WO2015024403A1 - 一种氮杂卡宾类钯催化剂及其制备方法和应用 - Google Patents

一种氮杂卡宾类钯催化剂及其制备方法和应用 Download PDF

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WO2015024403A1
WO2015024403A1 PCT/CN2014/078652 CN2014078652W WO2015024403A1 WO 2015024403 A1 WO2015024403 A1 WO 2015024403A1 CN 2014078652 W CN2014078652 W CN 2014078652W WO 2015024403 A1 WO2015024403 A1 WO 2015024403A1
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group
formula
azacarbene
palladium catalyst
reaction
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PCT/CN2014/078652
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French (fr)
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沈安
曹育才
吴向阳
叶晓峰
倪晨
李永清
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上海化工研究院
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Priority to US14/910,456 priority Critical patent/US9656256B2/en
Priority to DE112014002844.4T priority patent/DE112014002844B4/de
Publication of WO2015024403A1 publication Critical patent/WO2015024403A1/zh

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Definitions

  • the invention relates to a novel structure of palladium catalyst and preparation and use thereof, in particular to a novel structure, multifunctional, high activity nitrogen carbene (NHC) type palladium catalyst and preparation thereof, and the use thereof in various coupling reactions .
  • NEC nitrogen carbene
  • the transition metal catalyzed C-C bond coupling reaction is a very effective means of organic synthesis by which the formation of C-C bonds at specific positions can be achieved under relatively mild conditions. Therefore, it can be used in the synthesis of a variety of natural products, pharmaceutical intermediates, and organic materials, both in academic research and industrial development.
  • the cross-coupling reaction catalyzed by transition metal palladium is particularly rapid [Org. Process Res. Dev. 2005, 9, 253).
  • organometallic palladium catalysts have been continuously developed to revolutionize the transition metal-catalyzed C-C bond coupling reaction.
  • halogenated aromatic hydrocarbons halogenated aromatic hydrocarbons, alkenyl halides and the like can be well coupled to various olefins, alkynes, aromatic compounds or organometallic reagents.
  • Extensive functional group tolerance and mild reaction conditions demonstrate good industrial potential. But how to reduce the amount of catalyst is a crucial issue.
  • the yield of the reaction can reach 90% or more at a dosage of 500 ppm of the catalyst.
  • the effect is very general (: ⁇ Patent 1, 199, 292, 2001).
  • Hartwig et al. reported a ligand based on ferrocene structure, which can be used to catalyze the Buchwald-Hartwig reaction of iodoaromatics, brominated aromatics and even chlorinated aromatic hydrocarbons with palladium acetate using only 50-2000 ppm of catalyst.
  • the reaction yield can reach more than 90% (Am. Chem. Soc. 2008, 130, 6586).
  • the object of the present invention is to provide a novel structure, multifunctional, highly reactive azacarbene (NHC)-based palladium catalyst, and a preparation method and application thereof, in particular, capable of over 500 ppm, in order to overcome the defects of the prior art described above.
  • the catalytic cross-coupling reaction of Suzuki-Miyaura, Heck, Buchwald-Hartwig, Kumada-Tamao-Corriu Sonogashira, Negishi, and ⁇ -oxime arylation reaction is catalyzed by the amount.
  • the aza-carbene-based palladium catalyst has the following molecular structure:
  • RR 2 , R 3 , R 4 and R 5 each independently represent 11, a fluorenyl group, a heterofluorenyl group or an aryl group
  • R 6 , R 7 and R 8 each independently represent H, a fluorenyl group and a hydrazine group
  • R 9 represents a fluorenyl group or an arylalkenyl group
  • R 1Q and R 11 each independently represent H, a fluorenyl group, a heterofluorenyl group or an aryl group
  • Y represents C1 or OAc.
  • Said RR 3 and R 5 independently represent H, dC 15 straight or branched fluorenyl, C r C 15 nitrogen or oxa straight or branched fluorenyl, aromatic hydrocarbon, preferably H, d-do Linear or branched fluorenyl and d-do nitrogen or oxa straight or branched fluorenyl;
  • the linear or branched fluorenyl group of the Crdo and the d-do nitrogen- or oxa-containing linear or branched fluorenyl group include H, methyl, ethyl, isopropyl, isobutyl, 1-ethyl Propyl, 1-phenylpropyl, cyclohexyl, nitrodimethyl, nitrogen diethyl, methoxy, ethoxy.
  • R 6 represents a substituent at a different position on the benzene ring, and comprises H, F, 2-methyl, 4-methyl, 3,5-dimethyl, 2-methoxy, 4-methoxy, 3,5-dimethoxy, 4-tert-butyl, 3,5-di-tert-butyl, 2- Nitro, 4-nitro, 4-nitrylene, 3,4-(methylenedioxy), 4-benzoyl, 4-ethoxycarbonyl, 4-trifluoromethyl, phenyl (can be joined Fused ring compounds: R 7 and R 8 each independently represent 11, a hydroxy group, a decyloxy group, a d-do straight or branched fluorenyl group, a substituted or unsubstituted C 6 -C 18 aryl group, which ⁇ Aryl includes phenyl, 1-naphthyl, 4-tert-butylphenyl, 3,5-di-tert-butylphenyl, 4-methylphenyl,
  • R 9 representatives of H, d-do straight or branched-chain alkyl or alkenyl group, an allyl group, preferably H, methyl, methylene group;
  • R 1Q and R 11 each independently represent 11, a hydroxy group, a decyloxy group, a d-do linear or branched fluorenyl group, a substituted or unsubstituted C 6 -C 18 aryl group, and the aryl group includes a phenyl group, a 1-naphthyl group, and a 4-tert-butyl group.
  • the preparation method of the azacarbene-based palladium catalyst comprises the following steps:
  • the Lewis acid or Brnsted acid described in the step A is selected from one of aluminum trichloride, tin tetrachloride, potassium hydrogen sulfate, formic acid, acetic acid, trifluoroacetic acid and titanium tetraethoxide.
  • the cyclization reaction in the step B is carried out by reacting the glyoxal diimine intermediate compound represented by the formula (11) with paraformaldehyde under the action of the additive (III); the additive (III) is dihydrochloric acid hydrochloride.
  • the palladium in the step C is selected from the group consisting of palladium chloride, palladium acetate, palladium nitrate and palladium acetylacetonate, or a mixture of any two, the inorganic salt (V) being lithium chloride, sodium bromide or iodine. Sodium or sodium acetate, preferably lithium chloride or sodium acetate.
  • the coordination reaction in the step D is carried out under the condition of insulating air, and the alkali required for the alkaline condition is selected from the group consisting of potassium t-butoxide, sodium t-butoxide, potassium hydroxide, sodium ethoxide, potassium carbonate or sodium acetate. .
  • the prepared azacarbene-based palladium catalyst can be used in a coupling reaction of Suzuki-Miyaura, Heck, Buchwald-Hartwig, Kumada-Tamao-Corriu Sonogashira, Negishi, and ⁇ -oxime arylation.
  • the azacarbene-based palladium catalyst is used in the Suzuki-Miyaura reaction to catalyze the cross-coupling reaction of different halogenated aromatic hydrocarbons with arylboronic acid under the action of a base, as shown in formula E:
  • X 1 CI, Br, I, OTf
  • Ar and Ar' each independently represent a substituted or unsubstituted C 6 -C 18 aryl group, a C 4 -C 1() heterocyclic arene, an oxaheteroarene or a thioheteroarene, preferably C1 or Br
  • the base used includes uncle Potassium butoxide, sodium t-butoxide, potassium hydroxide, sodium hydroxide, potassium phosphate, potassium carbonate, sodium carbonate or sodium methoxide.
  • the azacarbene-based palladium catalyst is used in the Heck reaction to catalyze the coupling reaction of different halogenated aromatic hydrocarbons with olefins, as shown in formula F:
  • X 2 CI, Br, I, OTf
  • Ar represents a substituted or unsubstituted C 6 -C 18 aryl group
  • R 12 represents a substituted or unsubstituted C 6 -C 18 aryl group, which comprises a methyl ester, an ethyl ester, an isopropyl ester, a tert-butyl ester.
  • the ester group or the benzyl group or the like, X 2 is preferably C1 or Br.
  • Azacarbene-based palladium catalysts are used in the Buchwald-Hartwig reaction to catalyze the reaction of different halogenated aromatic hydrocarbons with primary or secondary amines under the action of a base, such as formula G;
  • X 3 CI, Br, I, OTf
  • Ar represents a substituted or unsubstituted C 6 -C 18 aryl group
  • R 13 and R 14 each independently represent a fluorenyl or cyclodecyl group of H, C r C 6 , a substituted or unsubstituted C 6 -C 18 aryl, or a six-membered carbocyclic ring, a six-membered oxacarbon ring, a six-membered aza carbon ring
  • X 3 is preferably C1 or Br
  • the base used includes potassium t-butoxide, sodium t-butoxide, Potassium hydroxide, sodium hydroxide, potassium phosphate, potassium carbonate, sodium carbonate or sodium methoxide.
  • the azacarbene-based palladium catalyst is used in the Sonogashira reaction to catalyze the coupling reaction of different halogenated aromatic hydrocarbons with terminal alkynes under the action of a base, as shown by the formula H:
  • R 15 represents a fluorenyl group or a cyclodecyl group of d-do
  • R 16 represents a substituted or unsubstituted C 6 -C 18 aryl group, a linear fluorenyl group of -CH), a branched fluorenyl group or a cyclic fluorene group.
  • the base or alkoxy group, X 4 is preferably Br, and the base used includes potassium t-butoxide, sodium t-butoxide, potassium hydroxide, sodium hydroxide, potassium phosphate, potassium carbonate, sodium carbonate or sodium methoxide.
  • Azacarbene-based palladium catalysts are used in the Kumada-Tamao-Corriu reaction to catalyze the coupling reaction of different halogenated aromatic hydrocarbons with aryl format reagents, as shown in Formula I:
  • X 5 CI, Br, I, OTf
  • Ar represents a substituted or unsubstituted C 6 -C 18 aryl group
  • R 17 represents a substituted or unsubstituted C 6 -C 18 aryl group, a five- or six-membered nitrogen heterocyclic aryl group, five-membered or A six-membered oxygen heterocyclic aryl group or a five-membered sulfur heterocyclic aryl group
  • X 5 is preferably C1 or Br.
  • the azacarbene-based palladium catalyst is used in the Negisln reaction to catalyze the coupling reaction of different halogenated aromatic hydrocarbons with organozinc reagents, as shown in formula J:
  • Ar represents a substituted or unsubstituted C 6 -C 18 aryl group
  • R 18 represents a substituted or unsubstituted C 6 -C 18 aryl group, a benzyl group or a homoallyl group
  • X 6 is preferably a C1 or Br group.
  • Azacarbene-based palladium catalysts are used in the ⁇ -keto arylation reaction to catalyze the reaction of different halogenated aromatic hydrocarbons with ⁇ -ketones, as shown by formula:
  • ⁇ 7 CI, Br, I, OTf
  • Ar represents a substituted or unsubstituted C 6 -C 18 aryl group
  • R 19 represents a substituted or unsubstituted C 6 -C 18 aryl group, a five- or six-membered heterocyclic aryl group, a five-membered or a six-membered oxygen heterocyclic aryl group or a five-membered sulfur heterocyclic aryl group
  • R 2Q represents a linear fluorenyl group, a branched fluorenyl group or a cyclic fluorenyl group of dC 6 wherein R 19 and R 2Q may form a ring
  • X 7 is preferred.
  • the base used for C1 or Br includes potassium t-butoxide, sodium t-butoxide, potassium hydroxide, sodium hydroxide, potassium phosphate, potassium carbonate, sodium carbonate or sodium methoxide.
  • the present invention synthesizes a completely structured azacarbene catalyst having the following characteristics:
  • the catalyst uses a very electron-rich azacarbene as a part of the ligand, which not only improves the activity of the catalyst, but also accelerates the reaction rate of the oxidation addition reaction in the coupling reaction, and benefits from the characteristics of the azacarbene ligand. It also greatly improves the stability of the catalyst to air.
  • an equilibrium ligand of an imine structure is used as a catalyst, and the adjustability of the equilibrium ligand is greatly enriched by modifying the substituent group on the imine benzene ring and changing the substituent group on the imine nitrogen atom. Further adjustment of catalyst activity is possible.
  • the catalyst of the present invention has extremely high catalytic activity, and the catalytic activity can be further adjusted, and thus it can be applied to include Suzuki-Miyaura, Heck, 7 common catalytic coupling reactions such as Buchwald-Hartwig, Kumada-Tamao-Corriu Sonogashira, Negishi and ⁇ - ⁇ arylation reaction.
  • extremely low catalyst dosage less than 500 ppm
  • good results can be obtained, and it has a good industrial application prospect.
  • ⁇ '-bis(2,6-bis(1-phenylpropyl)phenyl)ethenediimide and paraformaldehyde can be reacted under the action of tetrachlorosilane to obtain 1,3-double (2,6-Di(1-phenylpropyl)phenyl)imidazolium chloride.
  • Example 2 45.8 g of tetrachlorosilane (0.27 mol) added in Example 1 was changed to 67.5 mL of 4M. The dioxane hydrochloride solution (0.27 mol of HCl) was kept under the same conditions. After the reaction, the desired product 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride was obtained in a yield of 50%.
  • Example 6 14.9 g of acetophenone methyl hydrazine (0.1 mol) added in Example 6 was changed to 13.5 g of acetophenone oxime (0.1 mol), and the other conditions were unchanged. After the reaction, acetophenone methyl hydrazine was obtained. The palladium ring dimer was 22.4 g in a yield of 80%.
  • NM 500 MHz, Chloroform
  • NM ⁇ 7.82 (s, 1H), 7.68 - 7.55 (m, 2H), 7.55 - 6.72 (m, 2H), 3.37 (s, 3H).
  • Example 6 14.9 g of acetophenone methyl hydrazine (0.1 mol) added in Example 6 was changed to 18.1 g of benzaldehyde phenylimine (0.1 mol), and other conditions were unchanged, and benzaldehyde phenylimine was obtained after the reaction.
  • the palladium ring dimer was 27.3 g in a yield of 84%.
  • Example 6 14.9 g of acetophenone methyl hydrazine (0.1 mol) added in Example 6 was changed to 19.5 g of benzylformaldehyde phenylimine (0.1 mol), and the other conditions were unchanged. After the reaction, benzylformaldehyde phenylimine was obtained. The palladium ring dimer was 24.8 g in a yield of 74%.
  • NM 500 MHz, Chloroform) ⁇ 7.90 (s, 1H), 7.50 - 7.38 (m, 2H), 7.38 - 7.17 (m, 5H), 7.16 - 7.07 (m, 3H), 3.83 (s, 1H).
  • Example 10 29.0 g of acetophenone methyl palladium ring dimer (0.05 mol) added in Example 10 was changed to 27.6 g of acetophenone oxime palladium ring dimer (0.05 mol), and the other conditions were unchanged. After the reaction, a NHC IPr)-acetophenone ruthenium palladium catalyst can be obtained. The product was a yellow powder, 30.4 g, yield 53%.
  • Example 10 29.0 g of acetophenone methyl palladium ring dimer (0.05 mol) added in Example 10 was changed to 32.2 g of benzaldehyde phenylimine palladium ring dimer (0.05 mol), and other conditions were unchanged. After the reaction, an NHC (IPr)-benzaldehyde phenylimine palladium catalyst can be obtained. The product was a yellow powder, 34.3 g, yield 48%.
  • Example 14 The 18.1 g of o-chlorotoluene (0.1 mol) added in Example 14 was changed to 16.2 g of ⁇ -chloronaphthalene (0.1 mol), and the other conditions were unchanged. After purification by column chromatography, the target product was obtained as 17.9 g. The yield was 88%.
  • Example 14 The 18.1 g of o-chlorotoluene (0.1 mol) added in Example 14 was changed to 11.3 g of 3-chloropyridine (0.1 mol), and the other conditions were unchanged. After purification by column chromatography, the target product was obtained by 14.4 g. The yield was 93%.
  • Example 19 14.3 g of p-chloroanisole (0.1 mol) added in Example 19 was changed to 14.1 g of 3,5-dimethylchlorobenzene (0.1 mol), and 12.8 g of t-butyl acrylate (0.1 mol) was added. ) 10.4 g of styrene (0.1 mol) was added instead, and the other conditions were unchanged. After purification by column chromatography, the target product was obtained in an amount of 18.3 g, and the isolated yield was 88%.
  • Example 23 14.2 g of p-chloroanisole (0.1 mol) added in Example 23 was changed to 15.4 g of 2,4,6-trimethylchlorobenzene, and 9.9 g of cyclohexylamine (0.1 mol) was added instead. 9.3 g of aniline (0.1 mol) was added, and the other conditions were unchanged. Purification by column chromatography gave the target product 19.2 g, and the isolated yield was 91%.
  • Example 23 14.2 g of p-chloroanisole (0.1 mol) added in Example 23 was changed to 16.2 g of 1-chloronaphthalene (0.1 mol), and 9.9 g of cyclohexylamine (0.1 mol) was added instead of 7.3.
  • the other conditions of g diethylamine were unchanged, and after purification by column chromatography, the target product was obtained as 16.5 g, and the isolated yield was 83%.
  • Example 27 10.8 g of cyclohexyldecylacetylene (0.1 mol) added in Example 27 was changed to 6.8 g of 1-pentyne, and the other conditions were unchanged. Purification by column chromatography gave 7.8 g of the desired product. 57%.
  • Example 24 16.2 g of 1-chloronaphthalene (0.1 mol) added in Example 24 was changed to 14.1 g of 2,6-dimethylchlorobenzene (0.1 mol), and 13.4 g of phenylethyl ketone (0.1 mol) was added. ) 14.6 g of 1-tetralone (0.1 mol) was added instead, and the other conditions were unchanged. After purification by column chromatography, the target product was 19.5 g, and the isolated yield was 78%.

Abstract

涉及氮杂卡宾类钯催化剂及其制备方法和应用，以乙二醛为原料在路易斯酸或者布朗斯特酸参与的条件下合成乙二醛二亚胺，然后与多聚甲醛反应得到氮杂卡宾类配体；同时钯（II）与含碳氮双键的化合物反应得到钯（II）环二聚体；该钯环二聚体与氮杂卡宾类配体配位后得到氮杂卡宾类钯催化剂。制备得到的全新结构的钯催化剂具有高活性以及多功能的特点，在Suzuki-Miyaura、Heck、Buchwald-Hartwig、Kumada-Tamao-Corriu、Sonogashira、Negishi以及α-酮芳基化反应等多种催化偶联反应中具有优异的反应活性，有些反应甚至能在极低的催化剂浓度下进行，具有较好的产业化前景。

Description

一种氮杂卡宾类钯催化剂及其制备方法和应用 技术领域
本发明涉及新型结构的钯催化剂及其制备和用途，特别涉及一种全新结构、 多功能、 高活性氮杂卡宾 (NHC)类钯催化剂及其制备，以及其在多种偶联反应中 的用途。 背景技术
过渡金属催化的 C-C键偶联反应是一种非常有效的有机合成手段， 通过该 手段能在相对温和的条件下实现特定位置上 C-C键的形成。 因而可以用于多种 天然产物、 药物中间体、 有机材料的合成中， 无论在学术研究中还是产业化开 发上都具有重要意义。 而其中过渡金属钯催化的交叉偶联反应发展尤为迅速 {Org. Process Res. Dev. 2005, 9, 253)。
多年来， 有机金属钯催化剂不断地被开发使得过渡金属催化的 C-C键偶联 反应发生革命性变化。 在这些新型催化剂的作用下， 卤代芳烃、 类卤代芳烃、 烯基卤化物等都能够很好地与各种烯烃、 炔烃、 芳香类化合物或有机金属试剂 进行偶联反应。 广泛的官能团容忍性以及温和的反应条件展示了良好的产业化 潜力。 但是如何将催化剂用量降低却是一个至关重要的问题。
从已有的文献报道看 (C/^m. Rev. 2002, 102, 1359; ) , 绝大多数的交叉偶联 反应采用 1%-10%的催化剂用量（[/S. Patent 2004,002,489, 2002; JP. Patent 2004,262,832, 2003; JP. Patent 2005,008,578, 2003; WO. Patent 2004,101 ,581 , 2004; WO. Patent 2005,012,271 , 2004等等；)。 然而， 催化剂的用量若不能降到 lOOOppm一下， 无论从生产成本还是从最终产品中重金属残留指标的控制上来 讲都将对其产业化产生极大负面影响 (C m. Rev. 2006， 106, 2651)。 为数不多的 微量钯催化剂实现偶联反应的文献及专利摘录如下：
1991年， Syntec报道了利用三硅基膦作为配体， 在 1000 ppm的醋酸钯催 化下实现溴代芳烃与胺的 Buchwald反应， 产率可达 91%， 唯一的不足是其配 体需要用 1 mol%(Z) . Patent 19,963,009， 1991)。 Pb(OAc)2 (0.1 mol%)
P(SiMe3)3 (1 mol%)
Ph-Br
120 °C, 3 h
91 %
1996年， Hoechst发表了关于微量钯催化剂实现 Heck反应的专利， 针对几 种不同的底物， 均能以 500 ppm的催化剂用量实现较高产率的转化 ( ) . Patent 19,647,584， 1996)。
Figure imgf000003_0001
cat OAc X=CI; R=OMe yield=90%
-Pd X=Br; R=CHO yield=72%
-P('Bu)2 X=Br; R=CH3CO yield=98%
2001年， OMG和 Beller共同开发了一类新型钯烯烃配位的催化剂用于氯 代芳烃与硼酸的 Suzuki偶联反应。该类催化剂
行反应， 在 500 ppm催化剂的用量下， 反应的产率就可以达到 90%以上。 而用 对氯氟苯以及对氯苯甲醚作为底物进行反应时， 则效果非常一般 (：^ Patent 1 ,199,292, 2001)。
Figure imgf000003_0002
2008年， Hartwig等人报道了基于二茂铁结构的配体， 配合醋酸钯使用仅 需 50-2000 ppm的催化剂就可以用量催化碘代芳烃、 溴代芳烃甚至是氯代芳烃 的 Buchwald-Hartwig反应，反应产率均可达到 90%以上 ( . Am. Chem. Soc. 2008, 130, 6586)。
Figure imgf000003_0003
由此可见， 交叉偶联反应的产业化应用极其依赖于高效催化剂的合成， 无 论是在原有催化剂基础上进行改进还是发明全新结构的催化剂都具有重要意 义。
发明内容
本发明的目的就是为了克服上述现有技术存在的缺陷而提供一种全新结构 的、 多功能、 高活性氮杂卡宾 (NHC)类钯催化剂及其制备方法和应用， 尤其是 能在低于 500ppm的用量下催化实现 Suzuki-Miyaura、 Heck, Buchwald-Hartwig, Kumada-Tamao-Corriu Sonogashira、 Negishi以及 α-酉同芳基化反应等 7禾中催化 交叉偶联反应。
本发明的目的可以通过以下技术方案来实现：
氮杂卡宾类钯催化剂， 分子结构如下所示：
Figure imgf000004_0001
上述分子结构中 R R2、 R3、 R4和 R5分别独立地代表11、 垸基、 杂垸基 或芳基， R6、 R7和 R8分别独立地代表 H、 垸基、 杂垸基或芳基， R9代表垸基 或芳基烯基， R1Q和 R11分别独立地代表 H、 垸基、 杂垸基或芳基， Y代表 C1 或 OAc。。
所述的 R R3和 R5分别独立地代表 H、 d-C15直链或支链垸基， CrC15 含氮、 氧杂的直链或支链垸基， 芳烃， 优选 H、 d-do的直链或支链垸基以及 d-do含氮、 氧杂的直链或支链垸基；
所述的 Crdo的直链或支链垸基以及 d-do含氮、 氧杂的直链或支链垸基 包含 H、 甲基、 乙基、 异丙基、 异丁基、 1-乙基丙基、 1-苯基丙基、 环己基、 氮二甲基、 氮二乙基、 甲氧基、 乙氧基。
作为优选的实施方式， R6代表苯环上不同位置的取代基包含 H、 F、 2-甲基、 4-甲基、 3,5-二甲基、 2-甲氧基、 4-甲氧基、 3,5二甲氧基、 4-叔丁基、 3,5-二叔 丁基、 2-硝基、 4-硝基、 4-腈基、 3,4- (亚甲二氧基)、 4-苯甲酰基、 4-乙氧羰基、 4-三氟甲基、 苯基 (可连成稠环化合物: R7和 R8分别独立地代表11、 羟基、 垸 氧基、 d-do直链或支链垸基、 取代或未被取代的 C6-C18芳基， 该^^^芳基 包括苯基、 1-萘基、 4-叔丁基苯基、 3,5-二叔丁基苯基、 4-甲基苯基、 3,5-二甲 基苯基、 4,4'-联苯基或 3,5-二苯基苯基。
作为优选的实施方式， R9代表 H、 d-do直链或支链垸基或者烯基、 烯丙 基，优选 H、 甲基、 甲烯基； R1Q和 R11分别独立地代表11、羟基、垸氧基、 d-do 直链或支链垸基、 取代或未被取代的 C6-C18芳基， 该 ^ ^芳基包括苯基、 1- 萘基、 4-叔丁基苯基、 3,5-二叔丁基苯基、 4-甲基苯基、 3,5-二甲基苯基、 4,4'- 联苯基或 3,5-二苯基苯基。
氮杂卡宾类钯催化剂的制备方法包括以下歩骤：
A、 以乙二醛为原料， 与式 (I)所示的伯胺化合物在路易斯酸或者布朗斯特 酸参与的条件下反应得到式 (ID所示的乙二醛二亚胺中间体化合物；
Figure imgf000005_0001
(I) (Π)
B、 式 (11)所示的乙二醛二亚胺中间体化合物与多聚甲醛在添加剂 (III)作用 下环 (IV)所示的氮杂卡宾类化合物；
Figure imgf000005_0002
(Π) (IV)
C、 钯 (π)与式 (VI)或 (VII)所示含碳氮双键的化合物在无机盐 (V)的作用下分 别得到式 (VIII)或者式 (IX)所示的钯 环二聚体；
Figure imgf000006_0001
(VII) (IX)
D、式 (VIII)或者式 (IX)所示的钯 环二聚体与式 (IV)所示的氮杂卡宾类化合 物在
Figure imgf000006_0002
(X)
Figure imgf000007_0001
歩骤 A中所述的路易斯酸或者布朗斯特酸选自三氯化铝、 四氯化锡、 硫酸 氢钾、 甲酸、 乙酸、 三氟乙酸和四乙氧基钛中的一种。
歩骤 B 中的环合反应由式 (11)所示的乙二醛二亚胺中间体化合物与多聚甲 醛在添加剂 (III)的作用下反应；所述的添加剂 (III)为盐酸二氧六环溶液或者三甲 基氯硅垸， 优选三甲基氯硅垸。
歩骤 C中的钯 选自氯化钯、 醋酸钯、 硝酸钯和乙酰丙酮钯中的一种或者 任意两种的混合物， 所述的无机盐 (V)为氯化锂、 溴化钠、 碘化钠或醋酸钠， 优 选氯化锂或醋酸钠。
歩骤 D中的配位反应在隔绝空气的条件下进行，碱性条件需要的碱选自叔 丁醇钾、 叔丁醇钠、 氢氧化钾、 乙醇钠、 碳酸钾或醋酸钠中的一种。
制备得到的氮杂卡宾类钯催化剂可以应用在 Suzuki-Miyaura、 Heck , Buchwald-Hartwig、 Kumada-Tamao-Corriu Sonogashira、 Negishi以及 α-酉同芳基 化的偶联反应中。
氮杂卡宾类钯催化剂应用于 Suzuki-Miyaura反应中， 在碱的作用下催化不 同卤代芳烃与芳基硼酸的交叉偶联反应， 如式 E所示：
cat. (X) or (XI)
Ar-X1 + (HO)2B-Ar， Ar-Ar' 式 E
Base
X1= CI, Br, I, OTf
式 E中 Ar、 Ar'分别独立地代表取代或未被取代的 C6-C18芳基， C4-C1()的 杂环芳烃、 氧杂环芳烃或者硫杂环芳烃， 优选 C1或 Br, 使用的碱包括叔 丁醇钾、 叔丁醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。 氮杂卡宾类钯催化剂应用于 Heck反应中， 催化不同卤代芳烃与烯烃的偶 联反应， 如式 F所示：
=\ cat. (X) or (XI) Ar、
Ar-X2 R 12
?12 式 F
X2= CI, Br, I, OTf
式 F中 Ar代表取代或未被取代的 C6-C18芳基， R12代表取代或未被取代的 C6-C18芳基， 包含甲酯、 乙酯、 异丙酯、 叔丁酯在内的酯基或苄基等， X2优选 C1或 Br。
氮杂卡宾类钯催化剂应用于 Buchwald-Hartwig反应中， 在碱的作用下催化 不同卤代芳烃与一级或二级胺反应， 如式 G所； /」、:
Ar-X3 + H 式 G
Figure imgf000008_0001
X3= CI, Br, I, OTf
式 G中 Ar代表取代或未被取代的 C6-C18芳基， R13、R14分别独立地代表 H， CrC6的垸基或环垸基， 取代或未被取代的 C6-C18芳基， 或是连成六元碳环、六 元氧杂碳环、 六元氮杂碳环， X3优选 C1或 Br, 使用的碱包括叔丁醇钾、 叔丁 醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。
氮杂卡宾类钯催化剂应用于 Sonogashira反应中，在碱的作用下催化不同卤 代芳烃与末端炔烃的偶联反应， 如式 H所示：
cat. (X) or (XI)
R15-X4 + H-= Ar —- R16 式 H
Cul or CuBr
X4= CI, Br, I, OTf
式 G中 R15代表 d-do的垸基、环垸基， R16代表取代或未被取代的 C6-C18 芳基， -CH)的直链垸基、 支链垸基或环垸基或垸氧基， X4优选 Br, 使用的碱 包括叔丁醇钾、 叔丁醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或 甲醇钠。
氮杂卡宾类钯催化剂应用于 Kumada-Tamao-Corriu反应中， 催化不同卤代 芳烃与芳基格式试剂的偶联反应， 如式 I所示：
cat. (X) or (XI)
Ar-X5 + R17-MgBr Ar-R 式 I
X5= CI, Br, I, OTf 式 I中 Ar代表取代或未被取代的 C6-C18芳基， R17代表取代或未被取代的 C6-C18芳基、 五元或六元氮杂环芳基， 五元或六元氧杂环芳基或五元硫杂环芳 基， X5优选 C1或 Br。
氮杂卡宾类钯催化剂应用于 Negisln反应中， 催化不同卤代芳烃与有机锌 试剂的偶联反应， 如式 J所示：
cat. (X) or (XI)
Ar-X6 R18-ZnCI Ar --RR18 式 J
X6= CI, Br, I, OTf
式 J中 Ar代表取代或未被取代的 C6-C18芳基， R18代表取代或未被取代的 C6-C18芳基、 苄基或高烯丙基， X6优选 C1或 Br。
氮杂卡宾类钯催化剂应用于 α-酮芳基化反应中， 催化不同卤代芳烃与 α- 酮反应， 如式 Κ所示：
Ar-X7 + 式 K
Figure imgf000009_0001
Χ7= CI, Br, I, OTf
式 K中 Ar代表取代或未被取代的 C6-C18芳基， R19代表取代或未被取代的 C6-C18芳基、 五元或六元氮杂环芳基、 五元或六元氧杂环芳基或五元硫杂环芳 基， R2Q代表 d-C6的直链垸基、 支链垸基或环垸基， 其中 R19与 R2Q可以连成 环， X7优选 C1或 Br， 使用的碱包括叔丁醇钾、 叔丁醇钠、 氢氧化钾、 氢氧化 钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。
与现有报道的催化剂相比， 本发明合成得到全新结构的氮杂卡宾类催化剂 具有以下特点：
(1) 高活性。本催化剂采用了非常富电子的氮杂卡宾作为其中一部分配体， 不仅提高了催化剂的活性， 加快偶联反应中氧化加成歩骤的反应速率， 同时得 益于氮杂卡宾类配体的特性，还大大提高催化剂对于空气的稳定性。另一方面， 首次采用亚胺类结构作为催化剂的平衡配体， 通过修饰亚胺苯环上的取代基团 以及改变亚胺氮原子上取代基团， 大大丰富平衡配体的可调节性， 为进一歩调 节催化剂活性提供可能。
(2)多功能性。 正是由于本发明的催化剂具有极高的催化活性， 而且催化活 性还能进一歩调整， 因而可以适用于包括 Suzuki-Miyaura、 Heck、 Buchwald-Hartwig、 Kumada-Tamao-Corriu Sonogashira、 Negishi以及 α-酉同芳基 化反应等 7种常见催化偶联反应。特别是在极低催化剂用量 (小于 500 ppm)的条 件下也能取得较好的效果， 具有较好的工业化应用前景。 具体实施方式
下面结合具体实施例对本发明进行详细说明。
实施例 1
Ν,Ν'-双 (2,6-二异丙基苯基)乙垸二亚胺的合成：
在反应器中加入 36.3 g乙二醛 (0.25 mol, 40%水溶液：)， 乙醇 350 mL， 再加 入 88.5 g的 2,6-二异丙基苯胺 (0.5 mol)以及 1.15 g甲酸 (0.025 mmol), 在环境温 度下 (15-20°C;>搅拌反应 3小时。 将反应液过滤， 同时用 150 mL的甲醇洗涤滤 饼， 然后将滤饼干燥至恒重， 即可得到 Ν,Ν'-双 (2,6-二异丙基苯基)乙垸二亚胺。 产品为亮黄色固体， 85.1 g， 产率 91%。 NM (500 MHz, Chloroform) δ 8.41 (s, 2Η), 7.46 (t, J = 7.5 Hz, 2H), 7.21 (d, J = 7.5 Hz, 4H), 3.00 (hept, J = 6.3 Hz, 4H); 1.21 (d, J = 6.4 Hz, 24H；)。重复上述过程， 制备出足够量的 Ν,Ν'-双 (2,6-二异丙基 苯基)乙垸二亚胺产品备用。
1,3-双 (2,6-二异丙基苯基)氯化咪唑的合成：
反应器中加入 8.1 g多聚甲醛 (0.27 mol), 101.5 g Ν,Ν'-双 (2,6-二异丙基苯基) 乙垸二亚胺 (0.27 mol)以及 1.5 L乙酸乙酯溶液， 加热至 70°C搅拌均匀。 然后缓 慢滴加 45.8 g四氯硅垸 (0.27 mol), 滴加时间控制在 45分钟至 1小时， 继续搅 拌反应 3小时。 将反应液过滤， 同时用 200 mL乙酸乙酯洗涤滤饼， 将滤饼干 燥至恒重， 即可得到目标产物 1,3-双 (2,6-二异丙基苯基：)氯化咪唑。 产品为灰白 色固体， 97.4 g，产率 85%。 ifi NM (500 MHz, Chloroform) δ 10.04 (s, 2Η), 8.14 (s, 2H), 7.58 (t, J = 8.0 Hz, 2H), 7.36 (d, J = 7.5 Hz, 4H), 2.43 - 2.49 (m, 4H), 1.30 (d, J = 6.5 Hz, 12H), 1.25 (d, J = 7.0 Hz, 12H)。 重复上述过程， 制备出足够量的 1,3-双 (2,6-二异丙基苯基：)氯化咪唑可作为催化剂的 NHC配体。
实施例 2
将实施例 1中所加入的 88.5 g 2,6-二异丙基苯胺 (0.5 mol)改为加入 67.5 g 2,4,6-三甲基苯胺 (0.5 mol), 其它条件也不变， 经反应后可得到 Ν,Ν'-双 (2,4,6-三 甲基苯基）乙垸二亚胺 64.3 g， 产率为 88%。 NM (500 MHz, Chloroform) δ 7.92 (s, 2H), 7.00 (s, 4H), 2.45 (s, 12H), 2.37 (s, 6H)。
利用得到的 Ν,Ν'-双 (2,4,6-三甲基苯基：)乙垸二亚胺与多聚甲醛在四氯硅垸 作用下反应可以得到 1,3-双 (2,4,6-三甲基苯基；)氯化咪唑。 NM (500 MHz, Chloroform) δ 6.68 (s, 4H), 5.56 (s, 2H), 4.02 (s, 1H), 2.34 (s, 6H), 2.26 (s, 12H)。可 作为催化剂的 NHC配体。
实施例 3
将实施例 1中所加入的 88.5 g 2,6-二异丙基苯胺 (0.5 mol)改为加入 164.5g 2,6-二 (1-苯基丙基)苯胺 (0.5 mol), 其它条件也不变， 经反应后可得到 Ν,Ν'-双 (2,6-二 (1-苯基丙基)苯基)乙垸二亚胺 147.9 g， 产率为 87%。 NM (500 MHz, Chloroform) δ 8.61 (s, 2H), 7.48 (t, J = 7.4 Hz, 2H), 7.34 - 7.23 (m, 20H), 7.22 (t, J = 6.9 Hz, 4H), 4.13 (t, J = 7.2 Hz, 4H), 1.96 (dd, J = 11.4, 4.5 Hz, 4H), 1.92 (dd, J = 11.3, 4.5 Hz, 4H), 1.03 (t, J = 6.7 Hz, 12H)。
利用得到的 Ν,Ν'-双 (2, 6-二 (1-苯基丙基)苯基)乙垸二亚胺与多聚甲醛在四 氯硅垸作用下反应可以得到 1,3-双 (2,6-二 (1-苯基丙基)苯基)氯化咪唑。 NM (500 MHz, Chloroform) δ 7.61 - 7.20 (m, 21H), 7.13 (d, J = 7.3 Hz, 4H), 7.05 (dd, J = 8.0, 6.8 Hz, 2H), 5.78 (s, 2H), 4.38 (s, 1H), 4.19 - 4.12 (m, 4H), 1.99 - 1.86 (m, 8H), 1.02 (t, J = 6.7 Hz, 12H)。 可作为催化剂的 NHC配体。
实施例 4
将实施例 1 中所加入的 88.5 g 2,6-二异丙基苯胺 (0.5 mol)改为加入 89.5g 2,6-二氮二甲基苯胺 (0.5 mol), 其它条件也不变， 经反应后可得到 Ν,Ν'-双 (2,6- 二氮二甲基苯基）乙垸二亚胺 87.4 g， 产率为 92%。 NM (500 MHz, Chloroform) δ 8.75 (s, 2H), 6.96 (t, J = 7.5 Hz, 3H), 6.16 (d, J = 7.5 Hz, 4H), 3.03 (s: 24H)。
利用得到的 Ν,Ν'-双2,6-二氮二甲基苯基：)乙垸二亚胺与多聚甲醛在四氯硅 垸作用下反应可以得到 1,3-双 (2,6-二氮二甲基苯基：)氯化咪唑。 NM (500 MHz, Chloroform) δ 6.55 (t, J = 7.5 Hz, 2H), 5.96 (d, J = 7.5 Hz, 4H), 5.71 (s, 2H), 4.83 (s, 1H), 3.03 (s, 24H)。 可作为催化剂的 NHC配体。
实施例 5
将实施例 1中所加入的 45.8 g四氯硅垸 (0.27 mol)改为加入 67.5 mL 4M的 盐酸二氧六环溶液 (0.27 mol HC1)， 其它条件不变， 反应后同样可以得到目标产 物 1,3-双 (2,6-二异丙基苯基)氯化咪唑， 产率 50%。
实施例 6
苯乙酮甲基肟钯环二聚体的合成：
反应瓶中加入 17.7 g 氯化钯 (0.1 mol), 8.5 g氯化锂 (0.2 mol)以及 500 mL 甲醇溶液， 搅拌至完全溶解。 然后加入 8.2 g醋酸钠 (0.1 mol)以及 14.9 g苯乙酮 甲基肟 (0.1 mol), 在环境温度下 (15-20°C)搅拌反应 3天。 将反应液过滤， 同时 用 100 mL的甲醇洗涤滤饼， 然后将滤饼干燥至恒重， 即可得到苯乙酮甲基肟 钯环二聚体。 产品为黄绿色粉末， 23.9 g， 产率为 83%。 1H NM (500 MHz, Chloroform) δ 7.82 - 7.80 (m, 2H), 7.57 - 7.46 (m, 4H), 7.18 - 7.05 (m, 2H), 3.98 (s 3H), 3.94 (s, 3H), 2.34 (s, 6H)。
实施例 7
将实施例 6中所加入的 14.9 g苯乙酮甲基肟 (0.1 mol) 改为加入 13.5 g苯乙 酮肟 (0.1 mol)，其它条件不变，经反应后可得到苯乙酮甲基肟钯环二聚体 22.4 g， 产率为 80%。 NM (500 MHz, Chloroform) δ 7.82 (s, 1H), 7.68 - 7.55 (m, 2H), 7.55 - 6.72 (m, 2H), 3.37 (s, 3H)。
实施例 8
将实施例 6中所加入的 14.9 g苯乙酮甲基肟 (0.1 mol) 改为加入 18.1 g苯甲 醛苯亚胺 (0.1 mol), 其它条件不变， 经反应后可得到苯甲醛苯亚胺钯环二聚体 27.3 g， 产率为 84%。 NM (500 MHz, Chloroform) δ 8.90 (s, 1H), 7.59 (dd, J = 17.1, 9.6 Hz, 5H), 7.49 - 7.43 (m, 2H), 7.41 (s, 1H), 7.36 (s, 1H), 7.13 (s, 1H)。
实施例 9
将实施例 6中所加入的 14.9 g苯乙酮甲基肟 (0.1 mol) 改为加入 19.5 g苄甲 醛苯亚胺 (0.1 mol), 其它条件不变， 经反应后可得到苄甲醛苯亚胺钯环二聚体 24.8 g, 产率为 74%。 NM (500 MHz, Chloroform) δ 7.90 (s, 1H), 7.50 - 7.38 (m, 2H), 7.38 - 7.17 (m, 5H), 7.16 - 7.07 (m, 3H), 3.83 (s, 1H)。
实施例 10
NHC(IPr)-苯乙酮甲基肟钯催化剂的合成：
在惰性氛围下，向反应器中加入 29.0 g苯乙酮甲基肟钯环二聚体 (0.05 mol), 5.6 g叔丁醇钾 (0.05 mol), 无水四氢呋喃溶液 230 mL。 再加入 42.5 g的 1,3-双 (2,6-二异丙基苯基：)氯化咪唑 (0.1 mol), 反应液在环境温度下 (15-20°C)搅拌反应 24小时。 将反应液过滤， 用 100 mL的乙酸乙酯洗涤， 合并滤液后除去溶剂并 干燥即得目标产物 NHC(IPr)-苯乙酮甲基肟钯催化剂。产品为亮黄色固体， 30.2 g， 产率为 44%。 NM (500 MHz, Chloroform) δ 7.38 (t, J = 7.8 Hz, 2H), 7.31 - 7.29 (m, 2H), 7.23 (s, 2H), 7.17 - 7.16 (m, 2H), 7.08 - 7.06 (m, 1H), 6.90 (dt, J = 25. 7.5 Hz 2H), 6.70 (d, J = 7.5 Hz, 1H), 3.84 (s, 3H), 3.41 - 3.17 (m, 4H), 2.16 (s, 3H), 1.48 (d, J = 6.5 Hz, 6H), 1.14 (d, J = 7.0 Hz, 6H), 1.00 (d, J = 7.0 Hz, 6H), 0.80 (d, J = 6.5 Hz, 6H)。
实施例 11
NHC(IPr)-苯乙酮肟钯催化剂的合成：
将实施例 10中所加入的 29.0 g苯乙酮甲基肟钯环二聚体 (0.05 mol)改为加 入 27.6 g 苯乙酮肟钯环二聚体 (0.05 mol) , 其它条件不变， 经反应后可得到 NHC IPr)-苯乙酮肟钯催化剂。产品为黄色粉末， 30.4 g， 产率为 53%。 NM (500 MHz, Chloroform) δ 10.46 (s, 1Η), 7.42 (t, J = 7.8 Hz, 2H), 7.32 - 7.31 (m, 2H), 7.24 (s, 2H), 7.20 - 7.19 (m, 2H), 6.93 - 6.88 (m, 2H), 6.80 (dt, J = 7.3, 2.0 Hz 1H), 6.61 (d, J = 7.0 Hz, 1H), 3.24 - 3.09 (m, 4H), 2.06 (s, 3H), 1.46 (d, J = 6.5 Hz, 6H), 1.18 (d, J = 7.0 Hz, 6H), 1.00 (d, J = 7.0 Hz, 6H), 0.81 (d, J = 7.0 Hz, 6H)。
实施例 12
将实施例 10中所加入的 29.0 g苯乙酮甲基肟钯环二聚体 (0.05 mol)改为加 入 32.2 g苯甲醛苯亚胺钯环二聚体 (0.05 mol), 其它条件不变， 经反应后可得到 NHC(IPr)- 苯甲醛苯亚胺钯催化剂。 产品为黄色粉末， 34.3 g， 产率为 48%。 NM (500 MHz, Chloroform) δ 8.68 (s, 1H), 7.44 (dddd, J = 15.5, 9.5, 8.9, 4.4 Hz, 5H), 7.77 - 6.61 (m, 16H), 7.52 - 6.61 (m, 12H), 7.36 - 5.60 (m, 10H), 7.01 (dd, J = 8.0, 7.0 Hz, 2H), 7.07 - 5.60 (m, 5H), 5.73 (s, 2H), 3.23 (hept, J = 6.3 Hz, 4H), 1.47 (d, J = 6.5 Hz, 6H), 1.16 (d, J = 7.0 Hz, 6H), 1.00 (d, J = 7.0 Hz, 6H), 0.80 (d, J = 6.5 Hz, 6H)。
实施例 13
NHC(IMeS)-苯乙酮甲基肟钯催化剂的合成：
将实施例 10中所加入的 42.5 g的 1,3-双 (2,6-二异丙基苯基：)氯化咪唑 (0.1 mol)改为加入 34.9 g的 1,3-双 (2,4,6-三甲基苯基)氯化咪唑， 其它条件不变， 经 反应后可得到 NHC(IMes)-苯乙酮甲基肟钯催化剂。产品为亮黄色固体， 29.0 g， 产率为 44%。 NM (500 MHz, Chloroform) δ 8.51 - 6.88 (m, 4Η), 7.46 (dqd, J = 16.5, 7.5, 1.6 Hz, 2H), 7.46 (dqd, J = 16.5, 7.5, 1.6 Hz, 2H), 6.79 (s, 4H), 5.72 (s, 2H), 3.82 (s, 3H), 3.33 (s, 3H), 2.35 (s, 6H), 2.27 (s, 12H)。
实施例 14
在 Suzuki-Miyaura偶联反应中的应用：
在惰性氛围下，向反应器中加入 12.6 g邻氯甲苯 (0.1 mol), 12.2 g苯硼酸 (0.1 mol), 8.4 g氢氧化钾 (0.15 mol)以及 500ppm 式 PQ或式 所示的氮杂卡宾类钯 催化剂， 以及 10 mL异丙醇。在 80°C下搅拌反应 2小时后停止反应。 除去反应 液的溶剂， 得到粗产品， 气相产率>99%。 柱层析纯化可得目标产物 16.1 g， 分 离产率 95%。 NM (500 MHz, Chloroform) δ 7.63 (s, 1H), 7.46 (t, J = 8.8 Hz, 3H), 7.39 - 7.30 (m, 5H), 2.23 (s, 3H)。
实施例 15
将实施例 14中所加入的 18.1 g邻氯甲苯 (0.1 mol)改为加入 22.2 g对氯三氟 甲苯 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 21.5 g， 分离产率 97%。 NM (500 MHz, Chloroform) δ 7.79 - 7.62 (m, 4H), 7.52 - 7.36 (m, 5H)。
实施例 16
将实施例 14中所加入的 18.1 g邻氯甲苯 (0.1 mol)改为加入 16.2 g的 α-氯萘 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 17.9 g， 分离产率 88%。 JH NMR (500 MHz, Chloroform) δ 8.58 (m, 1H), 8.24 (dd, J = 7.5, 1.4 Hz, 1H), 7.89 (m, 3H), 7.76 (m, 3H), 7.69 (d, J = 7.5 Hz, 1H), 7.40 (m, 7H)。
实施例 17
将实施例 14中所加入的 18.1 g邻氯甲苯 (0.1 mol)改为加入 11.3 g的 3-氯吡 啶 (0.1 mol),其他条件不变，柱层析纯化后可得目标产物 14.4 g，分离产率 93%。 JH NMR (500 MHz, Chloroform) δ 8.94 (d, J = 1.3 Hz, 1H), 8.58 (dd, J = 7.5, 1.3 Hz, 1H), 8.24 (dt, J = 7.5, 1.6 Hz, 1H), 7.46 (m, 6H)。
实施例 18
将实施例 14中所加入的 12.2 g苯硼酸O.1 mol)改为加入 15.0 g 3,5-二甲基 苯硼酸 (O.l mol), 其他条件不变， 柱层析纯化后可得目标产物 18.2 g， 分离产率 93%。 NM (500 MHz, Chloroform) δ 7.68 (d, J = 1.4 Hz, 2H), 7.54 (d, J = 7.5 Hz, 2H), 7.40 (t, J = 1.4 Hz, 1H), 7.19 (d, J = 7.5 Hz, 2H), 2.44 (s, 6H), 2.42 (s, 3H)。
实施例 19
在 Heck反应中的应用：
在惰性氛围下， 向反应器中加入 14.3 g对氯苯甲醚 (0.1 mol), 12.8 g丙烯酸 叔丁酯 (0.1 mol), 再加入 500ppm式 (X)或式 (XI)所示的氮杂卡宾类钯催化剂以 及 lO mL N, N-二甲基乙酰胺。 在 120°C下搅拌反应 10小时。 除去反应液的溶 剂，得到粗产品。柱层析纯化可得目标产物 19.2 g，分离产率 82%。 ^ NM OO MHz, Chloroform) δ 7.84 (d, J = 7.5 Hz, 2H), 7.69 (d, J = 15.0 Hz, 1H), 7.22 (d, J = 7.5 Hz, 2H), 6.45 (d, J = 15.2 Hz, 1H), 3.87 (s, 3H), 1.47 (s, 9H)。
实施例 20
将实施例 19中所加入 12.8 g丙烯酸叔丁酯 (0.1 mol)改为加入 8.6 g丙烯酸 甲酯 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 16.3 g， 分离产率 85%。 NM (500 MHz, Chloroform) δ 7.84 (d, J = 7.5 Hz, 2H), 7.69 (d, J = 15.0 Hz, 1H), 7.22 (d, J = 7.3 Hz, 2H), 6.45 (d, J = 15.2 Hz, 1H), 3.87 (s, 3H), 3.84 (s, 3H)。
实施例 21
将实施例 19中所加入的 14.3 g对氯苯甲醚 (0.1 mol)改为加入 14.1 g 3,5-二 甲基氯苯 (0.1 mol),所加入的 12.8 g丙烯酸叔丁酯 (0.1 mol)改为加入 10.4 g苯乙 烯 (0.1 mol),其他条件不变，柱层析纯化后可得目标产物 18.3 g，分离产率 88%。 JH NMR (500 MHz, Chloroform) δ 7.63 (dd, J = 7.5, 1.3 Hz, 2H), 7.42 (t, J = 7.5 Hz: 2H), 7.32 - 7.23 (m, 1H), 7.22 - 7.14 (m, 4H), 2.43 (s, 6H)。
实施例 22
将实施例 19中所加入的 14.3 g对氯苯甲醚 (0.1 mol)改为加入 16.2 g的 α- 氯萘 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 20.1 g， 分离产率为 79%。 NM (500 MHz, Chloroform) δ 7.99 (m, 1H), 7.87 (m, 2H), 7.73 (m, 3H), 7.61 (td, J = 7.5, 1.4 Hz, 1H), 7.44 (td, J = 7.5, 1.4 Hz, 1H), 6.41 (d, J = 15.0 Hz, IH), 1.48 (s, 9H)。
实施例 23
在 Buchwald-Hartwig反应中的应用：
在惰性氛围下， 向反应器中加入 14.2 g对氯苯甲醚 (0.1 mol), 9.9 g环己基 胺 (0.1 mol)， 16.8 g叔丁醇钾 (0.15 mol)， 再加入 500ppm式 (X)或式 (XI)所示的 氮杂卡宾类钯催化剂以及 15 mL N, N-二甲基甲酰胺溶液。在 80°C下搅拌反应 5 小时。 除去反应液的溶剂， 得到粗产品。 柱层析纯化可得目标产物 17.4 g， 分 离产率 85%。 NM (500 MHz, Chloroform) δ 6.70 (m, 4H), 3.89 (s, IH), 3.87 (s, 3H), 3.01 (p, J = 7.3 Hz, IH), 1.94 (dt, J = 7.3, 5.7 Hz, 2H), 1.73 (m, 3H), 1.37 (m, 5H)。
实施例 24
将实施例 23中所加入的 14.2 g对氯苯甲醚 (0.1 mol) 改为加入 15.4 g 2,4,6- 三甲基氯苯，所加入的 9.9 g环己基胺 (0.1 mol)改为加入 9.3 g苯胺 (0.1 mol),其 他条件不变， 柱层析纯化后可得目标产物 19.2 g， 分离产率 91%。 ^ NM OO MHz, Chloroform) δ 7.32 (dd, J = 16.1, 8.6 Hz, 3H), 7.14 (dd, J = 7.5, 1.4 Hz, 2H), 6.95 (tt, J = 7.6, 1.4 Hz, IH), 6.83 (s, 2H), 2.35 (s, 3H), 2.20 (s, 6H)。
实施例 25
将实施例 23中所加入的 9.9 g环己基胺 (0.1 mol) 改为加入 8.7 g吗啉 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 17.0 g， 分离产率 88%。 NM (500 MHz, Chloroform) δ 6.87 (d, J = 7.5 Hz, IH), 6.70 (d, J = 7.5 Hz, IH), 3.85 (dd, J = 12.8, 6.5 Hz, 4H), 3.46 (t, J = 6.2 Hz, IH), 3.14 (t, J = 6.1 Hz, 1H)。
实施例 26
将实施例 23中所加入的 14.2 g对氯苯甲醚 (0.1 mol)改为加入 16.2 g的 1- 氯萘 (0.1 mol), 所加入的 9.9 g环己基胺 (0.1 mol) 改为加入 7.3 g二乙胺其他条 件不变，柱层析纯化后可得目标产物 16.5 g，分离产率 83%。 ^ NM CSOO MHz, Chloroform) δ 8.31 (m, IH), 7.64 (m, 4H), 7.40 (m, IH), 7.20 (m, IH), 3.72 (q, J = 6.3 Hz, 2H), 3.56 (q, J = 6.2 Hz, 2H), 1.21 (t, J = 6.3 Hz, 6H)。
实施例 27
在 Sonogashira反应中的应用： 在惰性氛围下， 向反应器中加入 14.9 g环戊垸基溴 (O.l mol), 10.8 g环己垸 基乙炔 (0.1 mol)， 29.0 g碳酸铯 (0.15 mol)， 再加入 500ppm式 (X)或式 (XI)所示 的氮杂卡宾类钯催化剂， 2000ppm的碘化铜以及 15 mL N, N-二甲基甲酰胺溶 液。 在 60°C下搅拌反应 10小时。 除去反应液的溶剂， 得到粗产品。 柱层析纯 化可得目标产物 8.4 g，分离产率为 48%。 NM (500 MHz, Chloroform) δ 2.55 (m, 1H), 2.47 (pd, J = 7.8, 2.6 Hz, 1H), 2.01 (dt, J = 7.9, 5.7 Hz, 2H), 1.77 (m, 9H), 1.53 (m, 4H), 1.35 (m, 3H)。
实施例 28
将实施例 27中所加入的 10.8 g环己垸基乙炔 (0.1 mol)改为加入 6.8 g的 1- 戊炔， 其他条件不变， 柱层析纯化后可得目标产物 7.8 g， 分离产率 57%。 NM (500 MHz, Chloroform) δ 2.55 (m, 1H), 2.34 (td, J = 5.4, 2.5 Hz, 2H), 1.80 (dddd, J = 12.0, 9.0, 4.6, 2.0 Hz, 4H), 1.73 (dtd, J = 7.1, 3.8, 1.9 Hz, 2H), 1.68 (m, 2H), 1.54 (tdd, J = 6.9, 3.1, 2.0 Hz, 2H), 1.12 (t, J = 6.6 Hz, 3H)。
实施例 29
将实施例 27中所加入的 14.9 g环戊垸基溴 (0.1 mol)改为加入 17.1 g苄溴 (0.1 mol), 所加入的 10.8 g环己垸基乙炔 (0.1 mol)改为加入 10.2 g苯乙炔 (0.1 mol), 其他条件不变， 柱层析纯化后可得目标产物 13.2 g， 分离产率 69%。 NM (500 MHz, Chloroform) δ 7.52 (m, 2H), 7.37 (m, 3H), 7.21 (m, 5H), 3.77 (s, 2H)。
实施例 30
在 Kumada-Tamao-Corriu反应中的应用：
在惰性氛围下，向反应器中加入 15.5 g 2, 4, 6-三甲基氯苯 (0.1 mol), 35.7 mL 萘基格式试剂 (0.1 mol, 2.8 M的乙醚溶液)， 再加入 500ppm 500ppm式 (X)或式 (XI)所示的氮杂卡宾类钯催化剂以及 10 mL无水四氢呋喃。 在 50°C下搅拌反应 24小时。 除去反应液的溶剂， 得到粗产品。 柱层析纯化可得目标产物 22.6 g， 分离产率为 92%。 NM (500 MHz, Chloroform) δ 7.98 (m, 3H), 7.69 (t, J = 1.5 Hz, 1H), 7.56 (m, 2H), 7.44 (dd, J = 7.4, 1.5 Hz, 1H), 7.03 (s, 2H), 2.83 (s, 6H), 2.52 (s, 3H)。
实施例 31 将实施例 30中所加入的 15.5 g 2, 4, 6-三甲基氯苯 (0.1 mol)改为加入 11 .9 g 2-氯噻吩 (0.1 mol) ,所加入的 35.7 mL萘基格式试剂 (0.1 mol , 2.8 M的乙醚溶液) 改为加入 35.7 mL邻甲氧基苯基格式试剂 (0.1 mol， 2.8 M的乙醚溶液)， 其他条 件不变，柱层析纯化后可得目标产物 13.1 g，分离产率 69%。 ^ NM CSOO MHz, Chloroform) δ 7.76 (dd, J = 7.5, 1.4 Hz, 1H), 7.45 (m, 3H), 7.12 (m, 3H), 3.88 (s, 3H)。
实施例 32
将实施例 30中所加入的 35.7 mL萘基格式试剂 (0.1 mol , 2.8 M的乙醚溶液:) 改为加入 35.7 mL呋喃格式试剂 (0.1 mol , 2.8 M的乙醚溶液)， 其他条件不变， 柱层析纯化后可得目标产物 13.4 g， 分离产率 72%。 1H NM (500 MHz, Chloroform) δ 7.59 (dd, J = 7.5, 1.4 Hz, 1H), 7.04 (s, 2H), 6.93 (dd, J = 7.5, 1.4 Hz, 1H), 6.49 (t, J = 7.4 Hz, 1H), 2.64 (s, 6H), 2.52 (s, 3H)。
实施例 33
在 Negishi反应中的应用：
在惰性氛围下， 向反应器中加入 14.0 g的 2,6-二甲基氯苯 (0.1 mol) , 50 mL 苯基氯化锌的四氢呋喃溶液 (0.1 mol , 2.8 M的四氢呋喃溶液)， 再加入 500ppm 式 (X)或者式 (XI)所示的钯催化剂。 在 25 °C -50 °C下搅拌反应 1-3 小时。 除去反 应液的溶剂， 得到粗产品。 柱层析纯化可得目标产物 14.1 g， 分离产率为 82%。 JH NMR (500 MHz, Chloroform) δ 7.61 (dd, J = 7.5, 1 .4 Hz, 1H), 7.47 (t, J = 7.5 Hz: 1H), 7.21 (d, J = 7.5 Hz, 2H), 6.94 (dd, J = 7.5, 1.6 Hz, 1H), 6.50 (t, J = 7.5 Hz, 1H), 2.63 (s, 6H)。
实施例 34
将实施例 33中所加入的 14.0 g的 2,6-二甲基氯苯 (0.1 mol)改为加入 16.2 g 的氯萘 (0.1 mol) , 其他条件不变， 柱层析纯化后可得目标产物 20.2 g， 分离产率 为 87%。 NM (500 MHz, Chloroform) δ 8.48 (m, 1H), 7.96 (m, 3H), 7.70 (t, J = 7.5 Hz, 1H), 7.41 (m, 3H), 7.21 (d, J = 7.5 Hz, 2H), 2.56 (s, 6H)。
实施例 35
将实施例 33中所加入的 14.0 g的 2,6-二甲基氯苯 (0.1 mol)改为加入 11.2 g 的氯苯 (0.1 mol) , 所加入的 50 mL苯基氯化锌的四氢呋喃溶液 (0.1 mol , 2.8 M 的四氢呋喃溶液)改为加入 50 mL苄基氯化锌的四氢呋喃溶液 (0.1 mol, 2.8 M的 四氢呋喃溶液：)， 其他条件不变， 柱层析纯化后可得目标产物 14.9 g， 分离产率 79%。 NM (500 MHz, Chloroform) δ 7.25 (m, 10H), 3.86 (s, 2H)。
实施例 36
将实施例 33中所加入的 14.0 g的 2,6-二甲基氯苯 (0.1 mol)改为加入 11.2 g 的氯苯 (0.1 mol), 所加入的 50 mL苯基氯化锌的四氢呋喃溶液 (0.1 mol, 2.8 M 的四氢呋喃溶液)改为加入 50 mL高烯丙基氯化锌的四氢呋喃溶液 (0.1 mol, 2.8 M的四氢呋喃溶液：)， 其他条件不变， 柱层析纯化后可得目标产物 9.9 g， 分离 产率 75%。 NM (500 MHz, Chloroform) δ 7.21 (m, 5H), 5.76 (ddt, J = 16.4, 10.1, 6.2 Hz, 1H), 4.99 (m, 2H), 2.59 (t, J = 7.9 Hz, 2H), 2.33 (dd, J = 14.3, 7.7 Hz, 2H)。
实施例 37
在 α-酮芳基化反应中的应用：
在惰性氛围下， 向反应器中加入 16.2 g l-氯萘O.l mol), 13.4 g苯基乙基酮 (0.1 mol), 14.4 g叔丁醇钠， 再加入 500ppm NHC(IPr)-苯乙酮甲基肟钯催化剂 以及 10 mL甲苯， 在 60°C下搅拌反应 10小时。 除去反应液的溶剂， 得到粗产 品。 柱层析纯化可得目标产物 21.8 g， 分离产率为 84%。 1H NMR (500 MHz, Chloroform) δ 7.84 (m, 5H), 7.62 (t, J = 1.4 Hz, 1H), 7.51 (m, 6H), 4.63 (q, J = 6.4 Hz, 1H), 1.70 (d, J = 6.6 Hz, 3H)。
实施例 38
将实施例 24中所加入的 16.2 g 1-氯萘 (0.1 mol)改为加入 14.1 g 2,6-二甲基 氯苯 (0.1 mol),所加入的 13.4 g苯基乙基酮 (0.1 mol)改为加入 14.6 g 1-四氢萘酮 (0.1 mol),其他条件不变，柱层析纯化后可得目标产物 19.5 g，分离产率为 78%。 JH NMR (500 MHz, Chloroform) δ 7.57 (dd, J = 7.4, 1.5 Hz, 1H), 7.39 (td, J = 7.6, 1.8 Hz, 2H), 7.26 (m, 4H), 4.28 (t, J = 8.8 Hz, 1H), 2.81 (m, 2H), 2.40 (s, J = 8.0 Hz, 6H), 2.36 (m, 1H), 2.11 (ddd, J = 12.5, 7.7, 5.3 Hz, 1H)。

Claims

权 利 要 求
1. 钯催化剂， 其特征在于， 该催化剂的分子结构如下所示:
Figure imgf000020_0001
上述分子结构中 R R2、 R3、 R4和 R5分别独立地代表11、 垸基、 杂垸基 或芳基， R6、 R7和 R8分别独立地代表 H、 垸基、 杂垸基或芳基， R9代表垸基 或芳基烯基， R1Q和 R11分别独立地代表 H、 垸基、 杂垸基或芳基， Y代表 C1 或 OAc。
2. 根据权利要求 1所述的氮杂卡宾类钯催化剂， 其特征在于， 所述的 R R3和 R5分别独立地代表11、 d-C15直链或支链垸基， CrC15含氮、 氧杂的直链 或支链垸基， 芳烃， 优选 H、 d-do的直链或支链垸基以及 d-do含氮、 氧杂 的直链或支链垸基；
所述的 Crdo的直链或支链垸基以及 d-do含氮、 氧杂的直链或支链垸基 包含 H、 甲基、 乙基、 异丙基、 异丁基、 1-乙基丙基、 1-苯基丙基、 环己基、 氮二甲基、 氮二乙基、 甲氧基、 乙氧基。
3. 根据权利要求 1所述的氮杂卡宾类钯催化剂， 其特征在于， 所述的 R6 代表苯环上不同位置的取代基包含 H、 F、 2-甲基、 4-甲基、 3,5-二甲基、 2-甲 氧基、 4-甲氧基、 3,5二甲氧基、 4-叔丁基、 3,5-二叔丁基、 2-硝基、 4-硝基、 4- 腈基、 3,4- (亚甲二氧基)、 4-苯甲酰基、 4-乙氧羰基、 4-三氟甲基、 苯基 (可连成 稠环化合物)； R7和 R8分别独立地代表11、 羟基、 垸氧基、 d-do直链或支链 垸基、 取代或未被取代的 C6-C18芳基， 该 C6-C18芳基包括苯基、 1-萘基、 4-叔 丁基苯基、 3,5-二叔丁基苯基、 4-甲基苯基、 3,5-二甲基苯基、 4,4'-联苯基或 3,5- 二苯基苯基。
4. 根据权利要求 1所述的氮杂卡宾类钯催化剂， 其特征在于， 所述的 R9 代表 H、 d-do直链或支链垸基或者烯基、 烯丙基， 优选 H、 甲基、 甲烯基； R1Q和 R11分别独立地代表11、 羟基、 垸氧基、 d-do直链或支链垸基、 取代或 未被取代的 C6-C18芳基， 该 C6-C18芳基包括苯基、 1-萘基、 4-叔丁基苯基、 3,5- 二叔丁基苯基、 4-甲基苯基、 3,5-二甲基苯基、 4,4'-联苯基或 3,5-二苯基苯基。
5. 根据权利要求 1-4中任一项所述氮杂卡宾类钯催化剂的制备方法， 其特 征在于， 该方法包括以下歩骤：
A、 以乙二醛为原料， 与式 (I)所示的伯胺化合物在路易斯酸或者布朗斯特酸参 与的条件下反应得到式 所示的乙二醛二亚胺中间体化合物；
Figure imgf000021_0001
(1) (11)
B、式 (11)所示的乙二醛二亚胺中间体化合物与多聚甲醛在添加剂 (III)作用下环 (IV)所示的氮杂卡宾类化合物；
Figure imgf000021_0002
(Π) (IV)
C、钯 与式 (VI)或 (VII)所示含碳氮双键的化合物在无机盐 (V)的作用下分别得
Figure imgf000021_0003
(VII) (IX) D、 式 (VIII)或者式 (IX)所示的钯 环二聚体与式 (IV)所示的氮杂卡宾类化合物 位得到式 (X)或者式 (XI)所示的氮杂卡宾类钯催化剂；
Figure imgf000022_0001
(XI)
6. 根据权利要求 5所述的氮杂卡宾类钯催化剂的制备方法， 其特征在于， 歩骤 A中所述的路易斯酸或者布朗斯特酸选自三氯化铝、四氯化锡、硫酸氢钾、 甲酸、 乙酸、 三氟乙酸和四乙氧基钛中的一种。
7. 根据权利要求 5所述的氮杂卡宾类钯催化剂的制备方法， 其特征在于， 歩骤 B 中的环合反应由式 (ID所示的乙二醛二亚胺中间体化合物与多聚甲醛在 添加剂 (III)的作用下反应；所述的添加剂 (III)为盐酸二氧六环溶液或者三甲基氯 硅垸， 优选三甲基氯硅垸。
8. 根据权利要求 5所述的氮杂卡宾类钯催化剂的制备方法， 其特征在于， 歩骤 C中的钯 选自氯化钯、 醋酸钯、 硝酸钯和乙酰丙酮钯中的一种或者任意 两种的混合物， 所述的无机盐 (V)为氯化锂、 溴化钠、 碘化钠或醋酸钠， 优选氯 化锂或醋酸钠。
9. 根据权利要求 5所述的氮杂卡宾类钯催化剂的制备方法， 其特征在于， 歩骤 D中的配位反应在隔绝空气的条件下进行，碱性条件需要的碱选自叔丁醇 钾、 叔丁醇钠、 氢氧化钾、 乙醇钠、 碳酸钾或醋酸钠中的一种。
10. 如权利要求 1-4中任一项所述的氮杂卡宾类钯催化剂的应用， 其特征 在于， 制备得到的氮杂卡宾类钯催化剂应用在 Suzuki-Miyaura、 Heck , Buchwald-Hartwig、 Kumada-Tamao-Corriu Sonogashira、 Negishi以及 α-酉同芳基 化的偶联反应中。
11. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Suzuki-Miyaura反应中， 在碱的作用下催化不同卤代 芳烃与芳基硼酸的交叉偶联反应， 如式 E所示：
cat. (X) or (XI)
Ar-X1 + (HO)2B— Ar' *■ Ar-Ar' 式 E
Base
X1= CI, Br, I, OTf
式 E中 Ar、 Ar'分别独立地代表取代或未被取代的 C6-C18芳基， C4-C1Q的氮杂 环芳烃、 氧杂环芳烃或者硫杂环芳烃， 优选 C1或 Br, 使用的碱包括叔丁醇 钾、 叔丁醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。
12. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Heck反应中， 催化不同卤代芳烃与烯烃的偶联反应， 如式 F所示：
cat. (X) or (XI) Ar\
Ar- X2 + R12 式 F
X2= CI, Br, I, OTf
式 F中 Ar代表取代或未被取代的 C6-C18芳基， R12代表取代或未被取代的 C6-C18芳基， 包含甲酯、 乙酯、 异丙酯、 叔丁酯在内的酯基或苄基等， X2优选 C1或 Br。
13. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Buchwald-Hartwig反应中， 在碱的作用下催化不同卤 代芳烃与一级或二级胺反应， 如式 G所示：
R 14
cat. (X) or (XI) R14
Ar-X3 + HN Ar-N 式 G
)13
R13
X3= CI, Br, I, OTf
式 G中 Ar代表取代或未被取代的 C6-C18芳基， R13、R14分别独立地代表 H， CrC6的垸基或环垸基， 取代或未被取代的 C6-C18芳基， 或是连成六元碳环、六 元氧杂碳环、 六元氮杂碳环， X3优选 C1或 Br, 使用的碱包括叔丁醇钾、 叔丁 醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。
14. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Sonogashira反应中，在碱的作用下催化不同卤代芳烃 与末端炔烃的偶联反应， 如式 H所； /」、：
cat. (X) or (XI)
R15—X4 + H_=_R 16 Ar Rib 式 H
Cul or CuBr
X4= CI, Br, I, OTf
式 G中 R15代表 d-do的垸基、环垸基， R16代表取代或未被取代的 C6-C18 芳基， C Cu)的直链垸基、 支链垸基或环垸基或垸氧基， X4优选 Br, 使用的碱 包括叔丁醇钾、 叔丁醇钠、 氢氧化钾、 氢氧化钠、 磷酸钾、 碳酸钾、 碳酸钠或 甲醇钠。
15. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Kumada-Tamao-Corriu反应中， 催化不同卤代芳烃与 芳基格式试剂的偶联反应， 如式 I所； /」、:
cat. (X) or (XI)
Ar— X5 R .MgBr Ar-R 式 I
X5= CI, Br, I, OTf
式 I中 Ar代表取代或未被取代的 C6-C18芳基， R17代表取代或未被取代的 C6-C18芳基、 五元或六元氮杂环芳基， 五元或六元氧杂环芳基或五元硫杂环芳 基， X5优选 C1或 Br。
16. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 Negisln反应中， 催化不同卤代芳烃与有机锌试剂的 偶联反应， 如式 J所示： cat. (X) or (XI)
Ar-X6 R18-ZnCI Ar-R18 式 J
X6= CI, Br, I, OTf
式 J中 Ar代表取代或未被取代的 C6-C18芳基， R18代表取代或未被取代的 C6-C18芳基、 苄基或高烯丙基， X6优选 C1或 Br。
17. 根据权利要求 10所述的氮杂卡宾类钯催化剂的应用， 其特征在于， 氮 杂卡宾类钯催化剂应用于 α-酮芳基化反应中， 催化不同卤代芳烃与 α-酮反应， 如式 Κ所示：
Ar-X7 + 式 K
Figure imgf000025_0001
X7= CI, Br, I, OTf
式 K中 Ar代表取代或未被取代的 C6-C18芳基， R19代表取代或未被取代的 C6-C18芳基、 五元或六元氮杂环芳基、 五元或六元氧杂环芳基或五元硫杂环芳 基， R2Q代表 d-C6的直链垸基、 支链垸基或环垸基， 其中 R19与 R2Q可以连成 环， X7优选 C1或 Br， 使用的碱包括叔丁醇钾、 叔丁醇钠、 氢氧化钾、 氢氧化 钠、 磷酸钾、 碳酸钾、 碳酸钠或甲醇钠。
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