类化合物的1.5倍，镁的用量是吲哚类化合物的1倍，催化剂的用量是吲哚类化合物摩尔量的5 %；反应的温度是40℃，反应的时间为24小时。In the above technical solution, the molar ratio of catalyst, magnesium, indole-3-formaldimine and aryl vinyl is 0.03-0.08:0.8-1:1:1.2-1.6. In the preferred technical scheme, in terms of the amount of substances, the amount of arylethene is 1.5 times that of indole compounds, the amount of magnesium is 1 time that of indole compounds, and the amount of catalyst is 5% of the molar weight of indole compounds; the reaction temperature is 40 ° C, and the reaction time is 24 hours.
本发明制备α-烷基取代吲哚-3-甲醛类化合物的反应过程可如下表示： 。 The present invention prepares the reaction process of α-alkyl substituted indole-3-carboxaldehyde compound and can be represented as follows: .
有益效果Beneficial effect
由于上述技术方案的运用，本发明具有下列优点：1.  本发明在镁屑存在下，以含1，3-二（2，4，6-三甲基苯基）咪唑阳离子的铁(III)配合物为催化剂，实现了芳基乙烯与吲哚-3-甲醛亚胺的氢杂芳基化反应，为合成α-烷基取代吲哚-3-甲醛类化合物提供了一种新方法。Due to the application of the above-mentioned technical scheme, the present invention has the following advantages: 1. The present invention, in the presence of magnesium chips, uses iron (III) complexes containing 1,3-two (2,4,6-trimethylphenyl) imidazolium cations as catalysts to realize the hydroheteroarylation reaction of arylethenes and indole-3-formaldehyde imines, and provides a new method for the synthesis of α-alkyl substituted indole-3-formaldehyde compounds.
2.  本发明公开的制备方法条件温和，不需要使用敏感易燃的格氏试剂和过量的添加剂，具有较好的底物适用性，不仅适用于含供电子取代基的芳基乙烯，也适用于含吸电子取代基的芳基乙烯以及杂环烯烃。2. The preparation method disclosed in the present invention has mild conditions, does not need to use sensitive and flammable Grignard reagents and excessive additives, and has good substrate applicability. It is not only suitable for arylethenes containing electron-donating substituents, but also for arylethenes and heterocyclic alkenes containing electron-withdrawing substituents.
本发明的实施方式Embodiments of the present invention
本发明的原料为市售产品，具体操作方法以及测试方法为本领域常规方法，收率为分离收率（表中除外）。The raw materials of the present invention are commercially available products, the specific operation method and test method are conventional methods in this field, and the yield is the separation yield (except in the table).
下面结合实施例对本发明作进一步描述：实施例一：含1,3-二（2,4,6-三甲基苯基）咪唑阳离子（分子式为[HIMes][FeBr 4]），（[HIMes]为1,3-二（2,4,6-三甲基苯基）咪唑阳离子）的铁(III)配合物的合成。 The following examples will further describe the present invention: Example 1: Synthesis of iron (III) complexes containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation (molecular formula is [HIMes][FeBr 4 ]), ([HIMes] is 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation).
将1,3-二（2,4,6-三甲基苯基）咪唑溴盐（0.38克，1.0毫摩尔）加入到三溴化铁（0.27克，0.9毫摩尔）的四氢呋喃溶液中，60 oC下反应24小时，真空抽去溶剂，己烷洗涤，抽干，用四氢呋喃萃取，离心清液转移，在清液中加入己烷重结晶，室温下析出红棕色固体粉末，产率85%。化学结构式如下： 。 Add 1,3-two (2,4,6-triozylene) imidazole bromodoline (0.38 grams, 1.0 mmol) into tetrahydride solution of trifle iron (0.27 grams, 0.9 mmore), reacts for 24 hours under 60 OC , vacuum removing solvent, hexane washing, drying with tetrahydrofuu, rotating centrifugal cleaner liquid clearing fluid, Move it, add hexane to the hendane to crystal, and the red -brown solid powder is analyzed at room temperature, with an yield of 85%. The chemical structural formula is as follows: .
对产物进行元素分析，结果如下所示：元素分析 。 Carry out elemental analysis to the product, the result is as follows: Elemental analysis .
由于铁的配合物有顺磁性，所以没有对其进行核磁表征。Since the iron complex is paramagnetic, it was not characterized by NMR.
配合物[HIMes][FeBr 4]是以离子对的形式存在的，其中阴离子[FeBr 4] -通过拉曼光谱进行了表征，发现其在204 cm -1处有特征峰，与文献报道的相符合（Melissa, S. S.; Eric, R. S.; Eric, V. P.; Freeman, R. G., Inorg. Chem., 2001, 40, 2298）。配合物的阳离子部分[HIMes] +通过质谱进行了表征，发现其在305.2011处有一个分子离子峰，理论上此分子离子峰在305.2012，实测与理论一致。证明所得化合物为目标化合物。 The complex [HIMes][FeBr 4 ] exists in the form of ion pairs, and the anion [FeBr 4 ] - is characterized by Raman spectroscopy, and it is found that it has a characteristic peak at 204 cm -1 , which is consistent with the reports in the literature (Melissa, SS; Eric, RS; Eric, VP; Freeman, RG, Inorg. Chem. , 2001 , 40 , 2298). The cationic part of the complex [HIMes] + was characterized by mass spectrometry, and it was found that it had a molecular ion peak at 305.2011, which was theoretically at 305.2012, and the measured and theoretical results were consistent. It was proved that the obtained compound was the target compound.
实施例二 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，再加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率93%。 Example 2 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and styrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol) successively in the reaction flask , tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified with dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 93%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.42 (d, J = 7.6 Hz, 1H), 7.31 – 7.21 (m, 10H), 7.14 (d, J = 8.1 Hz, 1H), 6.95 – 6.86 (m, 2H), 5.22 (s, 2H), 5.05 (q, J = 7.3, 6.8 Hz, 1H), 1.74 (d, J = 7.3 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.42 (d, J = 7.6 Hz, 1H), 7.31 – 7.21 (m, 10H), 7.14 (d, J = 8.1 Hz, 1H), 6.95 – 6.86 (m, 2H), 5.22 (s, 2H), 5.05 (q, J = 7.3, 6.8 Hz, 1H), 1.74 (d, J = 7.3 Hz, 3H).
在上述苯乙烯与 N-苄基吲哚-3-甲醛亚胺的反应的基础上做单因素变化，结果如下 。 On the basis of the reaction of above-mentioned styrene and N -benzyl indole-3-formaldehyde imine, do single factor change, the result is as follows .
a 反应条件： N-苄基吲哚-3-甲醛亚胺（0.5 mmol），苯乙烯（0.75 mmol），铁催化剂（5 mol%），添加剂（0.5 mmol），四氢呋喃（1.5 mL），24 h，产物的收率以正十二烷作为内标通过气相确定。 b 分离收率。 a Reaction conditions: N -benzyl indole-3-formaldimine (0.5 mmol), styrene (0.75 mmol), iron catalyst (5 mol%), additives (0.5 mmol), tetrahydrofuran (1.5 mL), 24 h, the yield of the product was determined by gas phase with n-dodecane as internal standard. bIsolation yield.
[HItBu][FeBr 4] 化学结构式如下： 。 The chemical structure of [HItBu][FeBr 4 ] is as follows: .
实施例三 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与邻甲氧基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、邻甲氧基苯乙烯（100微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于25 oC下反应48小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率96%。 Example 3 [HIMes][FeBr 4] as a catalyst to catalyze the hydrogen heteroarylation reaction of N-benzyl indole-3-formaldehyde imine and o-methoxystyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), o-methoxystyrene (100 microliters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 25 oThe reaction was carried out at C for 48 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 96%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.21 (s, 1H), 8.44 (d, J = 7.7 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 3.7 Hz, 2H), 7.24 (d, J = 4.6 Hz, 3H), 7.02 – 6.97 (m, 3H), 6.76 (d, J = 8.2 Hz, 1H), 5.48 (s, 2H), 4.93 (q, J = 7.4 Hz, 1H), 3.61 (s, 3H), 1.66 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.21 (s, 1H), 8.44 (d, J = 7.7 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 3.7 Hz, 2H), 7.24 (d, J = 4.6 Hz, 3H), 7.02 – 6.97 (m, 3H), 6.76 (d, J = 8.2 Hz, 1H), 5.48 (s, 2H), 4.93 (q, J = 7.4 Hz, 1H), 3.61 (s, 3H), 1.66 (d, J = 7.4 Hz, 3H).
实施例四[HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与间甲氧基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、间甲氧基苯乙烯（100微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于25 oC下反应48小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率92%。 Example 4 [HIMes][FeBr 4] as a catalyst to catalyze the hydrogen heteroarylation reaction of N-benzyl indole-3-formaldehyde imine and m-methoxystyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), m-methoxystyrene (100 microliters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 25 oThe reaction was carried out at C for 48 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 92%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.42 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.26 – 7.13 (m, 6H), 6.93 – 6.89 (m, 2H), 6.80 (d, J = 7.8 Hz, 1H), 6.77 – 6.72 (m, 2H), 5.24 (s, 2H), 5.02 (q, J = 7.4 Hz, 1H), 3.72 (s, 3H), 1.73 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.42 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.26 – 7.13 (m, 6H), 6.93 – 6.89 (m, 2H), 6.80 (d, J = 7.8 Hz, 1H), 6.77 – 6.72 (m, 2H), 5.24 (s, 2H), 5.02 (q, J = 7.4 Hz, 1H), 3.72 (s, 3H), 1.73 (d, J = 7.4 Hz, 3H).
实施例五 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对甲氧基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、对甲氧基苯乙烯（104微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率92%。 Example five [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-methoxystyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), p-methoxystyrene (104 microliters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 92%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.44 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.27 – 7.25 (m, 3H), 7.24 – 7.21 (m, 1H), 7.14 (dd, J = 12.3, 8.3 Hz, 3H), 6.94 – 6.90 (m, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.24 (s, 2H), 5.00 (q, J = 7.4 Hz, 1H), 3.77 (s, 3H), 1.72 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.44 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.27 – 7.25 (m, 3H), 7.24 – 7.21 (m, 1H), 7.14 (dd, J = 12.3, 8.3 Hz, 3H), 6.94 – 6.90 (m, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.24 (s, 2H), 5.00 (q, J = 7.4 Hz, 1H), 3.77 (s, 3H), 1.72 (d, J = 7.4 Hz, 3H).
实施例六 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对甲基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、对甲基苯乙烯（99微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应16小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率95%。 Example 6 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-methylstyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), p-methylstyrene (99 μl, 0.7 5 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 16 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 95%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.26 (s, 1H), 8.52 – 8.46 (m, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.27 (dt, J = 5.6, 2.6 Hz, 3H), 7.23 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 8.2 Hz, 1H), 7.12 (s, 4H), 6.97 – 6.92 (m, 2H), 5.26 (s, 2H), 5.03 (q, J = 7.4 Hz, 1H), 2.33 (s, 3H), 1.75 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.26 (s, 1H), 8.52 – 8.46 (m, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.27 (dt, J = 5.6, 2.6 Hz, 3H), 7.23 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 8.2 Hz, 1H), 7.12 (s, 4H), 6.97 – 6.92 (m, 2H), 5.26 (s, 2H), 5.03 (q, J = 7.4 Hz, 1H), 2.33 (s, 3H), 1.75 (d, J = 7.4 Hz, 3H).
实施例七 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对三氟甲基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、对三氟甲基苯乙烯（111微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率68%。 Example 7 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-trifluoromethylstyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), p-trifluoromethyl styrene (111 μm liters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 60 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using ethyl acetate/petroleum ether volume ratio of 1:5 mixed solvent as the developing solvent), and the yield was 68%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.2 Hz, 2H), 7.32 (t, J = 8.5 Hz, 3H), 7.27 – 7.23 (m, 4H), 7.20 (d, J = 8.2 Hz, 1H), 6.89 – 6.84 (m, 2H), 5.24 (s, 2H), 5.13 (d, J = 7.4 Hz, 1H), 1.79 (d, J = 7.3 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.23 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.2 Hz, 2H), 7.32 (t, J = 8.5 Hz, 3H), 7.27 – 7.23 (m, 4H), 7.20 (d, J = 8.2 Hz, 1H), 6.89 – 6.84 (m, 2H), 5.24 (s, 2H), 5.13 (d, J = 7.4 Hz, 1H), 1.79 (d, J = 7.3 Hz, 3H).
实施例八 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对三甲基硅基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、三甲基硅基苯乙烯（154微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率92%。 Example eight [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-trimethylsilylstyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), trimethylsilyl styrene (154 microliter, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 92%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.26 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 7.45 (d, J = 7.7 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.27 – 7.22 (m, 6H), 7.18 (d, J = 8.1 Hz, 1H), 6.95 – 6.91 (m, 2H), 5.29 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.78 (d, J = 7.4 Hz, 3H), 0.28 (s, 9H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.26 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 7.45 (d, J = 7.7 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.27 – 7.22 (m, 6H), 7.18 (d, J = 8.1 Hz, 1H), 6.95 – 6.91 (m, 2H), 5.29 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.78 (d, J = 7.4 Hz, 3H), 0.28 (s, 9H).
实施例九 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对二苯氨基苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、对二苯氨基苯乙烯（271.0毫克，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率93%。 Example 9 [HIMes][FeBr 4] as a catalyst to catalyze the hydrogen heteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-diphenylaminostyrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), p-diphenylaminostyrene (271. 0 mg, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oC for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using ethyl acetate/petroleum ether volume ratio of 1:5 mixed solvent as developing solvent), the yield was 93%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.46 (s, 1H), 8.63 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 7.7 Hz, 1H), 7.44 (dt, J = 5.9, 3.2 Hz, 4H), 7.39 (d, J = 7.3 Hz, 3H), 7.32 – 7.26 (m, 3H), 7.23 – 7.14 (m, 9H), 7.12 – 7.09 (m, 2H), 5.57 – 5.45 (m, 2H), 5.19 (q, J = 7.3 Hz, 1H), 1.93 (d, J = 7.3 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.46 (s, 1H), 8.63 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 7.7 Hz, 1H), 7.44 (dt, J = 5.9, 3.2 Hz, 4H), 7.39 (d, J = 7.3 Hz, 3H), 7.32 – 7.26 (m, 3H), 7.23 – 7.14 (m, 9H), 7.12 – 7.09 (m, 2H), 5.57 – 5.45 (m, 2H), 5.19 (q, J = 7.3 Hz, 1H), 1.93 (d, J = 7.3 Hz, 3H).
实施例十 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与对吗啉苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、对吗啉苯乙烯（142.0毫克，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率92%。 Example 10 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and p-morpholine styrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), p-morpholine styrene (142.0 mg , 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 92%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.24 (s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 7.34 – 7.25 (m, 4H), 7.22 (d, J = 7.2 Hz, 1H), 7.13 (dd, J = 15.1, 8.4 Hz, 3H), 6.92 (d, J = 5.0 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 5.25 (s, 2H), 4.98 (q, J = 7.3 Hz, 1H), 3.86 (s, 4H), 3.12 (s, 4H), 1.72 (d, J = 7.3 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.24 (s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 7.34 – 7.25 (m, 4H), 7.22 (d, J = 7.2 Hz, 1H), 7.13 (dd, J = 15.1, 8.4 Hz, 3H), 6.92 (d, J = 5.0 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 5.25 (s, 2H), 4.98 (q, J = 7.3 Hz, 1H), 3.86 (s, 4H), 3.12 (s, 4H), 1.72 (d, J = 7.3 Hz, 3H).
实施例十一 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与2-乙烯基萘的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、2-乙烯基萘（154毫克，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率88%。 Example 11 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and 2-vinylnaphthalene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), 2-vinylnaphthalene (154 mg, 0 .75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using ethyl acetate/petroleum ether volume ratio of 1:5 mixed solvent as developing solvent), the yield was 88%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.30 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 7.90 – 7.72 (m, 5H), 7.50 (dd, J = 6.7, 3.1 Hz, 2H), 7.36 (s, 1H), 7.28 – 7.23 (m, 4H), 7.19 (s, 1H), 6.92 (d, J = 7.8 Hz, 2H), 5.26 (d, J = 7.9 Hz, 3H), 1.89 (s, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.30 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 7.90 – 7.72 (m, 5H), 7.50 (dd, J = 6.7, 3.1 Hz, 2H), 7.36 (s, 1H), 7.28 – 7.23 (m, 4H), 7.19 (s, 1H), 6.92 (d, J = 7.8 Hz, 2H), 5.26 (d, J = 7.9 Hz, 3H), 1.89 (s, 3H).
实施例十二 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与2-乙烯基吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、2-乙烯基吡啶（81微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于50 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率72%。 Example 12 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and 2-vinylpyridine: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), 2-vinylpyridine (81 μl , 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 50 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using ethyl acetate/petroleum ether volume ratio of 1:5 mixed solvent as developing solvent), and the yield was 72%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.24 (s, 1H), 8.45 (d, J = 7.9 Hz, 1H), 7.33 – 7.26 (m, 3H), 7.25 – 7.19 (m, 6H), 7.14 (d, J = 8.2 Hz, 1H), 6.91 (dd, J = 6.9, 2.4 Hz, 2H), 5.23 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.24 (s, 1H), 8.45 (d, J = 7.9 Hz, 1H), 7.33 – 7.26 (m, 3H), 7.25 – 7.19 (m, 6H), 7.14 (d, J = 8.2 Hz, 1H), 6.91 (dd, J = 6.9, 2.4 Hz, 2H), 5.23 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H).
实施例十三 [HIMes][FeBr 4]为催化剂，催化N-苄基吲哚-3-甲醛亚胺与2-乙烯基苯并呋喃的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（33.8毫克，0.05毫摩尔，10 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基吲哚-3-甲醛亚胺（169.6毫克，0.5毫摩尔）、2-乙烯基苯并呋喃（102微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于50 oC下反应48小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率54%。 Example 13 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl indole-3-formaldehyde imine and 2-vinylbenzofuran: under the protection of argon, add catalyst (33.8 mg, 0.05 mmol, 10 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl indole-3-formaldehyde imine (169.6 mg, 0.5 mmol), 2-vinyl benzofuran ( 102 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 50 oThe reaction was carried out at C for 48 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 54%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3 δ 10.31 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 6.7 Hz, 1H), 7.31 (dt, J = 13.3, 6.4 Hz, 3H), 7.24 – 7.18 (m, 6H), 6.96 (d, J = 6.3 Hz, 2H), 6.57 (s, 1H), 5.44 (s, 2H), 5.13 (q, J = 7.1 Hz, 1H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3 δ 10.31 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 6.7 Hz, 1H), 7.31 (dt, J = 13.3, 6.4 Hz, 3H), 7.24 – 7.18 (m, 6H), 6.96 (d, J = 6.3 Hz, 2H), 6.57 (s, 1H), 5.44 (s, 2H), 5.13 (q, J = 7.1 Hz, 1H).
实施例十四 [HIMes][FeBr 4]为催化剂，催化N-甲基吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-甲基吲哚-3-甲醛亚胺（132.2毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率90%。 Example 14 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-methylindole-3-formaldehyde imine and styrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-methyl indole-3-formaldehyde imine (132.2 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), four Hydrofuran (1.5 ml) as solvent, at 40 oC for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 90%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.26 (s, 1H), 8.42 – 8.37 (m, 1H), 7.34 – 7.23 (m, 8H), 5.20 (q, J = 7.4 Hz, 1H), 3.44 (s, 3H), 1.87 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, and measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ) δ 10.26 (s, 1H), 8.42 – 8.37 (m, 1H), 7.34 – 7.23 (m, 8H), 5.20 (q, J = 7.4 Hz, 1H), 3.44 (s, 3H), 1.87 (d, J = 7.4 Hz, 3H).
实施例十五 [HIMes][FeBr 4]为催化剂，催化N-苄基-5-甲氧基吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-甲基-5-甲氧基吲哚-3-甲醛亚胺（185.1毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率91%。 Example 15 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl-5-methoxyindole-3-formaldehyde imine and styrene: under argon protection, catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-methyl-5-methoxyindole-3-formaldehyde imine (185.1 mg, 0.5 mmol), styrene (86 μg liters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 91%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.18 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.31 – 7.26 (m, 5H), 7.22 (d, J = 7.6 Hz, 3H), 7.04 (d, J = 8.9 Hz, 1H), 6.94 – 6.90 (m, 2H), 6.86 (dd, J = 8.9, 2.6 Hz, 1H), 5.21 (s, 2H), 4.98 (q, J = 7.4 Hz, 1H), 3.91 (s, 3H), 1.75 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.18 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.31 – 7.26 (m, 5H), 7.22 (d, J = 7.6 Hz, 3H), 7.04 (d, J = 8.9 Hz, 1H), 6.94 – 6.90 (m, 2H), 6.86 (dd, J = 8.9, 2.6 Hz, 1H), 5.21 (s, 2H), 4.98 (q, J = 7.4 Hz, 1H), 3.91 (s, 3H), 1.75 (d, J = 7.4 Hz, 3H).
实施例十六 [HIMes][FeBr 4]为催化剂，催化N-苄基-5-氟-吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-甲基-5-氟-吲哚-3-甲醛亚胺（179.1毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于40 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率87%。 Example 16 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl-5-fluoro-indole-3-formaldehyde imine and styrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-methyl-5-fluoro-indole-3-formaldehyde imine (179.1 mg, 0.5 mmol), styrene (86 μg liters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 40 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 ml), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using ethyl acetate/petroleum ether volume ratio of 1:5 mixed solvent as developing solvent), and the yield was 87%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.17 (s, 1H), 8.10 (dd, J = 9.4, 2.6 Hz, 1H), 7.28 (d, J = 7.5 Hz, 5H), 7.25 – 7.19 (m, 3H), 7.07 – 7.03 (m, 1H), 6.95 (td, J = 9.0, 2.6 Hz, 1H), 6.91 – 6.87 (m, 2H), 5.21 (d, J = 1.3 Hz, 2H), 5.00 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.17 (s, 1H), 8.10 (dd, J = 9.4, 2.6 Hz, 1H), 7.28 (d, J = 7.5 Hz, 5H), 7.25 – 7.19 (m, 3H), 7.07 – 7.03 (m, 1H), 6.95 (td, J = 9.0, 2.6 Hz, 1H), 6.91 – 6.87 (m, 2H), 5.21 (d, J = 1.3 Hz, 2H), 5.00 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H).
实施例十七 [HIMes][FeBr 4]为催化剂，催化N-苄基-6-氯-吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-甲基-6-氯-吲哚-3-甲醛亚胺（187.1毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于50 oC下反应24小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率80%。 Example 17 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl-6-chloro-indole-3-formaldehyde imine and styrene: under argon protection, catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-methyl-6-chloro-indole-3-formaldehyde imine (187.1 mg, 0.5 mmol), styrene (86 μg liters, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 50 oThe reaction was carried out at C for 24 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 80%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.18 (s, 1H), 8.34 (d, J = 8.4 Hz, 1H), 7.31 – 7.27 (m, 5H), 7.21 (dd, J = 16.9, 7.5 Hz, 4H), 7.14 (d, J = 1.7 Hz, 1H), 6.89 (dd, J = 7.2, 2.4 Hz, 2H), 5.20 – 5.17 (m, 2H), 4.98 (q, J = 7.4 Hz, 1H), 1.74 (d, J = 7.4 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.18 (s, 1H), 8.34 (d, J = 8.4 Hz, 1H), 7.31 – 7.27 (m, 5H), 7.21 (dd, J = 16.9, 7.5 Hz, 4H), 7.14 (d, J = 1.7 Hz, 1H), 6.89 (dd, J = 7.2, 2.4 Hz, 2H), 5.20 – 5.17 (m, 2H), 4.98 (q, J = 7.4 Hz, 1H), 1.74 (d, J = 7.4 Hz, 3H).
实施例十八 [HIMes][FeBr 4]为催化剂，催化N-苄基-7-甲基吲哚-3-甲醛亚胺与苯乙烯的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（16.9毫克，0.025毫摩尔，5 mol%）、镁屑（12.0毫克，0.5毫摩尔）、N-苄基-7-甲基吲哚-3-甲醛亚胺（177.1毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于80 oC下反应16小时，用水淬灭反应，加稀盐酸（2摩尔/升，1.5毫升）进行酸化，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以乙酸乙酯/石油醚体积比为1∶5的混合溶剂为展开剂），产率86%。 Example 18 [HIMes][FeBr 4] as a catalyst to catalyze the hydroheteroarylation reaction of N-benzyl-7-methylindole-3-formaldehydeimine and styrene: under the protection of argon, add catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium chips (12.0 mg, 0.5 mmol), N-benzyl-7-methylindole-3-formaldehyde imine (177.1 mg, 0.5 mmol), styrene (86 μl , 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, at 80 oThe reaction was carried out at C for 16 hours, quenched with water, acidified by adding dilute hydrochloric acid (2 mol/L, 1.5 mL), and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 86%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3) δ 10.21 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 7.31 – 7.26 (m, 5H), 7.20 (t, J = 7.6 Hz, 4H), 6.98 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 6.1 Hz, 2H), 5.48 (d, J = 5.7 Hz, 2H), 4 .97 (q, J = 7.4 Hz, 1H), 2.44 (s, 3H), 1.69 (d, J = 7.3 Hz, 3H)。 Dissolve the product in CDCl 3Medium (about 0.4 mL), seal the tube, measure and characterize on a Unity Inova-400 NMR instrument at room temperature: 1H NMR (400 MHz, CDCl 3) δ 10.21 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 7.31 – 7.26 (m, 5H), 7.20 (t, J = 7.6 Hz, 4H), 6.98 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 6.1 Hz, 2H), 5.48 (d, J = 5.7 Hz, 2H), 4 .97 (q, J = 7.4 Hz, 1H), 2.44 (s, 3H), 1.69 (d, J = 7.3 Hz, 3H).
现有技术对于铁系催化剂催化的芳基乙烯与吲哚-3-甲醛亚胺的氢杂芳基化反应都需要使用敏感易燃的格氏试剂和过量的添加剂TMEDA才能使反应得以进行，这就限制了其官能团耐受性和潜在应用价值。因此，本发明在镁屑存在下，以铁(III)配合物为催化剂，在温和的条件下通过芳基乙烯与吲哚-3-甲醛亚胺的氢杂芳基化反应来构建α-烷基取代吲哚-3-甲醛类化合物具有显而易见的创新性、安全性和更好的潜在应用价值。In the prior art, the hydroheteroarylation of arylethenes and indole-3-formaldimines catalyzed by iron-based catalysts requires the use of sensitive and flammable Grignard reagents and an excessive amount of additive TMEDA to enable the reaction to proceed, which limits its functional group tolerance and potential application value. Therefore, in the presence of magnesium chips, the present invention uses iron (III) complexes as catalysts to construct α-alkyl substituted indole-3-carboxaldehyde compounds through the hydroheteroarylation reaction of arylethenes and indole-3-carboxaldehyde imines under mild conditions, which has obvious innovation, safety and better potential application value.

Claims (10)

  1. 一种合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，包括以下步骤，在惰性气体气氛中，混合催化剂、镁、吲哚-3-甲醛亚胺、芳基乙烯和溶剂，然后进行反应，再经过酸化，得到α-烷基取代吲哚-3-甲醛类化合物；所述催化剂为含咪唑阳离子的铁(III)配合物。A method for synthesizing α-alkyl substituted indole-3-carbaldehyde compounds, characterized in that it comprises the following steps of mixing catalyst, magnesium, indole-3-formaldehyde imine, aryl vinyl and a solvent in an inert gas atmosphere, then reacting, and then acidifying to obtain α-alkyl substituted indole-3-carbaldehyde compounds; the catalyst is an iron (III) complex containing imidazolium cations.
  2. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，用盐酸酸化。The method for synthesizing α-alkyl substituted indole-3-carboxaldehydes according to claim 1, characterized in that the method is acidified with hydrochloric acid.
  3. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，所述催化剂为[HIMes][FeBr 4]。 The method for synthesizing α-alkyl substituted indole-3-carboxaldehyde compounds according to claim 1, characterized in that the catalyst is [HIMes][FeBr 4 ].
  4. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，吲哚-3-甲醛亚胺由下列化学结构式表达：The method for synthesizing α-alkyl substituted indole-3-formaldehyde compounds according to claim 1, is characterized in that, indole-3-formaldehyde imine is expressed by the following chemical structural formula:
    R 1为氢、甲基、甲氧基、氟中的一种；R 2为甲基或者苄基； R 1 is one of hydrogen, methyl, methoxy, fluorine; R 2 is methyl or benzyl;
    芳基乙烯由下列化学结构式表达：Arylvinyls are represented by the following chemical structural formula:
    Ar为芳基、取代芳基、杂环芳基。Ar is an aryl group, a substituted aryl group, or a heterocyclic aryl group.
  5. 根据权利要求4所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，芳基乙烯包括苯乙烯、邻甲氧基苯乙烯、间甲氧基苯乙烯、对甲氧基苯乙烯、对甲基苯乙烯、对三氟甲基苯乙烯、对三甲基硅基苯乙烯、对二苯胺基苯乙烯、对吗啉苯乙烯、2-乙烯基萘、2-乙烯基吡啶或者2-乙烯基苯并呋喃。According to the method for synthesizing α-alkyl substituted indole-3-carboxaldehydes according to claim 4, it is characterized in that aryl vinyl comprises styrene, o-methoxystyrene, m-methoxystyrene, p-methoxystyrene, p-methylstyrene, p-trifluoromethylstyrene, p-trimethylsilylstyrene, p-dianilinostyrene, p-morpholine styrene, 2-vinylnaphthalene, 2-vinylpyridine or 2-vinylbenzofuran.
  6. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，所述反应的温度为25～80 ℃，时间为16～48小时。The method for synthesizing α-alkyl substituted indole-3-carboxaldehyde compounds according to claim 1, characterized in that the temperature of the reaction is 25-80° C., and the time is 16-48 hours.
  7. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法，其特征在于，催化剂、镁、吲哚-3-甲醛亚胺、芳基乙烯的摩尔比为0.03～0.08∶0.8～1∶1∶1.2～1.6。The method for synthesizing α-alkyl substituted indole-3-formaldehyde compounds according to claim 1, characterized in that the molar ratio of catalyst, magnesium, indole-3-formaldehyde imine, and arylethene is 0.03～0.08:0.8～1:1:1.2～1.6.
  8. 根据权利要求1所述合成α-烷基取代吲哚-3-甲醛类化合物的方法制备的α-烷基取代吲哚-3-甲醛类化合物。The α-alkyl substituted indole-3-carbaldehyde compounds prepared by the method for synthesizing α-alkyl substituted indole-3-carbaldehyde compounds according to claim 1.
  9. 含咪唑阳离子的铁(III)配合物在合成α-烷基取代吲哚-3-甲醛类化合物反应中的应用，其特征在于，含咪唑阳离子的铁(III)配合物为[HIMes][FeBr 4]。 The application of the iron (III) complex containing imidazolium cation in the reaction of synthesizing α-alkyl substituted indole-3-formaldehyde compounds is characterized in that the iron (III) complex containing imidazolium cation is [HIMes][FeBr 4 ].
  10. 根据权利要求9所述的应用，其特征在于，反应在镁存在下进行。Use according to claim 9, characterized in that the reaction is carried out in the presence of magnesium.
PCT/CN2022/073602 2022-01-24 2022-01-24 METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND WO2023137771A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/073602 WO2023137771A1 (en) 2022-01-24 2022-01-24 METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/073602 WO2023137771A1 (en) 2022-01-24 2022-01-24 METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND

Publications (1)

Publication Number Publication Date
WO2023137771A1 true WO2023137771A1 (en) 2023-07-27

Family

ID=87347552

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/073602 WO2023137771A1 (en) 2022-01-24 2022-01-24 METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND

Country Status (1)

Country Link
WO (1) WO2023137771A1 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110330535A (en) * 2019-07-28 2019-10-15 苏州大学 N-heterocyclic carbine base mixed matching nickel (II) complex and its application
CN114478351A (en) * 2022-01-21 2022-05-13 苏州大学 Method for synthesizing alpha-alkyl substituted indole-3-formaldehyde compound

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110330535A (en) * 2019-07-28 2019-10-15 苏州大学 N-heterocyclic carbine base mixed matching nickel (II) complex and its application
CN114478351A (en) * 2022-01-21 2022-05-13 苏州大学 Method for synthesizing alpha-alkyl substituted indole-3-formaldehyde compound

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JOACHIM LOUP; DANIEL ZELL; JOÃO C. A. OLIVEIRA; HELENA KEIL; DIETMAR STALKE; LUTZ ACKERMANN: "Asymmetric Iron‐Catalyzed C−H Alkylation Enabled by Remote Ligand meta‐Substitution", ANGEWANDTE CHEMIE, vol. 129, no. 45, 6 October 2017 (2017-10-06), DE , pages 14385 - 14389, XP071372840, ISSN: 0044-8249, DOI: 10.1002/ange.201709075 *
WENGANG XU; JIE HUI PEK; NAOHIKO YOSHIKAI: "Cobalt‐Catalyzed, Imine‐Directed Olefin Hydroarylation under Grignard‐Free Conditions", ADVANCES SYNTHESIS AND CATALYSIS, vol. 358, no. 15, 1 August 2016 (2016-08-01), Hoboken, USA, pages 2564 - 2568, XP072351115, ISSN: 1615-4150, DOI: 10.1002/adsc.201600403 *
WONG MUN YEE, YAMAKAWA TAKESHI, YOSHIKAI NAOHIKO: "Iron-Catalyzed Directed C2-Alkylation and Alkenylation of Indole with Vinylarenes and Alkynes", ORGANIC LETTERS, vol. 17, no. 3, 6 February 2015 (2015-02-06), US , pages 442 - 445, XP093079754, ISSN: 1523-7060, DOI: 10.1021/ol503395g *

Similar Documents

Publication Publication Date Title
WO2021212734A1 (en) Application of mixed n-heterocyclic carbene-based nickel (ii) complex in reaction for synthesizing 2-linear alkylbenzothiazole compound
CN111763135A (en) Application of deprotonated phenyl bridged beta-ketimine lithium compound in preparation of alcohol from ester
CN114478351B (en) Method for synthesizing alpha-alkyl substituted indole-3-formaldehyde compound
Thwaite et al. The auration of 2-hydroxy-pyridine (2-pyridone): preparative and structural studies and a comparison with reactions of related aliphatic O, N-donors
WO2023137771A1 (en) METHOD FOR SYNTHESIZING α-ALKYL SUBSTITUTED INDOLE-3-CARBOXALDEHYDE COMPOUND
CN107915653B (en) Method for preparing amide by catalyzing ester and amine to react
CN111484441A (en) Indole triarylmethane derivative and synthetic method thereof
CN111217847A (en) Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction
WO2022155936A1 (en) Method for synthesizing aryl benzyl ether compound
JP3957346B2 (en) Method for producing optically active alcohol
CN111484440B (en) Indole triarylmethane derivative based on phenylboronic acid and synthetic method thereof
CN114539305B (en) Method for preparing double bond organic compound by dearomatization of benzofuran
Green et al. Synthesis, characterisation, and reactivity of (η 6-indene)(η-indenyl) rhenium: a precursor to hetero-bimetallic (µ-η 3: η 6-indenyl) derivatives
Yu-hua et al. Synthesis and reactions of chiral clusters containing an SRuCoMo core
CN111484439B (en) Indole triarylmethane derivative based on salicylaldehyde and synthetic method thereof
CN112110800B (en) 3-aryl-2-propyne-1-alcohol derivative and preparation method thereof
CN112574092B (en) Green novel method for preparing 2-diaryl methyl substituted indole compound
CN114632551B (en) Difunctional chiral catalyst and preparation method and application thereof
CN113061121B (en) Method for catalyzing hydrodesulfurization of thioamide derivative
CN111484397B (en) (2-hydroxyphenyl) (2,4, 6-trimethoxyphenyl) (phenyl) methane and synthesis method thereof
CN109081785B (en) Synthetic method of fluorine-containing glycine ester derivative
Du et al. Monocarbollide complexes of molybdenum and tungsten: functionalization through reactions at a cage boron centre
CN117510392A (en) Preparation method of bisindolyl compound
CN117126077A (en) Method for synthesizing 4-aryl nitrile compound
CN113087748A (en) Tetra (4-formylphenyl) ferrocene, and preparation method and application thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22921207

Country of ref document: EP

Kind code of ref document: A1