CN113372324A - Method for synthesizing spiro compound through lithium iodide catalysis - Google Patents
Method for synthesizing spiro compound through lithium iodide catalysis Download PDFInfo
- Publication number
- CN113372324A CN113372324A CN202110680838.XA CN202110680838A CN113372324A CN 113372324 A CN113372324 A CN 113372324A CN 202110680838 A CN202110680838 A CN 202110680838A CN 113372324 A CN113372324 A CN 113372324A
- Authority
- CN
- China
- Prior art keywords
- spiro
- lithium iodide
- solvent
- reaction
- catalytic synthesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 title claims abstract description 62
- 150000003413 spiro compounds Chemical class 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 21
- NSDWWGAIPUNJAX-UHFFFAOYSA-N o-quinomethane Chemical compound C=C1C=CC=CC1=O NSDWWGAIPUNJAX-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 19
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 7
- 229920002554 vinyl polymer Polymers 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 69
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- -1 2, 4-dimethoxyphenyl Chemical group 0.000 claims description 19
- 239000003208 petroleum Substances 0.000 claims description 11
- 239000012043 crude product Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000012046 mixed 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
- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 229940007550 benzyl acetate Drugs 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 238000007036 catalytic synthesis reaction Methods 0.000 claims 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000003003 spiro group Chemical group 0.000 abstract description 10
- 230000004913 activation Effects 0.000 abstract description 9
- YIWFBNMYFYINAD-UHFFFAOYSA-N ethenylcyclopropane Chemical compound C=CC1CC1 YIWFBNMYFYINAD-UHFFFAOYSA-N 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 7
- SQZFVNSRRPRBQP-UHFFFAOYSA-N ethenylcyclobutane Chemical compound C=CC1CCC1 SQZFVNSRRPRBQP-UHFFFAOYSA-N 0.000 abstract description 5
- UFQGSPKFLBLFAY-UHFFFAOYSA-N cyclohexane cyclopentane Chemical compound C1CCCCC1.C1CCCCC1.C1CCCC1 UFQGSPKFLBLFAY-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 125000005605 benzo group Chemical group 0.000 description 20
- GYRVFISXYPPJBT-UHFFFAOYSA-N 1,3-dioxan-5-one Chemical compound O=C1COCOC1 GYRVFISXYPPJBT-UHFFFAOYSA-N 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 5
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- XJDDLMJULQGRLU-UHFFFAOYSA-N 1,3-dioxane-4,6-dione Chemical compound O=C1CC(=O)OCO1 XJDDLMJULQGRLU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011877 intramolecular nucleophilic addition Methods 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention provides a method for synthesizing a spiro compound by lithium iodide catalysis, which comprises the following steps: in a solvent, under the catalysis of lithium iodide, the o-quinone methide I and the vinyl cyclane compound II undergo a cyclization reaction to obtain a spiro compound III. The method of the invention activates a new activation mode of vinylcyclopropane or vinylcyclobutane through lithium iodide, so that the vinylcyclopropane or vinylcyclobutane and cheap and easily-obtained o-quinone methide are subjected to cyclization reaction to synthesize spiro [ cyclohexane-cyclopentane]And spiro [ cyclohexane-cyclohexane]The spiro compounds have the advantages of simple catalytic system, high efficiency, convenient operation, wide substrate application range, cheap and easily obtained reaction raw materials and catalysts, and the like.
Description
Technical Field
The invention relates to a method for synthesizing a spiro compound by catalyzing lithium iodide, belonging to the technical field of organic synthesis.
Background
Spiro structures such as spiro [ cyclohexane-cyclopentane ] and spiro [ cyclohexane-cyclohexane ] are widely present in natural products and bioactive molecules, and compared with planar aromatic structures, three-dimensional spiro compounds exhibit certain rigidity and can stabilize the configuration of molecules, and at the same time, the three-dimensional spiro compounds are better flexible frameworks, which can affect the absorption, metabolism and other characteristics of the molecules (Chupakhin, e.; Babich, o.; Prosekov, a.; ayakia, l.; kravavin, m.telecules 2019,24, 4165); furthermore, the concept of more stable conformation of the molecule and better binding to the receptor molecule when the spiro structure contains adjacent quaternary carbon centers has been widely used in drug design (Zheng, y.; Tice, c.m.; Singh, s. b. bioorg. med. chem. lett.2014,24,3673.). Many methods for synthesizing cyclohexane spirocyclopentane and cyclohexane spirohexane compounds have been developed, such as intramolecular reactions, rearrangement reactions, intramolecular nucleophilic addition reactions, and intermolecular nucleophilic substitution reactions based on transition metal catalysis. However, these methods have problems such as severe reaction conditions, poor functional group tolerance, and complicated precursor preparation.
O-quinone methides were first discovered as a highly active intermediate in the biogenic synthesis of natural products, but they are difficult to separate due to their high activity, and thus chemists have mainly applied them as intermediates in chemical synthesis by in situ generation. In the current research, the quaternary ammonium salt is used as a quaternary synthon to carry out a series of [4+ n ] (n is more than or equal to 2) cycloaddition reactions. For example, the alpha, beta-unsaturated aldehyde can be subjected to [4+3] cyclization reaction under the action of an azacyclo-carbene catalyst (Lv, H.; Jia, W. -Q.; Sun, L. -H.; Ye, S.Angew.chem., int.Ed.2013,52, 8607-; in addition, cyclization reactions can also be carried out under Lewis acid and transition metal catalysis (Zhang, J.; Lin, L.; He, C.; Xiong, Q.; Liu, X.; Feng, X.Chem.Commun.2018,54, 74-77.). Therefore, the research on the participation of the o-quinone methide as a binary synthon in the cyclization reaction has important significance in expanding the diversity application of the cheap and easily available raw materials, but the difficulty that the o-quinone methide as a binary synthon in the cyclization reaction process has the difficulty that an aromatized intermediate formed after nucleophilic addition undergoes a ring closing process of dearomatization.
Vinylcyclopropane allows easy cleavage of carbon-carbon bonds due to the large ring tension, while the vinyl group as an activating group expands the activation mode of such cyclopropanes. Currently, for vinylcyclopropane, there are mainly the following types of activation: low valent transition metal activation (Cheng, Q.; Xie, J. -H.; Weng, Y. -C.; You, S. -L.Angew.chem., int. Ed.2019,58, 5739-; lewis acid activation (Mondal, B.; Das, D.; Saha, J.org.Lett.2020,22, 5115-; activation of Lewis bases (Zhang, J.; Tang, Y.; Wei, W.; Wu, Y.; Li, Y.; Zhang, J.; ZHEN, Y.; Xu, S. org. Lett.2017,19, 3043-). 3046.). However, it is still necessary to research a new activation mode of a vinylcyclopropane compound, improve the reaction catalytic efficiency, and develop a new reaction.
Therefore, the development of a new activation method of the vinylcyclopropane or vinylcyclobutane compound has important significance in enabling the vinylcyclopropane or vinylcyclobutane compound to react with the o-quinone methide to generate the spiro compound. The invention is therefore proposed.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for synthesizing a spiro compound by using lithium iodide as a catalyst. The method of the invention activates the new activation mode of the vinylcyclopropane or the vinylcyclobutane through lithium iodide, so that the vinylcyclopropane or the vinylcyclobutane and the cheap and easily obtained o-quinone methide are subjected to cyclization reaction to synthesize spiro compounds such as spiro [ cyclohexane-cyclopentane ] and spiro [ cyclohexane-cyclohexane ].
Description of terms:
room temperature: having a meaning well known in the art, meaning 25. + -. 5 ℃.
The technical scheme of the invention is as follows:
a method for synthesizing spiro compounds by catalysis of lithium iodide comprises the following steps:
in a solvent, under the catalysis of lithium iodide, carrying out cyclization reaction on an o-quinone methide I and a vinyl cycloparaffin compound II to obtain a spiro compound III;
wherein:
R1is phenyl, 4-methoxyphenyl, 3, 4-dimethoxyphenyl or 2, 4-dimethoxyphenyl;
R2is phenyl, benzyl, methyl, ethyl, isopropyl or tert-butyl;
R3is hydrogen, phenyl, 4-methoxyphenyl, 4-bromophenyl, benzyl, furyl, thienyl, methyl, ethyl or dimethyl;
R4is hydrogen, phenyl, methyl, ethyl or isopropyl;
n is 1 or 2.
According to the invention, the solvent is preferably dichloromethane, 1, 2-dichloroethane, 1, 4-dioxane, acetone, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, benzyl acetate, tert-butyl acetate, ethyl benzoate, toluene, ethylbenzene or chlorobenzene; further preferably, the solvent is acetonitrile, ethyl acetate or tetrahydrofuran; the solvent is subjected to anhydrous treatment.
According to the invention, the ratio of the volume of the solvent to the mole number of the o-quinone methide I is preferably 5-15mL:1 mmol.
According to the invention, the molar ratio of the lithium iodide to the o-quinone methide I is preferably 0.05-0.1: 1.
According to the invention, the mol ratio of the o-quinone methide I to the vinyl cyclane compound II is preferably 1-1.5: 1.
According to the invention, the temperature of the cyclization reaction is preferably 0-room temperature; the cyclization reaction time is 0.5-36h, and more preferably 8-18 h.
Preferably, according to the invention, the cyclization is carried out under a nitrogen atmosphere.
According to the invention, after the cyclization reaction of the o-quinone methide I and the vinyl cycloparaffin compound II, the product can be separated and characterized by a conventional separation and purification method. Preferably, the post-treatment steps of the reaction liquid obtained after the cyclization reaction of the o-quinone methide I and the vinyl naphthenic compound II are as follows: adding water into the reaction liquid for quenching reaction, then extracting with ethyl acetate, drying the obtained organic phase with anhydrous sodium sulfate, then removing the solvent to obtain a crude product, separating and purifying the obtained crude product by silica gel column chromatography to obtain the spiro compound III, wherein the eluent is a mixed solvent of ethyl acetate, dichloromethane and petroleum ether, and the volume ratio of the ethyl acetate, the dichloromethane and the petroleum ether in the mixed solvent is 0.05-0.25:0-0.2: 1.
According to the invention, R3In the case of dimethyl, the structure of the vinylcycloalkane compound II is shown as follows:
according to the invention, the o-quinone methide I is synthesized by the corresponding phenolic compound through the prior art (see the literature: An, X. -T.; Du, J. -Y.; Jia, Z. -L.; Zhang, Q.; Yu, K. -Y.; Zhang, Y. -Z.; Zhao, X. -H.; Fan, R.; Fan, C. -A.Chem.Eur.J.2020,26, 3803-:
in the above formula, the substituent R1As described above.
According to the invention, the vinylcycloalkane compound II, in which n is 1, is a vinylcyclopropan compound and is synthesized from the corresponding malonate by the prior art (see the literature: Matsumoto, Y.; Nakatake, D.; Yazaki, R.; Ohshima, T. chem. Eur. J.2018,24, 6062-:
in the above formula, the substituent R2、R3、R4As described above.
According to the invention, the vinylcycloalkane compound II, in which n is 2, is a vinylcyclobutane compound synthesized by the prior art from the corresponding methylidene malonate and an arylalkene (Luo, H.; Yan, J.; Chen, Z.; Wei, Y.; Chen, B.; Liu, Y. chemistry Select2020,5, 4074-one 4077.), according to the following reaction scheme:
in the above formula, the substituent R2、R3、R4As described above.
The invention has the following technical characteristics and beneficial effects:
1. the invention takes different o-quinone methide and vinyl cyclopropane or vinyl cyclobutane compounds as raw materials, and respectively generates [3+2] or [4+2] cyclization reaction under the catalysis of a simple, easily obtained and low-cost catalyst lithium iodide to generate spiro compounds such as spiro [ cyclohexane-cyclopentane ] and spiro [ cyclohexane-cyclohexane ]. The method has mild reaction conditions, and can synthesize the spiro compound with high efficiency.
2. According to the method, the used catalyst is lithium iodide with a simple structure and low price, and the method has the advantages of simple catalytic system and high efficiency; meanwhile, the method for constructing the spiro compound through the [3+2] or [4+2] cyclization reaction has the advantages of convenience in operation, wide substrate application range, cheap and easily available reaction raw materials and catalysts and the like.
Detailed Description
The present invention will be further described with reference to the following examples, but is not limited thereto.
Meanwhile, the experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents, materials and devices are commercially available, unless otherwise specified.
The yields described in the examples are molar yields.
Example 1
Synthesis of methyl 2' -p-methoxyphenyl-5 ' - (E) -styryl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (IIIa) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, to a 5mL flask were added in this order (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), methyl 2- (E) -styrylcyclopropanyl-1, 1-dicarboxylate (IIa) (26.0mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol), and then to the reaction system was added anhydrous acetonitrile (1.0mL) and the reaction was stirred at room temperature for 18 hours; after the reaction was completed, the reaction mixture was quenched with water (3mL), extracted with ethyl acetate (3 × 4mL), the organic phases were combined, dried over anhydrous sodium sulfate, and then the solvent was removed by rotary evaporation, and the obtained crude product was separated and purified by column chromatography (eluent was ethyl acetate: petroleum ether ═ 1:10-1:4, v/v) to give methyl 2' -p-methoxyphenyl-5 ' - (E) -styryl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (iiia) 42.4mg as a white solid in 82% yield.
The characterization data of the product (IIIa) obtained are as follows:
white solid (42.4mg, 82%);1H NMR(400MHz,CDCl3)δ7.27(d,J＝4.4Hz,4H),7.23–7.17 (m,1H),7.09(d,J＝8.8Hz,2H),6.71(d,J＝8.8Hz,2H),6.39(d,J＝15.8Hz,1H),6.35(s,1H), 5.97(dd,J＝15.8,8.1Hz,1H),5.68(d,J＝17.1Hz,2H),5.45(s,1H),4.77(s,1H),3.75(s,3H), 3.73(s,3H),3.42–3.32(m,4H),3.21(t,J＝13.8Hz,1H),2.56(dd,J＝14.2,7.2Hz,1H)。
13C NMR(100MHz,CDCl3)δ199.0,172.5,172.3,163.2,158.8,144.9,136.9,132.3,130.9, 128.5,127.7,127.4,126.8,126.3,113.0,104.0,101.2,99.8,65.9,62.9,62.5,55.0,54.3,53.0,52.6, 38.5。
HRMS(ESI):m/z calcd for C30H29O8:517.1857[M+H]+,found:517.1860。
example 2
Synthesis of methyl 2' -p-methoxyphenyl-5 ' - ((E) -2- (furan-2-yl) vinyl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxin-5, 1' -cyclopenta-ne) -3',3' -dicarboxylate (IIIb) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, to a 5mL flask were added (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), methyl 2- ((E) -2- (furan-2-yl) vinyl) cyclopropane-1, 1-dicarboxylate (IIb) (25.0mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol) in this order, and then to the reaction system was added anhydrous acetonitrile (1.0mL) and the reaction was stirred at room temperature for 12 hours; after the reaction was complete, it was quenched with water (3mL), extracted with ethyl acetate (3 × 4mL), the organic phases were combined, dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation, and the crude product obtained was purified by column chromatography (eluent ethyl acetate: dichloromethane: petroleum ether ═ 2:3:25, v/v/v) to give 35.5mg of methyl 2' -p-methoxyphenyl-5 ' - ((E) -2- (furan-2-yl) vinyl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxin-5, 1' -cyclopentane) -3',3' -dicarboxylate (iiib) as a white solid in 70% yield.
The characterization data of the product (IIIb) obtained are as follows:
white solid (35.5mg, 70% yield);1H NMR(400MHz,CDCl3)δ7.29(brs,1H),7.08(d,J＝8.8 Hz,2H),6.70(d,J＝8.7Hz,2H),6.32(brs,2H),6.19(d,J＝15.8Hz,1H),6.13(d,J＝3.2Hz,1H), 5.89(dd,J＝15.8,8.3Hz,1H),5.74(s,1H),5.68(s,1H),5.44(s,1H),4.73(s,1H),3.75(s,3H), 3.73(s,3H),3.39(s,3H),3.32(dd,J＝14.0,6.6Hz,1H),3.18(t,J＝13.8Hz,1H),2.53(dd,J＝ 14.2,7.1Hz,1H)。
13C NMR(100MHz,CDCl3)δ199.0,172.5,172.2,163.3,158.8,152.4,145.0,141.7,130.9, 127.6,125.4,120.7,113.0,111.2,107.8,103.9,101.3,99.8,65.9,62.8,62.6,55.1,54.1,53.0,52.7, 38.5。
HRMS(ESI):m/z calcd for C28H27O9:507.1650[M+H]+,found:507.1654。
example 3
Synthesis of methyl 2' -p-methoxyphenyl-5 ' - (2-methylpropen-1-yl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxin-5, 1' -cyclopentane) -3',3' -dicarboxylate (IIIc) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, a 5mL flask was charged with (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), methyl 2- (2-methylpropen-1-yl) cyclopropane-1, 1-dicarboxylate (IIc) (21.2mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol) in this order, and then anhydrous acetonitrile (1.0mL) was added to the reaction system and the reaction was stirred at room temperature for 18 hours; after the reaction was completed, it was quenched with water (3mL), then extracted with ethyl acetate (3 × 4mL), the organic phases were combined, the organic phases were dried over anhydrous sodium sulfate, then the solvent was removed by rotary evaporation, and the resulting crude product was separated and purified by column chromatography (eluent ethyl acetate: petroleum ether ═ 1:5, v/v) to give 31.8mg of methyl 2' -p-methoxyphenyl-5 ' - (2-methylpropen-1-yl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (iiic) as a white solid in 68% yield.
The characterization data of the product (IIIc) obtained are as follows:
white solid (31.8mg, 68% yield);1H NMR(400MHz,CDCl3)δ7.07(d,J＝8.4Hz,2H),6.69 (d,J＝8.7Hz,2H),6.32(s,1H),5.75(s,1H),5.67(s,1H),5.40(s,1H),4.90(d,J＝9.5Hz,1H), 4.74(s,1H),3.74(s,3H),3.72(s,3H),3.50–3.40(m,1H),3.36(s,3H),2.92(t,J＝7.5Hz,1H), 2.40(dd,J＝14.4,7.5Hz,1H),1.61(s,3H),1.54(s,3H)。
13C NMR(100MHz,CDCl3)δ199.3,172.7,172.4,163.1,158.7,144.7,135.8,130.9,128.0, 121.7,113.0,104.5,101.1,99.7,65.7,63.0,62.0,55.0,52.9,52.5,50.1,39.4,25.9,18.3。
HRMS(ESI):m/z calcd for C26H29O8:469.1857[M+H]+,found:469.1855。
example 4
Synthesis of ethyl 5 '-p-methoxyphenyl-2' -methyl-2 '-vinyl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -4',4' -dicarboxylate (IIId) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, to a 5mL flask were added in this order (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), ethyl 2-methyl-2-vinylcyclopropyl-1, 1-dicarboxylate (IId) (19.8mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol), and then to the reaction system was added anhydrous acetonitrile (1.0mL) and the reaction was stirred at room temperature for 16 hours; after the reaction was completed, quenched with water (3mL), then extracted with ethyl acetate (3 × 4mL), the organic phases were combined, dried over anhydrous sodium sulfate, and then the solvent was removed by rotary evaporation, and the resulting crude product was separated and purified by column chromatography (eluent ethyl acetate: petroleum ether ═ 1:5, v/v) to give 37.6mg of 5 '-p-methoxyphenyl-2' -methyl-2 '-vinyl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxin-5, 1' -cyclopentane) -4',4' -dicarboxylic acid ethyl ester (iiid) as a white solid, yield 78%.
The characterization data of the product (IIId) obtained are as follows:
white solid (37.6mg, 78% yield);1H NMR(400MHz,CDCl3)δ7.20(d,J＝8.7Hz,2H),6.69 (d,J＝8.7Hz,2H),6.38(s,1H),5.83–5.74(m,2H),5.70(s,1H),5.48(s,1H),5.27(s,1H),4.97 (dd,J＝14.1,6.1Hz,2H),4.24(q,J＝12.0Hz,2H),4.00–3.92(m,1H),3.72(s,3H),3.62-3.54 (m,1H),3.39(d,J＝14.3Hz,1H),2.25(d,J＝14.3Hz,1H),1.25(t,J＝7.1Hz,3H),1.13(s,3H), 0.81(t,J＝7.1Hz,3H)。
13C NMR(100MHz,CDCl3)δ196.6,172.7,171.9,162.9,158.6,144.1,141.9,131.5,128.7, 113.5,113.1,107.0,101.3,100.1,67.1,62.4,61.7,55.2,55.1,53.4,45.4,23.6,14.0,13.4。
HRMS(ESI):m/z calcd for C27H31O8:483.2013[M+H]+,found:483.2015。
example 5
Synthesis of methyl 2' -p-methoxyphenyl-6 ' - ((E) -p-methoxystyryl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxin-5, 1' -cyclane) -3',3' -dicarboxylate (IIIe) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, to a 5mL flask were added (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), methyl 2- (E) -p-methoxystyrylcyclobutylalkyl-1, 1-dicarboxylate (IIe) (30.4mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol) in this order, and then to the reaction system was added anhydrous acetonitrile (1.0mL) and the reaction was stirred at room temperature for 18 hours; after the reaction was complete, quenched with water (3mL), extracted with ethyl acetate (3 × 4mL), the organic phases were combined, dried over anhydrous sodium sulfate and the solvent was removed by rotary evaporation, and the crude product obtained was purified by column chromatography (eluent ethyl acetate: petroleum ether ═ 1:5, v/v) to give methyl 2' -p-methoxyphenyl-6 ' - ((E) -p-methoxystyryl) -6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclohexane) -3',3' -dicarboxylate (iii E)43.2mg as a white solid in 77% yield.
The characterization data of the product (IIIe) obtained are as follows:
white solid (43.2mg, 77% yield);1H NMR(400MHz,CDCl3)δ7.13(dd,J＝8.7,3.8Hz,4H), 6.78(d,J＝8.7Hz,2H),6.63(d,J＝8.8Hz,2H),6.24(d,J＝15.8Hz,1H),6.16(s,1H),5.75– 5.69(m,1H),5.68(s,1H),5.65(s,1H),5.22(s,1H),3.98(s,1H),3.77(s,3H),3.73(s,3H),3.72(s, 3H),3.53(s,3H),3.03–2.94(m,1H),2.63(dd,J＝12.0,4.2Hz,1H),2.21–2.13(m,2H),1.85– 1.77(m,1H)。
13C NMR(100MHz,CDCl3)δ201.2,172.7,171.8,162.3,158.9,158.3,145.4,132.4,130.6, 130.1,128.7,127.3,126.7,113.8,112.0,104.9,101.0,99.9,59.1,57.9,55.6,55.3,54.9,52.5,52.0, 51.2,34.2,24.8。
HRMS(ESI):m/z calcd for C32H33O9:561.2119[M+H]+,found:561.2119。
example 6
Synthesis of methyl 2' - (2, 4-dimethoxyphenyl) -5' - (E) -styryl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (IIIf) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, a 5mL flask was charged with (E) -6- (2, 4-dimethoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ib) (28.6mg,0.1mmol), methyl 2- (E) -styrylcyclopropyl-1, 1-dicarboxylate (IIa) (26.0mg,0.1mmol) and lithium iodide (1.1mg,0.008mmol) in this order, and then anhydrous acetonitrile (1.0mL) was added to the reaction system and the reaction was stirred at room temperature for 18H; after the reaction was complete, quenched with water (3mL), then extracted with ethyl acetate (3 × 4mL), the organic phases were combined, dried over anhydrous sodium sulfate and the solvent was removed on a rotary evaporator and the crude product obtained was purified by column chromatography (eluent ethyl acetate: petroleum ether ═ 1:5, v/v) to give methyl 2' - (2, 4-dimethoxyphenyl) -5' - (E) -styryl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (iiif) 43.7mg as a white solid in 80% yield.
The characterization data of the product (IIIf) obtained are as follows:
white solid (43.7mg, 80% yield);1H NMR(400MHz,CDCl3)δ7.13(dd,J＝8.7,3.8Hz,4H), 6.78(d,J＝8.7Hz,2H),6.63(d,J＝8.8Hz,2H),6.24(d,J＝15.8Hz,1H),6.16(s,1H),5.75– 5.69(m,1H),5.68(s,1H),5.65(s,1H),5.22(s,1H),3.98(s,1H),3.77(s,3H),3.73(s,3H),3.72(s, 3H),3.53(s,3H),3.03–2.94(m,1H),2.63(dd,J＝12.0,4.2Hz,1H),2.21–2.13(m,2H),1.85– 1.77(m,1H)。
13C NMR(100MHz,CDCl3)δ198.8,172.5,172.3,163.0,159.8,159.0,144.3,137.1,132.0, 131.0,128.4,127.3,127.2,126.3,116.9,104.8,103.5,101.1,99.5,98.5,65.9,62.3,56.0,55.6,55.1, 53.0,52.9,52.5,38.7。
HRMS(ESI):m/z calcd for C31H31O9:547.1963[M+H]+,found:547.1967。
comparative example 1
Synthesis of methyl 2' -p-methoxyphenyl-5 ' - (E) -styryl-6-oxo-6H-spiro (benzo [ d ] [1,3] dioxine-5, 1' -cyclopentane) -3',3' -dicarboxylate (IIIa) according to the following reaction scheme:
the preparation method comprises the following specific steps: in a glove box filled with nitrogen, to a 5mL flask were added sequentially (E) -6- (p-methoxybenzylidene) benzo [ d ] [1,3] dioxin-5 (6H) -one (Ia) (25.6mg,0.1mmol), methyl 2- (E) -styrylcyclopropanyl-1, 1-dicarboxylate (IIa) (26.0mg,0.1mmol) and lithium chloride (2.1mg,0.05mmol), and then to the reaction system was added anhydrous acetonitrile (1.0mL) and the reaction was stirred at room temperature for 18H, and it was monitored that no product IIIa was produced while the starting material was not consumed. The reaction was then heated to 60 ℃ in an oil bath and stirred for 8h, monitoring showing that no product IIIa was formed.
In this comparative example, no spiro compound was obtained using lithium chloride as a catalyst.
The above embodiments are only some examples of the present invention, and not intended to limit the present invention in any way, and any simple modification, equivalent change and modification made to the above embodiments according to the technical spirit of the present invention are all included in the technical scope of the present invention.
Claims (10)
1. A method for synthesizing spiro compounds by catalysis of lithium iodide comprises the following steps:
in a solvent, under the catalysis of lithium iodide, carrying out cyclization reaction on an o-quinone methide I and a vinyl cycloparaffin compound II to obtain a spiro compound III;
wherein:
R1is phenyl, 4-methoxyphenyl, 3, 4-dimethoxyphenyl or 2, 4-dimethoxyphenyl;
R2is phenyl, benzyl, methyl, ethyl, isopropyl or tert-butyl;
R3is hydrogen or benzenePhenyl, 4-methoxyphenyl, 4-bromophenyl, benzyl, furyl, thienyl, methyl, ethyl or dimethyl;
R4is hydrogen, phenyl, methyl, ethyl or isopropyl;
n is 1 or 2.
2. The method for the catalytic synthesis of spiro-compounds with lithium iodide as claimed in claim 1, wherein the solvent is dichloromethane, 1, 2-dichloroethane, 1, 4-dioxane, acetone, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, benzyl acetate, tert-butyl acetate, ethyl benzoate, toluene, ethylbenzene or chlorobenzene; the solvent is subjected to anhydrous treatment.
3. The method for the catalytic synthesis of spiro-compounds via lithium iodide according to claim 2, wherein the solvent is acetonitrile, ethyl acetate or tetrahydrofuran.
4. The method for the catalytic synthesis of spiro compounds via lithium iodide according to claim 1, wherein the ratio of the volume of the solvent to the moles of o-quinone methide I is 5-15mL:1 mmol.
5. The method for the catalytic synthesis of spiro compounds via lithium iodide according to claim 1, wherein the molar ratio of lithium iodide to o-quinone methide I is 0.05-0.1: 1.
6. The method for the catalytic synthesis of spiro-compounds with lithium iodide as claimed in claim 1, wherein the molar ratio of o-quinone methide I and vinylcycloalkane II is 1-1.5: 1.
7. The method for the catalytic synthesis of spiro-compounds via lithium iodide according to claim 1, wherein the ring-closure reaction temperature is 0 ℃ to room temperature; the cyclization reaction time is 0.5-36 h.
8. The method for the catalytic synthesis of spiro compounds via lithium iodide according to claim 7, wherein the cyclization reaction time is 8-18 h.
9. The method for the catalytic synthesis of spiro-compounds via lithium iodide according to claim 1, wherein the cyclization reaction is carried out under nitrogen atmosphere.
10. The method for the catalytic synthesis of spiro-compounds with lithium iodide as claimed in claim 1, wherein the post-treatment of the reaction solution obtained after the cyclization reaction of o-quinone methide I and vinylcycloalkane II is as follows: adding water into the reaction liquid to quench the reaction, extracting with ethyl acetate, drying the obtained organic phase with anhydrous sodium sulfate, removing the solvent to obtain a crude product, separating and purifying the crude product by silica gel column chromatography to obtain the spiro compound III, wherein the eluent is a mixed solvent of ethyl acetate, dichloromethane and petroleum ether, and the volume ratio of the ethyl acetate, the dichloromethane and the petroleum ether in the mixed solvent of the ethyl acetate, the dichloromethane and the petroleum ether is 0.05-0.25:0-0.2: 1.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110680838.XA CN113372324A (en) | 2021-06-18 | 2021-06-18 | Method for synthesizing spiro compound through lithium iodide catalysis |
| CN202210676292.5A CN114989132B (en) | 2021-06-18 | 2022-06-15 | Method for synthesizing spiro compounds through lithium iodide catalysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110680838.XA CN113372324A (en) | 2021-06-18 | 2021-06-18 | Method for synthesizing spiro compound through lithium iodide catalysis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113372324A true CN113372324A (en) | 2021-09-10 |
Family
ID=77577803
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110680838.XA Pending CN113372324A (en) | 2021-06-18 | 2021-06-18 | Method for synthesizing spiro compound through lithium iodide catalysis |
| CN202210676292.5A Active CN114989132B (en) | 2021-06-18 | 2022-06-15 | Method for synthesizing spiro compounds through lithium iodide catalysis |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210676292.5A Active CN114989132B (en) | 2021-06-18 | 2022-06-15 | Method for synthesizing spiro compounds through lithium iodide catalysis |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN113372324A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101575329A (en) * | 2009-06-02 | 2009-11-11 | 重庆福安药业有限公司 | Preparation method of tetrahydrothiophene-3-ketone and intermediate |
| CN110128400A (en) * | 2019-05-23 | 2019-08-16 | 兰州大学 | A kind of preparation method of spiro[bicyclo[3.2.0]heptene-2,1'-cyclobutane] compound |
| CN111116551A (en) * | 2020-01-03 | 2020-05-08 | 中国医科大学 | 1-azaspiro [5.5] undecan-3-ones and 1-azaspiro [5.5] undecan-3-ols |
| CN111170918A (en) * | 2020-01-21 | 2020-05-19 | 山东大学 | A kind of method for synthesizing γ-lactam and δ-lactam by C-H amination |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3300774A1 (en) * | 1983-01-12 | 1984-07-12 | Hoechst Ag, 6230 Frankfurt | NEW SPIROCYCLIC AMINO ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THE USE THEREOF AND NEW SPIROCYCLIC AMINO ACIDS AS INTERMEDIATE PRODUCTS AND METHOD FOR THE PRODUCTION THEREOF |
| DE102006057036A1 (en) * | 2006-12-04 | 2008-06-05 | Bayer Cropscience Ag | New biphenyl substituted spirocyclic ketoenol derivatives useful for the manufacture of herbicides and for combating parasites |
| US11952327B2 (en) * | 2016-09-15 | 2024-04-09 | University Of Florida Research Foundation, Inc. | Methods and compositions for terpenoid synthesis |
| CN109438190B (en) * | 2018-11-29 | 2021-05-28 | 南京大学 | A kind of activation method and application of phenol derivatives catalyzed by Lewis acid |
| CN110724164B (en) * | 2019-10-30 | 2022-06-28 | 浙江九洲药业股份有限公司 | Preparation method and application of 3-substituted chiral spiro aminophosphine ligand on pyridine ring |
-
2021
- 2021-06-18 CN CN202110680838.XA patent/CN113372324A/en active Pending
-
2022
- 2022-06-15 CN CN202210676292.5A patent/CN114989132B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101575329A (en) * | 2009-06-02 | 2009-11-11 | 重庆福安药业有限公司 | Preparation method of tetrahydrothiophene-3-ketone and intermediate |
| CN110128400A (en) * | 2019-05-23 | 2019-08-16 | 兰州大学 | A kind of preparation method of spiro[bicyclo[3.2.0]heptene-2,1'-cyclobutane] compound |
| CN111116551A (en) * | 2020-01-03 | 2020-05-08 | 中国医科大学 | 1-azaspiro [5.5] undecan-3-ones and 1-azaspiro [5.5] undecan-3-ols |
| CN111170918A (en) * | 2020-01-21 | 2020-05-19 | 山东大学 | A kind of method for synthesizing γ-lactam and δ-lactam by C-H amination |
Non-Patent Citations (2)
| Title |
|---|
| CHAO MA等: "Stereoselective 1,6-Conjugate Addition/Annulation of para -Quinone Methides with Vinyl Epoxides/Cyclopropanes", 《ACS CATAL.》 * |
| ZHENBO YUAN等: "Bifunctional Organo/Metal Cooperatively Catalyzed [3+2] Annulation of para -Quinone Methides with Vinylcyclopropanes: Approach to Spiro[4.5]deca-6,9-diene-8-ones", 《ORG. LETT.》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114989132A (en) | 2022-09-02 |
| CN114989132B (en) | 2023-09-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | One-pot, highly efficient, asymmetric synthesis of ring-fused piperidine derivatives bearing N, O-or N, N-acetal moieties | |
| JP5674059B2 (en) | Catalyst for hydrogen transfer reaction containing ruthenium complex and method for producing hydrogen transfer reactant | |
| CN115784906B (en) | Method for preparing triarylmethane derivative by high-selectivity Friedel-crafts arylation reaction | |
| CN111848630A (en) | Method for preparing pyrrolo[1,2-a]indole compounds based on alkynyl-substituted aza-p-methylenebenzoquinone | |
| CN114773174A (en) | Synthetic method of α-deuterated carbonyl compounds | |
| Jia et al. | [6+ 3] Annulations of Morita–Baylis–Hillman carbonates and dicyanoheptafulvene | |
| CN110437129A (en) | A kind of straightforward procedure synthesizing 3- ether isoindoline ketone compound | |
| CN108976243A (en) | Spiral shell-chroman -4,3 '-Oxoindole synthetic method is synthesized with the hydroxy-benzyl alcohol of neighbour containing Oxoindole by dimethyl furan | |
| JP7464234B2 (en) | Method for producing highly optically active allene carboxylic acid compounds having axial asymmetry | |
| CN113620918B (en) | Method for synthesizing spiro compounds through Lewis acid catalyzed [3+2] cycloaddition reaction | |
| Prashanth et al. | Rh (iii)-catalyzed sequential spiroannulation/lactonization of 3-aryl N-sulfonyl ketimines with 4-hydroxy-2-alkynoates by C–H bond activation | |
| CN109608471B (en) | Synthetic method of chiral spiro-epoxy indole compounds | |
| CN114805182A (en) | Method for synthesizing indole spiro cyclopropane compound by visible light catalysis | |
| CN111499542B (en) | A kind of preparation method of cycloalkenone compound containing α-cyano group substituted quaternary carbon center | |
| CN102180886B (en) | Asymmetric catalytic synthesis method for Galanthamine | |
| CN113372324A (en) | Method for synthesizing spiro compound through lithium iodide catalysis | |
| Domain et al. | Stereocontrol in Conformationally Stable C (sp2)─ C (sp3) Atropisomers | |
| Min et al. | Optically Active 3, 4-Dihydrocoumarins via Organocatalyzed Asymmetric [4+ 2] Annulation of ortho-Hydroxyl Functionalized p-Quinone Methides with β-Keto Acylpyrazoles | |
| CN107098902B (en) | A kind of synthetic method of pyrrolo[1,2-a]quinoline derivative | |
| CN104086477A (en) | Preparation method of optical-activity spiropentyl-1,3'-indole and derivatives thereof | |
| CN102766095B (en) | Preparation method of electron-deficient group-containing multi-substituted pyrazole derivative | |
| Zhang | Synthesis of Diarylmethanes via Pd-Catalyzed Coupling of Aryltosylates with Benzyltitanium Reagents | |
| CN105348062A (en) | Preparation method of 3-aryl-1-indanone derivate | |
| CN111732552A (en) | A kind of method for palladium-catalyzed synthesis of 1,3-oxazole-2-thione | |
| CN109384753B (en) | A kind of synthetic method of 2-phenyl-3-methylbenzofuran compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210910 |
|
| WD01 | Invention patent application deemed withdrawn after publication |