CN104610003B - A method for asymmetrically catalyzing Michael addition with high-efficiency supported catalysts - Google Patents
A method for asymmetrically catalyzing Michael addition with high-efficiency supported catalysts Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 33
- 238000006845 Michael addition reaction Methods 0.000 title claims description 12
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 claims abstract description 47
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 8
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- 239000000654 additive Substances 0.000 claims abstract description 5
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- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 4
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- 238000000926 separation method Methods 0.000 claims description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- UENAIURQSOHLFG-JTQLQIEISA-N (3R)-3-(2-chlorophenyl)-2,2-dimethyl-4-nitrobutanal Chemical compound CC(C)(C=O)[C@@H](C[N+]([O-])=O)c1ccccc1Cl UENAIURQSOHLFG-JTQLQIEISA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
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- 125000004971 nitroalkyl group Chemical group 0.000 description 2
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- MMMWGNYDGZLVQA-OAHLLOKOSA-N (3R)-2,2-dimethyl-3-naphthalen-1-yl-4-nitrobutanal Chemical compound CC(C=O)([C@H](C[N+](=O)[O-])C1=CC=CC2=CC=CC=C12)C MMMWGNYDGZLVQA-OAHLLOKOSA-N 0.000 description 1
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- LWHPRHKYQAEVOH-LLVKDONJSA-N (3r)-2,2-dimethyl-4-nitro-3-(4-nitrophenyl)butanal Chemical compound O=CC(C)(C)[C@H](C[N+]([O-])=O)C1=CC=C([N+]([O-])=O)C=C1 LWHPRHKYQAEVOH-LLVKDONJSA-N 0.000 description 1
- RDPSRQAHEBIFRW-LLVKDONJSA-N (3r)-2,2-dimethyl-4-nitro-3-phenylbutanal Chemical compound O=CC(C)(C)[C@H](C[N+]([O-])=O)C1=CC=CC=C1 RDPSRQAHEBIFRW-LLVKDONJSA-N 0.000 description 1
- RSXVVMJBGJTOMG-MRVPVSSYSA-N (3r)-2,2-dimethyl-4-nitro-3-thiophen-2-ylbutanal Chemical compound O=CC(C)(C)[C@H](C[N+]([O-])=O)C1=CC=CS1 RSXVVMJBGJTOMG-MRVPVSSYSA-N 0.000 description 1
- SYJMYDMKPSZMSB-AATRIKPKSA-N 1,2-dimethoxy-4-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C=C1OC SYJMYDMKPSZMSB-AATRIKPKSA-N 0.000 description 1
- JKQUXSHVQGBODD-VOTSOKGWSA-N 1-(4-Methoxyphenyl)-2-nitroethylene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C=C1 JKQUXSHVQGBODD-VOTSOKGWSA-N 0.000 description 1
- HNRGHIXNKWOUEO-CMDGGOBGSA-N 1-[(e)-2-nitroethenyl]naphthalene Chemical compound C1=CC=C2C(/C=C/[N+](=O)[O-])=CC=CC2=C1 HNRGHIXNKWOUEO-CMDGGOBGSA-N 0.000 description 1
- QHKJTRDWAZGBLR-AATRIKPKSA-N 1-chloro-2-[(e)-2-nitroethenyl]benzene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC=C1Cl QHKJTRDWAZGBLR-AATRIKPKSA-N 0.000 description 1
- YOEGXQQUPVDQEE-UHFFFAOYSA-N 1-nitro-3-(2-nitroethenyl)benzene Chemical compound [O-][N+](=O)C=CC1=CC=CC([N+]([O-])=O)=C1 YOEGXQQUPVDQEE-UHFFFAOYSA-N 0.000 description 1
- HABXLWPUIWFTNM-UHFFFAOYSA-N 1-nitro-4-(2-nitroethenyl)benzene Chemical compound [O-][N+](=O)C=CC1=CC=C([N+]([O-])=O)C=C1 HABXLWPUIWFTNM-UHFFFAOYSA-N 0.000 description 1
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- KSCAZPYHLGGNPZ-UHFFFAOYSA-N 3-chloropropyl(triethoxy)silane Chemical compound CCO[Si](OCC)(OCC)CCCCl KSCAZPYHLGGNPZ-UHFFFAOYSA-N 0.000 description 1
- CTJKRKMPTRJAIT-AATRIKPKSA-N 4-[(e)-2-nitroethenyl]phenol Chemical compound OC1=CC=C(\C=C\[N+]([O-])=O)C=C1 CTJKRKMPTRJAIT-AATRIKPKSA-N 0.000 description 1
- KXIKKCAQRYXRMY-VXGBXAGGSA-N C[n]1c(S(N[C@H](CCCC2)[C@@H]2N)(=O)=O)[n+](CCC[SiH3])cc1 Chemical compound C[n]1c(S(N[C@H](CCCC2)[C@@H]2N)(=O)=O)[n+](CCC[SiH3])cc1 KXIKKCAQRYXRMY-VXGBXAGGSA-N 0.000 description 1
- 241001317416 Lius Species 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000001500 prolyl group Chemical class [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
技术领域technical field
本发明涉及一种高效、绿色的、以水做溶剂条件下，以新型超顺磁纳米负载、离子气氛”修饰的手性小分子为催化剂，N,N-二甲基吡啶(DMAP)为促进剂、25℃、常压下异丁醛与硝基烯烃进行不对称Michael加成反应方法。The invention relates to a high-efficiency, green chiral small molecule modified with new superparamagnetic nano-loading and ion atmosphere under the condition of using water as a solvent, and N,N-lutidine (DMAP) as a catalyst Asymmetric Michael addition reaction method between isobutyraldehyde and nitroalkenes at 25°C and normal pressure.
技术背景technical background
硝基烷烃因为容易进行α-烷基化反应和转化为其它重要官能团，在有机合成中具有重要作用(CzekeliusC,CarreiraEM.Angew.Chem.Int.Ed.,2005,44,612；BernerOM,TedeschiL,EndersD.Eur.J.Org.Chem.,2002,2002,1877.)。以碳为中心的亲核试剂与硝基烯烃的共轭加成是最普遍的制备手性硝基烷烃的方法。其中，最主要的是利用羰基化合物与硝基烯烃的Michael加成反应(BetancortJM,BarbasCF,Org.Lett.,2001,3,3737；MelchiorreP,KA,J.Org.Chem.,2003,68,4151；AustinJF,MacMillanDWC,J.Am.Chem.Soc.,2002,124,1172；DavieEAC,MennenSM,XuY,etal.Chem.Rev.,2007,107,5759.)。Nitroalkanes play an important role in organic synthesis because of their ease of α-alkylation and conversion into other important functional groups (CzekeliusC, CarreiraEM.Angew.Chem.Int.Ed., 2005, 44, 612; BernerOM, TedeschiL, EndersD. Eur. J. Org. Chem., 2002, 2002, 1877.). The conjugate addition of carbon-centered nucleophiles to nitroalkenes is the most common method for the preparation of chiral nitroalkanes. Among them, the most important is the Michael addition reaction (BetancortJM, BarbasCF, Org.Lett., 2001, 3, 3737; MelchiorreP, KA, J.Org.Chem., 2003, 68, 4151; Austin JF, MacMillanDWC, J.Am.Chem.Soc., 2002, 124, 1172; DavieEAC, MennenSM, XuY, etal.Chem.Rev., 2007, 107 ,5759.).
近年来，不对称有机小分子催化引起了化学家们广泛的关注，涌现出了一系列脯氨酸盐、手性金属配位催化剂等，在醛与硝基烯烃的不对称共轭加成中取得了一定的效果(LiH,WangY,TangL,WuF,LiuX,GuoC,FoxmanBM,DengL,Angew.Chem.Int.Ed.,2005,44,105；MalerichJP,HagiharaK,RawalVH,J.Am.Chem.Soc.,2008,130,14416；YuZ,LiuX,ZhouL,LinL,FengX,Angew.Chem.Int.Ed.,2009,48,5195.)。但是上述方法存在着使用大量有毒有害溶剂、使用催化剂回收套用困难等缺陷。因此，非常有必要开发立体催化活性好、回收简单的新型负载催化剂。In recent years, asymmetric organic small molecule catalysis has attracted widespread attention from chemists, and a series of proline salts, chiral metal coordination catalysts, etc. have emerged. Some effects have been achieved (LiH, WangY, TangL, WuF, LiuX, GuoC, FoxmanBM, DengL, Angew.Chem.Int.Ed., 2005, 44, 105; MalerichJP, HagiharaK, RawalVH, J.Am.Chem.Soc., 2008, 130, 14416; YuZ, LiuX, ZhouL, LinL, FengX, Angew.Chem.Int.Ed., 2009, 48, 5195.). However, the above-mentioned method has defects such as the use of a large amount of toxic and harmful solvents, and the difficulty of using catalysts for recovery and application. Therefore, it is very necessary to develop novel supported catalysts with good stereocatalytic activity and easy recovery.
与传统负载聚合物相比，超顺磁纳米颗粒不仅尺寸处于纳米级，保证催化反应，而且容易被外加磁场分离，更好的解决了催化剂的分离与回收。因此近年来，超顺磁纳米颗粒负载催化剂已经成为人们探索环境友好的催化反应体系的重要方向(GawandeMB,BrancoPS,VarmaSV,Chem.Soc.Rev.,2013,42,3371；BaigRBN,VarmaS,Chem.Commun.,2013,49,752)。离子液体具有热力学稳定性、溶解能力强、低挥发性、分子结构可调性等特点。我们结合超顺磁纳米颗粒与离子液体这两者的优势，设计出超顺磁纳米颗粒负载、“离子气氛”修饰的催化剂并成功应用于有机合成中，取得了很好的效果(Ying,A,LiuS,NiY,QiuF,XuS,TangW,Catal.Sci.Technol.,2014,4,2115；YingA,QiuF,WuC,HuH,YangJ.,RSCAdv.,2014,4,33173.)。因此有必要开发超顺磁纳米负载、“离子气氛”修饰的手性催化剂用于不对称Michael加成反应中。Compared with traditional loaded polymers, superparamagnetic nanoparticles not only have a nanoscale size to ensure the catalytic reaction, but also are easily separated by an external magnetic field, which better solves the separation and recovery of catalysts. Therefore, in recent years, superparamagnetic nanoparticle-supported catalysts have become an important direction for people to explore environmentally friendly catalytic reaction systems (GawandeMB, BrancoPS, VarmaSV, Chem.Soc.Rev., 2013, 42, 3371; BaigRBN, VarmaS, Chem. Commun., 2013, 49, 752). Ionic liquids have the characteristics of thermodynamic stability, strong solubility, low volatility, and adjustable molecular structure. Combining the advantages of superparamagnetic nanoparticles and ionic liquids, we designed a catalyst loaded with superparamagnetic nanoparticles and modified with "ionic atmosphere" and successfully applied it in organic synthesis, achieving good results (Ying, A , LiuS, NiY, QiuF, XuS, TangW, Catal. Sci. Technol., 2014, 4, 2115; YingA, QiuF, WuC, HuH, YangJ., RSCAdv., 2014, 4, 33173.). Therefore, it is necessary to develop superparamagnetic nano-supported, "ionic atmosphere" modified chiral catalysts for asymmetric Michael addition reactions.
发明内容Contents of the invention
本发明的目的是取代传统的不对称催化异丁醛与硝基烯烃Michael加成方法，提供一种高效、环境友好的负载手性催化剂，以水做溶剂温和(室温)反应条件下实现Michael加成。The purpose of the present invention is to replace the traditional asymmetric catalytic isobutyraldehyde and nitroolefin Michael addition method, to provide a highly efficient, environmentally friendly loaded chiral catalyst, to achieve Michael addition under mild (room temperature) reaction conditions with water as a solvent. become.
根据本发明，所述通过异丁醛与硝基烯烃进行立体选择性Michael加成的方法，其特征在于，所述方法包括以超顺磁纳米颗粒负载、“离子气氛”修饰的手性小分子为催化剂，室温(25℃)、常压下异丁醛与硝基烯烃进行不对称Michael加成反应，包括：以超顺磁纳米颗粒负载、“离子气氛”修饰手性小分子为催化剂，室温(25℃)、常压下，以水做溶剂，异丁醛与硝基烯烃进行不对称Michael加成反应1～10小时，得到相应的手性硝基取代物。其中，所述催化剂为：According to the present invention, the method for stereoselective Michael addition of isobutyraldehyde and nitroalkenes is characterized in that the method includes chiral small molecules loaded with superparamagnetic nanoparticles and modified by "ionic atmosphere" As a catalyst, asymmetric Michael addition reaction between isobutyraldehyde and nitroalkene is carried out at room temperature (25°C) and normal pressure, including: using superparamagnetic nanoparticles loaded, "ionic atmosphere" modified chiral small molecules as catalysts, at room temperature (25° C.), under normal pressure, using water as a solvent, carry out asymmetric Michael addition reaction between isobutyraldehyde and nitroalkene for 1 to 10 hours to obtain the corresponding chiral nitro substituted product. Wherein, the catalyst is:
其中，所述异丁醛与硝基烯烃的摩尔比为1:1-10:1。Wherein, the molar ratio of isobutyraldehyde to nitroolefin is 1:1-10:1.
其中，所述催化剂的摩尔量为硝基烯烃的0.1-1倍。Wherein, the molar amount of the catalyst is 0.1-1 times that of the nitroolefin.
其中，所述添加剂DMAP的摩尔量为硝基烯烃的0.01-0.5倍。Wherein, the molar amount of the additive DMAP is 0.01-0.5 times that of the nitroolefin.
其中，所述硝基烯烃物质为(I)式结构，其中Ar包括苯、4-硝基苯、3-硝基苯、2-氯苯、4-氯苯、4-甲氧基苯、4-羟基苯、3,4-二甲氧基苯、3-甲氧基-4-羟基苯、1-萘基和2-噻吩。Wherein, the nitroalkene material is (I) formula structure, wherein Ar comprises benzene, 4-nitrobenzene, 3-nitrobenzene, 2-chlorobenzene, 4-chlorobenzene, 4-methoxybenzene, 4 -Hydroxybenzene, 3,4-dimethoxybenzene, 3-methoxy-4-hydroxybenzene, 1-naphthyl and 2-thiophene.
其中，所述反应介质为水。Wherein, the reaction medium is water.
其中，反应结束后，用乙酸乙酯萃取反应液，合并有机相，柱层析分离得到产品。催化剂可由外加磁场回收，乙酸乙酯洗涤后，经过60℃真空干燥5小时后用于下一次套用。Wherein, after the reaction is completed, the reaction solution is extracted with ethyl acetate, the organic phases are combined, and the product is obtained by column chromatography separation. The catalyst can be recovered by an external magnetic field, washed with ethyl acetate, dried in vacuum at 60°C for 5 hours, and used for the next application.
本发明提供的利用新型磁纳米颗粒负载、“离子气氛”修饰的手性小分子立体选择性催化异丁醛与硝基烯烃的Michael的加成方法，是通过以下途径来实现的：The Michael's addition method of isobutyraldehyde and nitroalkene is catalyzed stereoselectively by the chiral small molecule modified by the novel magnetic nanoparticle loading and "ionic atmosphere" provided by the present invention, which is realized through the following ways:
本发明所使用的新型功能离子液体的制备过程：The preparation process of the novel functional ionic liquid used in the present invention:
取1g1，加入50mL无水甲苯，超声1h。加入3-氯丙基三乙氧基硅烷(4g，4mL)，在氮气保护110℃下机械搅拌回流24h。反应液冷却至室温，得到的褐色固体2用磁体收集，用乙醇冲洗，60℃真空干燥10h。取0.3g3，加0.358g3，加入20mL无水甲苯，超声1h，在氮气保护110℃下机械搅拌回流48h。反应液冷却至室温，得到的褐色固体4用磁体收集，用乙醇冲洗，60℃真空干燥10h。将4加入10mL二氯甲烷，1mL三氟乙酸，室温搅拌10h，除去溶剂，所剩固体依次用饱和NaHCO3溶液、水、甲醇冲洗，60℃真空干燥10h得到最终的催化剂。经元素分析，催化剂的有效负载量为0.882mmol/g。Take 1g1, add 50mL of anhydrous toluene, and sonicate for 1h. 3-Chloropropyltriethoxysilane (4 g, 4 mL) was added, mechanically stirred and refluxed at 110° C. for 24 h under nitrogen protection. The reaction liquid was cooled to room temperature, and the obtained brown solid 2 was collected by a magnet, rinsed with ethanol, and dried under vacuum at 60° C. for 10 h. Take 0.3g3, add 0.358g3, add 20mL of anhydrous toluene, sonicate for 1h, mechanically stir and reflux for 48h under nitrogen protection at 110°C. The reaction liquid was cooled to room temperature, and the obtained brown solid 4 was collected by a magnet, rinsed with ethanol, and dried under vacuum at 60° C. for 10 h. Add 10 mL of dichloromethane and 1 mL of trifluoroacetic acid to 4, stir at room temperature for 10 h, remove the solvent, wash the remaining solid with saturated NaHCO 3 solution, water, and methanol successively, and dry it in vacuum at 60°C for 10 h to obtain the final catalyst. According to elemental analysis, the effective loading amount of the catalyst is 0.882mmol/g.
不对称Michael加成产物制备过程是：The preparation process of asymmetric Michael addition products is:
在装有磁力搅拌装置的三口烧瓶中，依次加入异丁醛、硝基烯烃、DMAP和催化剂。其中异丁醛与硝基烯烃的摩尔比为1:1-10:1，催化剂的摩尔量为硝基烯烃的0.1-1倍，添加剂DMAP的摩尔量为硝基烯烃的0.01-0.5倍，以水做溶剂、25℃、常压反应1-10小时，薄层色谱(TLC)跟踪反应进度。反应结束后，用乙酸乙酯萃取反应液，合并有机相，柱层析分离得到产品，萃余相用外加磁体回收催化剂，乙酸乙酯洗涤，60℃真空干燥5小时后用于下一批次反应，催化剂重复使用5次，未发现反应收率明显下降。In a three-neck flask equipped with a magnetic stirring device, sequentially add isobutyraldehyde, nitroolefin, DMAP and catalyst. Wherein the molar ratio of isobutyraldehyde and nitroalkenes is 1:1-10:1, the molar weight of catalyst is 0.1-1 times of nitroalkenes, and the molar weight of additive DMAP is 0.01-0.5 times of nitroalkenes, with Use water as a solvent, react at 25°C and normal pressure for 1-10 hours, and track the progress of the reaction by thin layer chromatography (TLC). After the reaction, the reaction solution was extracted with ethyl acetate, the organic phases were combined, and the product was separated by column chromatography. The raffinate phase was recovered with an external magnet, washed with ethyl acetate, dried in vacuum at 60°C for 5 hours, and then used for the next batch Reaction, catalyzer is reused 5 times, does not find reaction yield to decline obviously.
具体实施方式detailed description
以下将结合实施例对本发明做进一步说明，本发明的实施例仅用于说明本发明的技术方案，并非限定本发明。The present invention will be further described below in conjunction with the examples, and the examples of the present invention are only used to illustrate the technical solution of the present invention, not to limit the present invention.
实施例1Example 1
取硝基苯乙烯(0.2mmol,29.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌4h，反应进程去TLC检测。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)。产物通过1HNMR和HPLC分析，收率87％。Take nitrostyrene (0.2mmol, 29.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg), water (1mL), Magnetic stirring was carried out at room temperature for 4 h, and the reaction progress was detected by TLC. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1). The product was analyzed by 1 HNMR and HPLC, and the yield was 87%.
(R)-2,2-Dimethyl-4-nitro-3-phenylbutanal：TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat210nm(hexane/i-PrOH＝80:20,flowrate0.5mL/min,20℃).tR(major)＝31.8min,tR(minor)＝38.5min,ee＝97％.1HNMR(400MHz,CDCl3):δ9.55(s,1H),7.31-7.37(m,3H),7.21-7.23(m,2H),4.85-4.91(m,1H),4.69-4.74(m,1H),3.79-3.83(m,1H),1.15(s,3H),1.02(s,3H).(R)-2,2-Dimethyl-4-nitro-3-phenylbutanal: Theee was determined by HPLC with ChiralpakOD-Hcolumnat210nm (hexane/i-PrOH＝80:20, flowrate0.5mL/min, 20℃).t R (major)＝31.8min , t R (minor) = 38.5min, ee = 97%. 1 HNMR (400MHz, CDCl 3 ): δ9.55(s, 1H), 7.31-7.37(m, 3H), 7.21-7.23(m, 2H) ,4.85-4.91(m,1H),4.69-4.74(m,1H),3.79-3.83(m,1H),1.15(s,3H),1.02(s,3H).
实施例2Example 2
取硝基苯乙烯(0.2mmol,29.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，23mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌7h，反应进程去TLC检测。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)。产物通过1HNMR和HPLC分析，收率83％，ee＝97％。Take nitrostyrene (0.2mmol, 29.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 23mg), DMAP (0.04mmol, 4.9mg), water (1mL), Magnetic stirring was carried out at room temperature for 7 h, and the reaction progress was detected by TLC. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1). The product was analyzed by 1 HNMR and HPLC, the yield was 83%, ee=97%.
实施例3Example 3
取硝基苯乙烯(0.2mmol,29.8mg)，异丁醛(2mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌4h，反应进程去TLC检测。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)。产物通过1HNMR和HPLC分析，收率86％,ee＝98％。Take nitrostyrene (0.2mmol, 29.8mg), isobutyraldehyde (2mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg), water (1mL), Magnetic stirring was carried out at room temperature for 4 h, and the reaction progress was detected by TLC. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1). The product was analyzed by 1 HNMR and HPLC, the yield was 86%, ee=98%.
实施例4Example 4
取4-硝基-β-硝基苯乙烯(0.2mmol,38.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌4h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)，收率91％。Take 4-nitro-β-nitrostyrene (0.2mmol, 38.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg ), water (1 mL), and magnetically stirred at room temperature for 4 h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1), and the yield was 91%.
(R)-2,2-dimethyl-4-nitro-3-(4-nitrophenyl)butanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat208nm(hexane/i-PrOH＝75:25,flowrate0.5mL/min,20℃).tR(major)＝10.6min,tR(minor)＝11.6min,ee＝99％.1HNMR(400MHz,CDCl3):δ9.51(s,1H),8.22(d,2H,J＝8.8Hz),7.45(d,2H,J＝8.8Hz),4.91-4.97(m,1H),4.77-4.82(m,1H),3.93-3.97(m,1H),1.18(s,3H),1.07(s,3H).(R)-2,2-dimethyl-4-nitro-3-(4-nitrophenyl)butanal:Theee was determined by HPLCwithChiralpakOD-Hcolumnat208nm(hexane/i-PrOH=75:25, flowrate0.5mL/min, 20°C).t R ( major)＝10.6min, t R (minor)＝11.6min, ee＝99％. 1 HNMR (400MHz, CDCl 3 ): δ9.51(s, 1H), 8.22(d, 2H, J＝8.8Hz), 7.45(d,2H,J＝8.8Hz),4.91-4.97(m,1H),4.77-4.82(m,1H),3.93-3.97(m,1H),1.18(s,3H),1.07(s, 3H).
实施例5Example 5
取3-硝基-β-硝基苯乙烯(0.2mmol,38.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌器3h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)，收率92％。Take 3-nitro-β-nitrostyrene (0.2mmol, 38.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg ), water (1 mL), and a magnetic stirrer at room temperature for 3 h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1), and the yield was 92%.
(R)-2,2-dimethyl-4-nitro-3-(3-nitrophenyl)butanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝30.5min,tR(minor)＝31.7min,ee＝99.8％.1HNMR(400MHz,CDCl3):δ9.52(s,1H),8.22(t,1H),8.15(t,1H),7.55-7.62(m,2H),4.92-4.98(m,1H),4.78-4.82(m,1H),3.95-3.98(m,1H),1.10(s,3H),1.08(s,3H).(R)-2,2-dimethyl-4-nitro-3-(3-nitrophenyl)butanal:Theee was determined by HPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10, flowrate0.2mL/min, 20℃).t R ( major) = 30.5min, t R (minor) = 31.7min, ee = 99.8%. 1 HNMR (400MHz, CDCl 3 ): δ9.52(s, 1H), 8.22(t, 1H), 8.15(t, 1H ),7.55-7.62(m,2H),4.92-4.98(m,1H),4.78-4.82(m,1H),3.95-3.98(m,1H),1.10(s,3H),1.08(s,3H ).
实施例6Example 6
(R)-2,2-二甲基-4-硝基-3-(2-氯苯基)丁醛的制备：取2-氯-β-硝基苯乙烯(0.2mmol,36.7mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌5h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝10:1)，收率89％。Preparation of (R)-2,2-dimethyl-4-nitro-3-(2-chlorophenyl)butyraldehyde: Take 2-chloro-β-nitrostyrene (0.2mmol, 36.7mg), Isobutyraldehyde (1mmol, 0.91mL) was added to a 5mL flask, catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg), water (1mL), and magnetically stirred at room temperature for 5h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 10:1), and the yield was 89%.
(R)-2,2-dimethyl-4-nitro-3-(2-chlorophenyl)butanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝19.3min,tR(minor)＝20.8min,ee＝97％.1HNMR(400MHz,CDCl3):δ9.57(s,1H),7.44(d,1H,J＝7.6Hz),7.27-7.31(m,2H),7.23-7.26(m,1H),4.86(t,1H),4.72-4.83(m,1H),4.63-4.67(m,1H),1.18(s,3H),1.09(s,3H).(R)-2,2-dimethyl-4-nitro-3-(2-chlorophenyl)butanal:Theee was determined by HPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10, flowrate0.2mL/min, 20℃).t R ( major)=19.3min, t R (minor)=20.8min, ee=97%. 1 HNMR (400MHz, CDCl 3 ): δ9.57(s, 1H), 7.44(d, 1H, J=7.6Hz), 7.27-7.31(m,2H),7.23-7.26(m,1H),4.86(t,1H),4.72-4.83(m,1H),4.63-4.67(m,1H),1.18(s,3H), 1.09(s,3H).
实施例7Example 7
取4-甲氧基-β-硝基苯乙烯(0.2mmol,35.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌4h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝10:1)，收率81％。Take 4-methoxy-β-nitrostyrene (0.2mmol, 35.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9 mg), water (1mL), magnetically stirred at room temperature for 4h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 10:1), and the yield was 81%.
(R)-3-(4-methoxyphenyl)-2,2-dimethyl-4-nitrobutanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat210nm(hexane/i-PrOH＝75:25,flowrate0.5mL/min,20℃).tR(major)＝13.2min,tR(minor)＝14.9min,ee＝97％.1HNMR(400MHz,CDCl3):δ9.54(s,1H),7.13(d,2H,J＝8.4Hz),6.87(d,2H,J＝8.4Hz),4.79-4.85(m,1H),4.66-4.70(m,1H),3.80(s,3H),3.73-3.77(m,1H),1.14(s,3H),1.02(s,3H).(R)-3-(4-methoxyphenyl)-2,2-dimethyl-4-nitrobutanal: Theee was determined by HPLCwithChiralpakOD-Hcolumnat210nm(hexane/i-PrOH＝75:25, flowrate0.5mL/min, 20℃).t R (major )=13.2min, t R (minor)=14.9min, ee=97%. 1 HNMR (400MHz, CDCl 3 ): δ9.54(s, 1H), 7.13(d, 2H, J=8.4Hz), 6.87 (d,2H,J=8.4Hz),4.79-4.85(m,1H),4.66-4.70(m,1H),3.80(s,3H),3.73-3.77(m,1H),1.14(s,3H ),1.02(s,3H).
实施例8Example 8
取4-羟基-β-硝基苯乙烯(0.2mmol,33.0mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌3h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)，收率85％。Take 4-hydroxy-β-nitrostyrene (0.2mmol, 33.0mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg) , water (1 mL), and magnetically stirred at room temperature for 3 h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1), and the yield was 85%.
(R)-3-(4-hydroxyphenyl)-2,2-dimethyl-4-nitrobutanal:(Table8,entry7).TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝50.1min,tR(minor)＝56.7min,ee＝95％.1HNMR(400MHz,CDCl3):δ9.51(s,1H),7.04(d,2H,J＝7.6Hz),6.54(s,1H),4.82(t,1H),4.65-4.69(m,1H),3.71-3.75(m,1H),1.11(s,3H),0.99(s,3H).(R)-3-(4-hydroxyphenyl)-2,2-dimethyl-4-nitrobutanal: (Table8, entry7). Theee was determined by HPLC with ChiralpakOD-Hcolumnat254nm (hexane/i-PrOH＝90:10, flowrate0.2mL/min, 20℃ ).t R (major) = 50.1min, t R (minor) = 56.7min, ee = 95%. 1 HNMR (400MHz, CDCl 3 ): δ9.51(s, 1H), 7.04(d, 2H, J =7.6Hz),6.54(s,1H),4.82(t,1H),4.65-4.69(m,1H),3.71-3.75(m,1H),1.11(s,3H),0.99(s,3H) .
实施例9Example 9
取3,4-二甲氧基-β-硝基苯乙烯(0.2mmol,41.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌5h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝3:1)，收率83％。Take 3,4-dimethoxy-β-nitrostyrene (0.2mmol, 41.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04 mmol, 4.9mg), water (1mL), magnetically stirred at room temperature for 5h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 3:1), and the yield was 83%.
(R)-3-(3,4-dimethoxyphenyl)-2,2-dimethyl-4-nitrobutanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝34.2min,tR(minor)＝36.0min,ee＝96％.1HNMR(400MHz,CDCl3):δ9.54(s,1H),6.83(d,1H,J＝8.4Hz),6.75-6.78(m,1H),6.69(s,1H),4.82-4.88(m,1H),4.67-4.71(m,1H),3.89(s,3H),3.88(s,3H),3.71-3.75(m,1H),1.16(s,3H),1.05(s,3H).(R)-3-(3,4-dimethoxyphenyl)-2,2-dimethyl-4-nitrobutanal: Theee was determined by HPLC with ChiralpakOD-Hcolumnat254nm (hexane/i-PrOH＝90:10, flowrate0.2mL/min, 20℃).t R (major)=34.2min, t R (minor)=36.0min, ee=96%. 1 HNMR (400MHz, CDCl 3 ): δ9.54(s, 1H), 6.83(d, 1H, J=8.4Hz) ,6.75-6.78(m,1H),6.69(s,1H),4.82-4.88(m,1H),4.67-4.71(m,1H),3.89(s,3H),3.88(s,3H),3.71 -3.75(m,1H),1.16(s,3H),1.05(s,3H).
实施例10Example 10
取1-(2-硝基乙烯基)萘(0.2mmol,39.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌6h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)，收率84％。Take 1-(2-nitrovinyl)naphthalene (0.2mmol, 39.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg ), water (1 mL), and magnetically stirred at room temperature for 6 h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1), and the yield was 84%.
(R)-2,2-dimethyl-3-(naphthalen-1-yl)-4-nitrobutanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝31.6min,tR(minor)＝35.5min,ee＝96％.1HNMR(400MHz,CDCl3):δ9.61(s,1H),8.25(d,1H,J＝8.8Hz),8.88(d,1H,J＝7.6Hz),7.83(d,1H,J＝8.0Hz),7.61-7.63(m,1H),7.43-7.59(m,3H),4.96-5.05(m,2H),4.87-4.90(m,1H),1.23(s,3H),0.98(s,3H).(R)-2,2-dimethyl-3-(naphthalen-1-yl)-4-nitrobutanal: Theee was determined by HPLC with ChiralpakOD-Hcolumnat254nm (hexane/i-PrOH＝90:10, flowrate0.2mL/min, 20℃).t R (major)＝31.6min, t R (minor)＝35.5min, ee＝96％. 1 HNMR (400MHz, CDCl 3 ): δ9.61(s, 1H), 8.25(d, 1H, J＝8.8Hz) ,8.88(d,1H,J=7.6Hz),7.83(d,1H,J=8.0Hz),7.61-7.63(m,1H),7.43-7.59(m,3H),4.96-5.05(m,2H ),4.87-4.90(m,1H),1.23(s,3H),0.98(s,3H).
实施例11Example 11
取2-硝基噻吩乙烯(0.2mmol,31.0mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌5h。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝10:1)，收率86％。Take 2-nitrothiopheneethylene (0.2mmol, 31.0mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg), water (1mL ), magnetic stirring at room temperature for 5 h. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 10:1), and the yield was 86%.
(R)-2,2-dimethyl-4-nitro-3-(thiophen-2-yl)butanal:TheeewasdeterminedbyHPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).tR(major)＝36.7min,tR(minor)＝40.7min,ee＝99.6％.1HNMR(400MHz,CDCl3):δ9.56(s,1H),7.27(d,1H,J＝4.8Hz),6.94-6.99(m,2H),4.66-4.78(m,2H),4.14-4.18(m,1H),1.23(s,3H),1.10(s,3H).(R)-2,2-dimethyl-4-nitro-3-(thiophen-2-yl)butanal:Theee was determined by HPLCwithChiralpakOD-Hcolumnat254nm(hexane/i-PrOH＝90:10,flowrate0.2mL/min,20℃).t R (major)＝36.7min, t R (minor)＝40.7min, ee＝99.6％. 1 HNMR (400MHz, CDCl 3 ): δ9.56(s, 1H), 7.27(d, 1H, J＝4.8Hz ),6.94-6.99(m,2H),4.66-4.78(m,2H),4.14-4.18(m,1H),1.23(s,3H),1.10(s,3H).
实施例12Example 12
取硝基苯乙烯(0.2mmol,29.8mg)，异丁醛(1mmol,0.91mL)于5mL烧瓶中，加入催化剂(0.03mmol，34mg)，DMAP(0.04mmol，4.9mg)，水(1mL)，常温下磁力搅拌4h，反应进程去TLC检测。反应完后，用乙酸乙酯萃取数次，合并有机相，湿法过柱(洗脱剂：石油醚：乙酸乙酯＝5:1)。产物通过1HNMR和HPLC分析，收率87％。Take nitrostyrene (0.2mmol, 29.8mg), isobutyraldehyde (1mmol, 0.91mL) in a 5mL flask, add catalyst (0.03mmol, 34mg), DMAP (0.04mmol, 4.9mg), water (1mL), Magnetic stirring was carried out at room temperature for 4 h, and the reaction progress was detected by TLC. After the reaction, it was extracted several times with ethyl acetate, the organic phases were combined, and passed through the column by wet method (eluent: petroleum ether: ethyl acetate = 5:1). The product was analyzed by 1 HNMR and HPLC, and the yield was 87%.
离子液体重复使用5次，未发现收率明显下降，具体见表1.NMR数据实施例1。The ionic liquid was reused 5 times, and no obvious decrease in the yield was found, see Table 1. NMR data Example 1 for details.
表1Table 1
需要说明的是，上述发明内容及具体实施方式意在证明本发明所提供技术方案的实际应用，不应解释为对本发明保护范围的限定。本领域技术人员在本发明的精神和原理内，当可作各种修改、等同替换、或改进。本发明的保护范围以所附权利要求书为准。It should be noted that the above summary of the invention and specific implementation methods are intended to demonstrate the practical application of the technical solution provided by the present invention, and should not be construed as limiting the protection scope of the present invention. Those skilled in the art may make various modifications, equivalent replacements, or improvements within the spirit and principles of the present invention. The protection scope of the present invention shall be determined by the appended claims.
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