CN102180828A - Chiral indolinone spiropentacyclic skeleton compounds and asymmetric synthesis thereof - Google Patents
Chiral indolinone spiropentacyclic skeleton compounds and asymmetric synthesis thereof Download PDFInfo
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- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 150000001875 compounds Chemical class 0.000 title claims abstract description 17
- 238000011914 asymmetric synthesis Methods 0.000 title abstract description 3
- 238000006352 cycloaddition reaction Methods 0.000 claims abstract description 15
- 238000005712 Baylis-Hillman reaction Methods 0.000 claims abstract description 14
- 125000000524 functional group Chemical group 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 10
- -1 butyne diester Chemical class 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- RJAQXMAQJDHOSH-UHFFFAOYSA-N 3-prop-2-ynylsulfonylprop-1-yne Chemical compound C#CCS(=O)(=O)CC#C RJAQXMAQJDHOSH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000654 additive Substances 0.000 claims abstract 2
- 239000002808 molecular sieve Substances 0.000 claims abstract 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 10
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 9
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 9
- 229960000948 quinine Drugs 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 150000003949 imides Chemical class 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 150000005690 diesters Chemical class 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims description 2
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims description 2
- FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 229930014626 natural product Natural products 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 abstract 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract 1
- 235000021513 Cinchona Nutrition 0.000 abstract 1
- 241000157855 Cinchona Species 0.000 abstract 1
- 150000001335 aliphatic alkanes Chemical class 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- KDKYADYSIPSCCQ-UHFFFAOYSA-N ethyl acetylene Natural products CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 abstract 1
- 230000001766 physiological effect Effects 0.000 abstract 1
- 125000003367 polycyclic group Chemical group 0.000 abstract 1
- 229960002317 succinimide Drugs 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- ULTQUFCPWDEOND-FOLHBFKUSA-N β-isocupreidine Chemical compound C1=C(O)C=C2C([C@H]3C4CC5CCN4C[C@@]5(O3)CC)=CC=NC2=C1 ULTQUFCPWDEOND-FOLHBFKUSA-N 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 238000001819 mass spectrum Methods 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical group CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种高效合成含有手性吲哚啉酮螺五环骨架化合物的方法。该方法是一种有效的以手性胺，特别是金鸡纳碱衍生的beta-ICD((3S,8R,9S)-10,11-二氢-3，9环氧-6'–羟基金鸡纳烷)的衍生物作为催化剂，以4Å分子筛作为添加剂，由吲哚啉酮MBH(Morita-Baylis-Hillman)碳酸酯和各类亲偶极体化合物（如，炔丙基砜，丁炔二酯，丁二酰亚胺等等）高效率、高对映选择性的合成一系列具有多功能官能团的形式3+2环加成手性产物的方法。该不对称合成方法为首次报道，不仅催化剂易得，催化活性高，反应条件温和，操作简单，底物适用范围广，产物区域和对映选择性高，而且得到的各类含有吲哚啉酮螺环或多环骨架可能具有特殊生理活性或成为天然产物的重要合成中间体。The invention provides a method for efficiently synthesizing compounds containing chiral indolinone spiro pentacyclic skeleton. This method is an efficient method for beta-ICD ((3S,8R,9S)-10,11-dihydro-3,9epoxy-6'-hydroxycinchona) derived from chiral amines, especially cinchona base Alkanes) derivatives as catalysts, with 4Å molecular sieves as additives, by indolinone MBH (Morita-Baylis-Hillman) carbonate and various dipolar-philic compounds (such as, propargyl sulfone, butyne diester, succinimide, etc.) high-efficiency, high-enantioselective synthesis of a series of 3+2 cycloaddition chiral products with multifunctional functional groups. This asymmetric synthesis method is reported for the first time, not only the catalyst is easy to obtain, the catalytic activity is high, the reaction conditions are mild, the operation is simple, the substrate is applicable to a wide range, the product regio and enantioselectivity are high, and all kinds of indolinones containing Spiral or polycyclic skeletons may have special physiological activities or become important synthetic intermediates of natural products.
Description
Technical field
The present invention relates to a kind ofly have the cycloaddition product of multi-functional functional group spiral shell Pentacyclic indole quinoline ketone by the synthetic class of Chiral Amine catalyzing indole quinoline ketone MBH (Morita-Baylis-Hillman) carbonic ether and all kinds of dipolarophile body compound, it is active or become the important synthetic intermediate of natural product that this multi-functional functional group product may have special physiological.
Background technology
Volution indolinone skeleton, especially optically pure this class skeleton extensively is present in natural product and the pharmaceutical intermediate.In view of this compounds pharmaceutically vital role, caused increasing chemist's interest.[(a) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003,2209. (b) Trost, B. M.; Brennan, M. K. Synthesis 2009,3003. (c) Zhou, F.; Liu, Y.; Zhou, J. Adv. Synth. Catal. 2010,352,1381.] wherein adopt the cycloaddition method to construct the volution skeleton to have obtained great development [(a) Corey, E. J. Angew. Chem., Int. Ed. 2002 especially in recent years, 41,1650. (b) Sebahar, P. R.; Williams, R. M. J. Am. Chem. Soc. 2000,122,5666. (c) Trost, B. M.; Cramer, N.; Silverman, S. M. J. Am. Chem. Soc. 2007,129,12396. (d) Bencivenni, G.; Wu, L.; Mazzanti, A.; Giannichi, B.; Pesciaioli, F.; Song, M.; Bartoli, G.; Melchiorre, P. Angew. Chem., Int. Ed. 2009,48,7200. (e) Chen, X.; Wei, Q.; Luo, S.; Xiao, H.; Gong, L. J. Am. Chem. Soc. 2009,131,13819. (f) Wei, Q.; Gong, L. Org. Lett. 2010,12,1008] simultaneously, in this field, we have also developed with chirality Prolinol silicon ether and have constructed volution indolinone structure product [(a) Jiang, K. as a series of cascade reactions of catalyst; Jia, Z-J.; Chen, S.; Wu, L.; Chen, Y-C. Chem. Eur. J. 2010,16,2852. (b) Jiang, K.; Jia, Z-J.; Yin, X.; Wu, L.; Chen, Y-C. Org. Lett. 2010,12,2766.] and chirality quinine deutero-tertiary amine as the indolinone C-3 position electrophilic addition of catalyst after the intramolecularly Michael reaction construct spirane structure [Peng, J.; Huang, X.; Cui, H-L.; Chen, Y-C. Org. Lett. 2010,12,4260.].But up till now for this reason, can be effectively in the document to obtain the asymmetric reaction of optical purity indolone volution amylene by cycloaddition reaction considerably less.Therefore, develop a kind of easy and simple to handle, environmental friendliness, and high enantioselectivity synthetic a kind of has the cycloaddition product of multi-functional functional group and then makes up a series of methods that contain indolinone volution skeleton and have an active compound of potential drug and have great significance.
Summary of the invention
The purpose of this invention is to provide a kind of cycloaddition product that contains multi-functional functional group.
Purpose of the present invention or a kind of synthetic method that contains the cycloaddition product of multi-functional functional group is provided.
The cycloaddition product of multi-functional functional group of the present invention, it is just like graph structure:
, wherein * is a chiral carbon atom, PG is selected from Ac, Boc, Bz, Cbz, Me or H arbitrarily; R
1Be selected from alkyl, aryl arbitrarily; The indolinone aryl
Replace wherein R
2, R
3, R
4Or R
5Be selected from the-oxyl of H, F, Cl, Br, C1-C16 arbitrarily, the alkyl of C1-C16; EWG is selected from the benzene sulfuryl arbitrarily, heterocycle sulfuryl and various carbonyl (ester, ketone, imide etc.); On behalf of ethanoyl, Boc, wherein said Ac represent tertbutyloxycarbonyl, Bz to represent benzoyl, Cbz to represent carbobenzoxy-(Cbz), Me represent methylidene.
The cycloaddition product of multi-functional functional group of the present invention is to be raw material with indolinone MBH carbonic ether and all kinds of dipolarophile body compound, in the presence of organic solvent, quinine deutero-beta-ICD derivative with chirality makes as catalyst reaction, and available following reaction formula is represented:
Further describing of this reaction is 25 at the organic solvent neutral temperature
oC, with indolinone MBH carbonic ether and all kinds of dipolarophile body compound (as, propargyl sulfone, butine diester, succimide or the like) be raw material, with the derivative of the quinine deutero-beta-ICD of chirality as catalyst reaction 12 hours to 24 hours; The mol ratio of the quinine deutero-beta-ICD derivative of wherein said indolinone MBH carbonic ether, all kinds of dipolarophile body compound and chirality is 1 ~ 2:1:0.05 ~ 0.1.
The structural formula of indolinone MBH carbonic ether is:
, wherein: PG is selected from Ac, Boc, Bz, Cbz, Me or H arbitrarily; The indolinone aryl
Replace wherein R
2, R
3, R
4Or R
5Be selected from the-oxyl of H, F, Cl, Br, C1-C16 arbitrarily, the alkyl of C1-C16; The structural formula of all kinds of dipolarophile body compounds is:
, wherein: R
1Be selected from alkyl, aryl arbitrarily; EWG is selected from the benzene sulfuryl arbitrarily, heterocycle sulfuryl and various carbonyl (ester, ketone, imide etc.).
The general structure of catalyzer is (be any optically pure structure, not limit by diagram):
, wherein R is selected from H arbitrarily; CH
3O, BnO, CH
3OCH
2O, BnOCH
2Various alkoxyl groups such as O; Various substituted aryls or heterocyclic base; Various ester groups are as the trifluoro sulphonate; Various secondary amine or nitrogen heterocyclic ring are as morpholine, piperidines etc.
The alkyl that the present invention mentioned,-oxyls etc. unless otherwise indicated, all are recommended as carbon number and are 1 ~ 16 group, and further recommending carbon number is 1 ~ 10 group, and especially recommending carbon number is 1 ~ 4 group.The aryl that the present invention mentioned unless otherwise indicated, all refers to phenyl or naphthyl, is recommended as phenyl.The heterocyclic base that the present invention mentioned unless otherwise indicated, all is recommended as the N that contains of C5 ~ C10, O, and the heterocyclic radical of S is especially recommended benzothiazolyl.The carbonyl that the present invention mentioned all is recommended as carbon number and is 1 ~ 16 group, and further recommending carbon number is 1 ~ 10 group; especially recommending carbon number is 1 ~ 4 group, unless otherwise indicated, and the equal nail ester group of ester group; ketone all refers to benzoyl, and imide all refers to N-phenyl butylene imide.
Organic solvent of the present invention can be polar solvent or non-polar solvent, as: methylene dichloride, chloroform, tetracol phenixin, 1,2-ethylene dichloride, toluene, m-xylene, sym-trimethylbenzene, phenylfluoroform, 1,4-dioxane, tetrahydrofuran (THF) etc.
Adopt the prepared product of the present invention to be separated through the method for column chromatography.Used developping agent and eluent are the mixed solvent of polar solvent and non-polar solvent.Recommend solvent: sherwood oil-ethyl acetate.
The invention provides a kind of effectively with the quinine deutero-beta-ICD derivative of chirality as catalyzer, by indolinone MBH carbonic ether and all kinds of dipolarophile body compound (as, the propargyl sulfone, butine diester, succimide or the like) synthetic a kind of method of high-level efficiency, high enantioselectivity with cycloaddition product of multi-functional functional group spiral shell Pentacyclic indole quinoline ketone.This method not only catalyzer is easy to get, the catalytic activity height, and the reaction conditions gentleness, simple to operate, wide application range of substrates, also better (being generally 37%-94%) enantioselectivity height (being generally 76%-99%) of productive rate.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment: the indolinone MBH carbonic ether of chirality quinine deutero-beta-ICD derivatives catalysis and the cycloaddition reaction of all kinds of dipolarophile body compounds
In a clean reaction tubes, add chirality quinine deutero-beta-ICD derivative catalyst (0. 01mmol) successively, indolinone MBH carbonic ether (0.12mmol), dipolarophile body compound (0.1mmol), with m-xylene 0.1 mL, the corresponding time of stirring reaction under 25 ° of C.Column chromatography for separation gets product.
P10,81% yield; [α]
D 20=-54.0 (
c=0.3 in CHCl
3); 97% ee, the chirality test condition: determined by HPLC analysis [Daicel Chiralpak AD,
n-hexane/
i-PrOH=80/20,1.0 mL/min, λ=254 nm, t (major)=10.899 min, t (minor)=7.981 min];
1H NMR (400 MHz, CDCl
3): δ=7.96 (d,
J=7.6 Hz, 2H), 7.73-7.67 (m, 3H), 7.60 (t,
J=7.6 Hz, 2H), 7.49 (s, 1H), 6.94 (s, 1H), 3.62 (s, 3H), 2.07 (s, 3H), 1.61 (s, 9H) ppm;
13C NMR (100 MHz, CDCl
3): δ=167.7,161.2,160.4,148.4,142.1,142.0,140.4,140.0,138.6,134.2,130.4,130.0,129.7,127.3,124.4,122.6,117.4,85.6,74.0,52.1,28.0,12.3 ppm; High resolution mass spectrum calculating value: (C
26H
24ClNO
7S+Na) m/z 552.0860, measured value: 552.0864.
P16,88% yield; [α]
D 20=-16.6 (
c=0.9 in CHCl
3); 93% ee, the chirality test condition: determined by HPLC analysis [Daicel Chiralcel OD,
n-hexane/
i-PrOH=80/20,1.0 mL/min, λ=254 nm, t (major)=6.220 min, t (minor)=13.943 min];
1H NMR (400 MHz, CDCl
3): δ=7.96 (d,
J=8.0 Hz, 1H), 7.52 (s, 1H), 7.35 (td,
J=8.0 Hz, 0.8 Hz, 1H), 7.05 (td,
J=8.0 Hz, 0.8 Hz, 1H), 6.79 (d,
J=7.6 Hz, 1H), 3.91 (s, 3H), 3.64 (s, 3H), 3.60 (s, 3H), 1.65 (s, 9H) ppm;
13C NMR (100 MHz, CDCl
3): δ=175.5,174.8,173.2,172.1,161.7,140.5,140.2,139.5,130.1,129.2,128.9,125.9,124.4,123.0,115.8,84.9,52.9,52.7,52.4,28.1 ppm; High resolution mass spectrum calculating value: (C
23H
23NO
9+ Na) m/z 480.1271, measured value: 480.1274.
Claims (4)
1. a class contains the cycloaddition product of multi-functional functional group volution indolinone, and it is the optical pure compound with following structure:
, wherein * is a chiral carbon atom, PG is selected from Ac, Boc, Bz, Cbz, Me or H arbitrarily; R
1Be selected from alkyl, aryl arbitrarily; The indolinone aryl replaces
R wherein
2, R
3, R
4Or R
5Be selected from the-oxyl of H, F, Cl, Br, C1-C16 arbitrarily, the alkyl of C1-C16; EWG is selected from the benzene sulfuryl arbitrarily, heterocycle sulfuryl and various carbonyl (ester, ketone, imide etc.).
2. on behalf of ethanoyl, Boc, wherein said Ac represent tertbutyloxycarbonyl, Bz to represent benzoyl, Cbz to represent carbobenzoxy-(Cbz), Me represent methylidene.
3. synthetic method by the cycloaddition product of the described multi-functional functional group of claim 1 volution indolinone, it is characterized in that under-10 ~ 50 degrees centigrade condition in organic solvent, with indolinone Morita-Baylis-Hillman (MBH) carbonic ether and all kinds of dipolarophile body compound (as, the propargyl sulfone, the butine diester, succimide or the like) is raw material, with 4 molecular sieves as additive, with Chiral Amine, the derivative of quinine deutero-beta-ICD particularly, the indolone cycloaddition reaction of carrying out as catalyzer, wherein indolinone MBH carbonic ether, the mol ratio of the derivative of dienophile compound and quinine deutero-beta-ICD is 1 ~ 2:1:0.05 ~ 0.1; The structure of the quinine deutero-beta-ICD derivative catalyst of wherein said chirality is:
Wherein R is selected from H, CH arbitrarily
3O, BnO, CH
3OCH
2O, BnOCH
2Various alkoxyl groups such as O; Various substituted aryls or heterocyclic base; Various ester groups are as the trifluoro sulphonate; Various secondary amine or nitrogen heterocyclic ring are as morpholine, piperidines etc.
4. the method for the cycloaddition product of synthetic multi-functional functional group according to claim 2 volution indolinone, it is characterized in that described solvent is arranged is methylene dichloride, chloroform, tetracol phenixin, 1,2-ethylene dichloride, toluene, m-xylene, sym-trimethylbenzene, phenylfluoroform, 1,4-dioxane, tetrahydrofuran (THF).
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| CN102584800A (en) * | 2011-12-16 | 2012-07-18 | 四川大学 | Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method |
| CN104086477A (en) * | 2014-07-15 | 2014-10-08 | 西华师范大学 | Preparation method of optical-activity spiropentyl-1,3'-indole and derivatives thereof |
| CN104860939A (en) * | 2015-04-10 | 2015-08-26 | 昆明理工大学 | Cinchona alkaloids compound and preparation method thereof |
| CN107226816A (en) * | 2017-05-27 | 2017-10-03 | 重庆文理学院 | A kind of preparation method of indoline spiro-compound |
| CN113149890A (en) * | 2021-04-27 | 2021-07-23 | 华东理工大学 | Method for synthesizing 3-spiro-2-indolone compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102584800A (en) * | 2011-12-16 | 2012-07-18 | 四川大学 | Compound containing framework of chiral indolone and angelica lactone and asymmetric synthesis method |
| CN104086477A (en) * | 2014-07-15 | 2014-10-08 | 西华师范大学 | Preparation method of optical-activity spiropentyl-1,3'-indole and derivatives thereof |
| CN104086477B (en) * | 2014-07-15 | 2017-04-12 | 西华师范大学 | Preparation method of optical-activity spiropentyl-1,3'-indole and derivatives thereof |
| CN104860939A (en) * | 2015-04-10 | 2015-08-26 | 昆明理工大学 | Cinchona alkaloids compound and preparation method thereof |
| CN107226816A (en) * | 2017-05-27 | 2017-10-03 | 重庆文理学院 | A kind of preparation method of indoline spiro-compound |
| CN113149890A (en) * | 2021-04-27 | 2021-07-23 | 华东理工大学 | Method for synthesizing 3-spiro-2-indolone compounds |
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