CN117659065A - Method for preparing beta-boron-substituted aldehyde derivative - Google Patents
Method for preparing beta-boron-substituted aldehyde derivative Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 33
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title claims abstract 7
- 150000001336 alkenes Chemical class 0.000 claims abstract description 26
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052796 boron Inorganic materials 0.000 claims abstract description 21
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 12
- -1 diboron compound Chemical class 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 239000002994 raw material Substances 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 8
- 239000003446 ligand Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 claims description 7
- 230000035484 reaction time Effects 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 239000003513 alkali Substances 0.000 claims description 5
- 229940125782 compound 2 Drugs 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- DFPLUISJTGAKGA-UHFFFAOYSA-N C1=C(C=C(C(=C1C)N1C=CN(C1=C)C1=C(C)C=C(C)C=C1C)C)C Chemical compound C1=C(C=C(C(=C1C)N1C=CN(C1=C)C1=C(C)C=C(C)C=C1C)C)C DFPLUISJTGAKGA-UHFFFAOYSA-N 0.000 claims description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 229940076286 cupric acetate Drugs 0.000 claims description 2
- 229960003280 cupric chloride Drugs 0.000 claims description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052731 fluorine Chemical group 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 2
- CLKUPZYLSZLSSN-UHFFFAOYSA-N methylidenecopper Chemical compound [Cu]=C CLKUPZYLSZLSSN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- AXXHQFCYSIOBDM-UHFFFAOYSA-N 1-(2-propan-2-ylphenyl)naphthalene Chemical compound CC(C)C1=CC=CC=C1C1=CC=CC2=CC=CC=C12 AXXHQFCYSIOBDM-UHFFFAOYSA-N 0.000 claims 1
- NCSZRNMVUILZEC-UHFFFAOYSA-N 3-methylidene-1,2-dihydroindene Chemical compound C1=CC=C2C(=C)CCC2=C1 NCSZRNMVUILZEC-UHFFFAOYSA-N 0.000 claims 1
- AUIURIPXSQBMJD-UHFFFAOYSA-N 4-methylidene-2,3-dihydro-1h-naphthalene Chemical compound C1=CC=C2C(=C)CCCC2=C1 AUIURIPXSQBMJD-UHFFFAOYSA-N 0.000 claims 1
- 150000001503 aryl iodides Chemical class 0.000 claims 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000011010 flushing procedure Methods 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052802 copper Inorganic materials 0.000 abstract description 3
- 239000010949 copper Substances 0.000 abstract description 3
- 238000005810 carbonylation reaction Methods 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
- 239000011734 sodium Substances 0.000 description 19
- 238000001228 spectrum Methods 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 230000005311 nuclear magnetism Effects 0.000 description 11
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000004896 high resolution mass spectrometry Methods 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 239000007789 gas Substances 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- FHONALAGHNALCH-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol methanol Chemical compound FC(C(C(F)(F)F)O)(F)F.CO FHONALAGHNALCH-UHFFFAOYSA-N 0.000 description 1
- HHJJEPKLXMKELN-UHFFFAOYSA-N 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide Chemical compound CC1=C(C=CC=C1B1OC(C(O1)(C)C)(C)C)S(=O)(=O)N HHJJEPKLXMKELN-UHFFFAOYSA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a process for preparing beta-boron-substituted aldehyde derivatives. Specifically, under the condition of copper catalysis, diboron compound, olefin and carbon monoxide are prepared into beta-boron substituted aldehyde derivatives through a one-pot method. The invention starts from simple and easily obtained raw materials and catalysts, and a series of beta-boron-substituted aldehyde derivatives are obtained through carbonylation reaction.
Description
Technical Field
The invention relates to a method for synthesizing beta-boron substituted aldehyde derivative compounds.
Background
Beta-boron substituted aldehyde derivatives are important aldehyde derivatives which are widely used in natural products and medicines, have biological activity and insecticidal activity, and are also important components of organic synthesis and functional materials.
Traditional synthesis of such compounds requires the use of stoichiometric amounts of coupling reagents, greatly limiting their synthetic applications. In addition, regioselectivity and stereoselectivity control of the product are also an important factor limiting development.
Up to now, the one-step synthesis of the beta-boron-substituted aldehyde derivative compound is not reported, the steps of the traditional multi-step synthesis method are complicated, and the beta-boron-substituted aldehyde derivative is prepared through direct regional and stereoselectivity of olefin, diboron compound and bulk chemical carbon monoxide.
In summary, a process for the efficient, atom-economical, regioselective preparation of beta-boron-substituted aldehyde derived compounds is described herein.
Disclosure of Invention
The invention aims to provide a method for synthesizing beta-boron substituted aldehyde compounds.
Reaction equation 1: synthesis of beta-boron substituted aldehyde derivative
The specific operation steps are as follows (reaction equation 1):
firstly adding a catalyst, a ligand, alkali, alcohol, olefin 1, diboron compound 2 and a solvent into a reaction kettle, then replacing the atmosphere in the reaction kettle with carbon monoxide 3 gas, and after replacement, charging 5-50bar of carbon monoxide gas, and reacting at 50-120 ℃, preferably 70-100 ℃; the reaction time is 28 to 36 hours, preferably 20 to 24 hours; and after the reaction is finished, separating by column chromatography to obtain the beta-boron substituted aldehyde 4.
The olefin 1 is used in a proportion of 0.1 to 10mmol, preferably 0.2mmol.
The amount ratio of diboron compound 2 is 0.15 to 15mmol, preferably 0.3mmol.
The catalyst is one or more than two of cuprous chloride, cupric acetate, cupric bromide and carbene copper complex, preferably cupric chloride; the catalyst is used in an amount of 1 to 10mol%, preferably 5mol%, based on the amount of olefin 1.
The ligand is one or more than two of triphenylphosphine, 1, 2-bis (diphenylphosphine) ethane, 1' -bis (diphenylphosphine) ferrocene, 4, 5-bis (diphenylphosphine) -9, 9-dimethyl xanthene, 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) -4, 5-dihydro-imidazole and 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) imidazole; the amount of ligand is 1 to 10mol%, preferably 5mol% of the amount of olefin 1.
The alkali is one or more of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, potassium methoxide and sodium ethoxide, preferably potassium p-tert-butoxide; the amount of base is 100 to 400mol%, preferably 300mol%, based on the amount of olefin 1.
The alcohol is one or more of tert-butanol, methanol, ethanol and butanol, preferably p-tert-butanol; the amount of alcohol is 100 to 400mol%, preferably 200mol%, of the amount of olefin 1.
The solvent is one or more of n-hexane, tetrahydrofuran, toluene, diethyl ether, methyl tert-butyl ether, 1, 4-dioxane and 1, 2-dichloroethane, preferably tetrahydrofuran; the solvent is used in an amount of 1.0 to 10.0 ml, preferably 5.0 ml, per millimole of olefin 1.
The invention has the following advantages:
the invention synthesizes a series of beta-boron substituted aldehyde compounds by copper catalyzed alkene boronation and carbonylation.
First, the reaction has a very high regioselectivity. Secondly, the reaction is directly and efficiently carried out, and the economy of the reaction step is realized. Finally, the functional group compatibility of the reaction system is good, and the beta-boron substituted aldehyde compound containing the quaternary carbon center can be constructed in one step.
Detailed Description
For a better understanding of the present invention, it is illustrated by the following examples. The starting materials and results for examples 1-10 are shown in Table 1.
TABLE 1 reaction results of different substituted olefins
Example 1
The reaction was carried out in a reaction vessel, first, 0.01mmol (5 mol% of the amount of olefin 1 a) of catalyst cuprous chloride, 0.01mmol (5 mol% of the amount of olefin 1 a) of ligand 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) -4, 5-dihydro-imidazole, potassium tert-butoxide (300 mol% of the amount of olefin 1 a), 1a (0.2 mmol) of olefin, 2 (0.3 mmol) of bispinacol borate, 0.4mmol of tert-butanol and tetrahydrofuran (1.0 mL) of solvent were added, the total charge of these materials in the reaction vessel was 10% of the volume of the reaction vessel, then three times of carbon monoxide 3 gas was purged and carbon monoxide gas was purged into the reaction vessel, followed by 5bar of carbon monoxide gas. The reaction was carried out at 80℃for 24 hours. After the reaction is finished, the yield of the compound 4a is 63% through column chromatography separation, and the compound is subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum and boron spectrum) and high-resolution mass spectrum identification structure.
The detection data are as follows:
2-Methyl-2-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4a)：34.5mg,63％yield,yellow oil.Eluent:pentane/ethyl acetate＝50/1-20/1. 1 H NMR(700MHz,CDCl 3 )δ9.51(s,1H),7.34(t,J＝7.7Hz,2H),7.29(d,J＝7.9Hz,2H),7.25(dd,J＝13.1,5.8Hz,1H),1.57(s,3H),1.44(d,J＝15.5Hz,1H),1.34(d,J＝15.5Hz,1H),1.13(s,6H),1.12(s,6H).
13 C NMR(176MHz,CDCl 3 )δ202.47,202.45,141.7,128.6,127.0,83.2,52.0,24.7,24.6,21.5.
11 B NMR(128MHz,CDCl 3 )δ33.31.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 16 H 23 BO 3 Na 297.1635；Found:297.1643.
example 2
The procedure and conditions were as in example 1, except that the yields of starting materials 1,4b shown in Table 1 were 57%, and the compounds were subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum and boron spectrum) and high resolution mass spectrometry to identify the structures.
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(p-tolyl)propanal(4b)
32.8mg,57％yield,slight yellow oil.Eluent:pentane/ethyl acetate＝50/1-20/1. 1 H NMR(700MHz,CDCl 3 )δ9.47(s,1H),7.16(q,J＝8.3Hz,4H),2.32(s,3H),1.55(s,3H),1.36(dd,J＝40.2,15.5Hz,2H),1.15(s,5H),1.14(s,6H). 13 C NMR(176MHz,CDCl 3 )δ202.52,202.51,138.6,136.7,129.3,126.9,83.2,51.7,24.7,24.7,21.5,20.9.
11 B NMR(128MHz,CDCl 3 )δ33.79.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 17 H 25 BO 3 Na 311.1792；Found:311.1799.
Example 3
The procedure and conditions were as in example 1, except that the yields of starting materials 1,4c shown in Table 1 were 56%, and the compounds were subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum and boron spectrum) and high resolution mass spectrometry to identify the structures.
2-(4-(tert-Butyl)phenyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4c)
37.0mg,56％yield,yellow oil.Eluent:pentane/ethyl acetate＝50/1-20/1.
1 H NMR(400MHz,CDCl 3 )δ9.49(s,1H),7.36(d,J＝8.3Hz,2H),7.21(d,J＝8.2Hz,2H),1.56(s,3H),1.38(d,J＝25.6Hz,2H),1.30(s,9H),1.13(s,6H),1.11(s,6H).
13 C NMR(101MHz,CDCl 3 )δ202.6,149.9,138.5,126.7,125.5,83.2,51.6,34.4,31.3,24.7,24.6,21.3.
11 B NMR(128MHz,CDCl 3 )δ33.44.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 20 H 31 BO 3 Na 353.2262；Found:353.2261.
Example 4
The procedure and conditions were as in example 1, except that the starting materials 1,4d shown in Table 1 were 55% recovered and the compounds were subjected to nuclear magnetism (hydrogen, carbon and boron) and high resolution mass spectrometry to identify the structure.
2-(4-Methoxyphenyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4d)
33.4mg,55％yield,colorless oil.Eluent:pentane/ethyl acetate＝20/1-10/1.
1 H NMR(700MHz,CDCl 3 )δ9.44(s,1H),7.20(d,J＝8.8Hz,2H),6.88(d,J＝8.8Hz,2H),3.79(s,3H),1.54(s,3H),1.41(d,J＝15.5Hz,1H),1.31(d,J＝15.5Hz,1H),1.14(s,12H).
13 C NMR(176MHz,CDCl 3 )δ202.4,158.6,133.5,128.2,114.0,83.2,55.3,51.3,24.7,24.7,21.5.
11 B NMR(128MHz,CDCl 3 )δ33.37.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 17 H 25 BO 4 Na 327.1741；Found:327.1739.
Example 5
The procedure and conditions were as in example 1, except that the starting materials 1,4e shown in Table 1 were 48% recovered and the compounds were subjected to nuclear magnetism (hydrogen, carbon, fluorine and boron), high resolution mass spectrometry to identify the structure.
2-(4-Fluorophenyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4e)
28.0mg,48％yield,colorless oil.Eluent:pentane/ethyl acetate＝50/1-20/1.
1 H NMR(700MHz,CDCl 3 )δ9.47(s,1H),7.25(dd,J＝8.5,5.7Hz,2H),7.03(t,J＝8.5Hz,2H),1.56(s,3H),1.37(dd,J＝83.4,15.5Hz,2H),1.13(s,12H).
13 C NMR(176MHz,CDCl 3 )δ202.1,161.9(d,J＝246.2Hz),137.3,128.7(d,J＝8.0Hz),115.4(d,J＝21.1Hz),83.3,51.4,24.7,24.6,21.6.
19 F NMR(376MHz,CDCl 3 )δ-115.92.
11 B NMR(128MHz,CDCl 3 )δ33.44.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 16 H 22 BFO 3 Na 315.1541；Found:315.1548.
Example 6
The procedure and conditions were as in example 1, except that the yield of starting materials 1,4f shown in Table 1 was 55%, and the compounds were subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum and boron spectrum) and high resolution mass spectrometry to identify the structure.
2-Methyl-2-(naphthalen-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4f)
35.6mg,55％yield,pale yellow oil.Eluent:pentane/ethyl acetate＝50/1-20/1. 1 H NMR(400MHz,CDCl 3 )δ9.74(s,1H),7.92–7.71(m,3H),7.65–7.57(m,1H),7.51–7.41(m,3H),1.75(s,3H),1.69(d,J＝15.5Hz,1H),1.48(d,J＝15.5Hz,1H),1.15(s,6H),1.10(s,6H).
13 C NMR(101MHz,CDCl 3 )δ205.7,138.5,134.6,131.3,129.4,128.7,126.4,125.4,125.2,124.7,83.2,53.0,24.8,24.7,23.3.
11 B NMR(128MHz,CDCl 3 )δ33.11.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 20 H 25 BO 3 Na 347.1792；Found:347.1799.
Example 7
The procedure and conditions were as in example 1, except that the 1,4g yield of starting material from Table 1 was 53%, and the compounds were subjected to nuclear magnetism (hydrogen, carbon and boron) and high resolution mass spectrometry to identify the structure.
2-(3,5-Dimethylphenyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4g)
32.1mg,53％yield,colorless oil.Eluent:pentane/ethyl acetate＝50/1-20/1.
1 H NMR(700MHz,CDCl 3 )δ9.47(s,1H),6.88(s,3H),2.30(s,6H),1.54(s,3H),1.35(dd,J＝36.5,15.5Hz,2H),1.15(s,6H),1.15(s,6H).
13 C NMR(176MHz,CDCl 3 )δ202.7,202.6,141.6,138.1,128.6,124.8,83.2,51.9,24.7,24.7,21.6,21.4.
11 B NMR(128MHz,CDCl 3 )δ33.57.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 18 H 27 BO 3 Na 325.1948；Found:325.1947.
Example 8
The procedure and conditions were as in example 1, except that the starting materials 1,4h yield of Table 1 was 65%, and the compounds were subjected to nuclear magnetism (hydrogen, carbon and boron) and high resolution mass spectrometry to identify the structure.
1-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-1,2,3,4-tetrahydronaphthalene-1-carbaldehyde(4h)
39.0mg,65％yield,colorless oil.Eluent:pentane/ethyl acetate＝50/1-20/1.
1 H NMR(400MHz,CDCl 3 )δ9.49(s,1H),7.22–7.02(m,4H),2.90–2.69(m,2H),2.18–2.05(m,2H),1.95–1.74(m,2H),1.43(d,J＝15.4Hz,1H),1.23(d,J＝10.9Hz,1H),1.12(s,6H),1.09(s,6H).
13 C NMR(101MHz,CDCl 3 )δ202.5,138.3,136.40,129.5,128.7,126.8,126.2,83.1,51.76,23.0,29.6,24.7,24.6,19.6.
11 B NMR(128MHz,CDCl 3 )δ32.99.
HRMS(ESI-FT-ICR)m/z:[M+H] + Calcd for C 18 H 26 BO 3 301.1972；Found:301.1973.
Example 9
The procedure and conditions were as in example 1, except that the yield of starting materials 1,4i shown in Table 1 was 58% and the compounds were subjected to nuclear magnetism (hydrogen, carbon and boron) and high resolution mass spectrometry to identify the structure.
2-Phenyl-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)butanal(4i)
33.4mg,58％yield,pale yellow oil.Eluent:pentane/ethyl acetate＝50/1-20/1. 1 H NMR(400MHz,CDCl 3 )δ9.62(s,1H),7.41–7.31(m,2H),7.25(m,3H),2.17–1.91(m,2H),1.43(q,J＝15.7Hz,2H),1.14(s,6H),1.12(s,6H),0.76(t,J＝7.4Hz,3H).
13 C NMR(101MHz,CDCl 3 )δ203.52,140.50,128.50,127.51,126.90,83.29,55.91,28.26,24.67,8.51.
11 B NMR(128MHz,CDCl 3 )δ33.28.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 17 H 25 BO 3 Na 311.1792；Found:311.1797.
Example 10
The procedure and conditions were as in example 1, except that the yield of starting materials 1,4j shown in Table 1 was 40%, and the compounds were subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum and boron spectrum) and high resolution mass spectrometry to identify the structure.
2-Cyclohexyl-2-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanal(4j)
27.3mg,40％yield,colorless oil.Eluent:pentane/ethyl acetate＝50/1-20/1.
1 H NMR(400MHz,CDCl 3 )δ9.88(s,1H),7.38–7.28(m,2H),7.24(m,3H),2.03(t,J＝11.9Hz,1H),1.80–1.60(m,4H),1.52–1.21(m,8H),1.13(s,6H),1.07(s,6H).
13 C NMR(101MHz,CDCl 3 )δ205.1,140.3,128.1,128.1,126.6,100.0,83.3,59.0,44.9,28.6,28.1,26.9,26.5,24.7,24.5.
11 B NMR(128MHz,CDCl 3 )δ33.48.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 21 H 31 BO 3 Na 365.2262；Found:365.2275.
Product application example
Compound 4a (54.8 mg), iodobenzene (45 mg), potassium carbonate (41.4 mg) and Pd (PPh) 3 ) 4 (2.4 mg), N-dimethylformamide (3.0 ml) and water (0.45 ml) were added to the flask, and the mixture was degassed three times with nitrogen. The reaction was allowed to react at 80℃for 3 hours. After the completion of the reaction, a colorless oily product 5 (33.2 mg) was isolated in 74% yield. Compound 5 was subjected to nuclear magnetism (hydrogen spectrum, carbon spectrum) and high resolution mass spectrometry to identify the structure. 1 H NMR(400MHz,CDCl 3 )δ9.63(s,1H),7.34(ddd,J＝18.4,7.9,6.4Hz,3H),7.16(m,5H),6.79(dd,J＝6.4,3.0Hz,2H),3.20(q,J＝13.6Hz,2H),1.38(s,3H).
13 C NMR(101MHz,CDCl 3 )δ202.0,139.3,136.8,130.4,128.8,127.8,127.6,127.4,126.4,55.1,42.7,18.2.
HRMS(ESI-FT-ICR)m/z:[M+Na] + Calcd for C 16 H 16 ONa 247.1093；Found:247.1099.
Comparative example 1
The reaction procedure and conditions were the same as those of example 1 except that the yield of the product of example 1 was 51% when the carbon monoxide gas pressure was changed to 3bar (gauge).
Comparative example 2
The reaction procedure and conditions were the same as those of example 1 except that the yield of the product of example 1 was 17% when the carbon monoxide gas pressure was 55bar (gauge).
Comparative example 3
The reaction procedure and conditions were the same as those of example 1 except that the reaction temperature was changed to 40℃and the yield of the product of example 1 was 36%.
Comparative example 4
The reaction procedure and conditions were the same as those of example 1 except that the reaction temperature was 130℃and the yield of the product of example 1 was 47%.
Comparative example 5
The reaction procedure and conditions were the same as those of example 1 except that the yield of the product of example 1 was 48% when the reaction time was changed to 5 hours; (short reaction time, incomplete reaction).
Comparative example 6
The reaction procedure and conditions were the same as those of example 1 except that the reaction time was 40 hours, and the yield of the product of example 1 was 42%. Comparative example 7 (decomposition of product over reaction time)
The reaction procedure and conditions were the same as those of example 1 except that the yield of the product of example 1 was 6% when the copper catalyst was changed to copper oxide.
Comparative example 8
The reaction procedure and conditions were the same as those of example 1 except that in the case where the alcohol was changed to methanol hexafluoroisopropanol, the yield of the product of example 1 was 19%.
Example 11
The reaction procedure and conditions were the same as in example 1, except that, when the olefin 1 was 1f, the reaction time was 20 hours, and the yield of the product 4f was 57%.
Example 12
The reaction procedure and conditions were the same as in example 1, except that, when the olefin 1 was 1j, the reaction temperature was 100℃and the yield of the product 4f was 48%.
Claims (9)
1. A process for preparing a β -boron substituted aldehyde derivative, characterized by:
the alkene 1, the diboron compound 2 and the carbon monoxide 3 shown in the following formula are used as raw materials to generate the beta-boron substituted aldehyde derivative 4, and the reaction formula is as follows:
the olefin 1 has the structure ofOr one or more of 1-methylene-1, 2,3, 4-tetrahydronaphthalene, 1-methyleneindane and 2-isopropylphenyl naphthalene, wherein R 1 The substituent on the benzene ring of the substituted phenyl comprises one to five, preferably 1 to 2, of methyl, tertiary butyl, methoxy, isopropyl, n-propyl, phenoxy and fluorine, and the number of the substituent is 1 to 5, preferably 1 to 2;
R 2 is one or two of C1-C5 alkyl chains (such as one or more of methyl, ethyl, isobutyl, cyclohexyl and n-butyl) and cyclopentylThe above.
2. A process for preparing a β -boron-substituted aldehyde derivative according to claim 1, wherein:
the specific operation steps are as follows:
firstly adding a catalyst, a ligand, alcohol, alkali, olefin 1, diboron compound 2 and a solvent into a reaction kettle, then replacing the atmosphere in the reaction kettle with carbon monoxide 3 gas, flushing 5-50bar (gauge pressure, preferably 5-10 bar) of carbon monoxide gas after replacement, and reacting at 50-120 ℃ (preferably 70-100 ℃), wherein the reaction time is 8-36 hours (preferably 20-24 hours); after the reaction, separating to obtain the beta-boron substituted aldehyde compound 4.
3. A method according to claim 2, characterized in that:
the catalyst is one or more than two of cuprous chloride, cupric acetate, cupric bromide and carbene copper complex, preferably cupric chloride; the catalyst is used in an amount of 1 to 10mol%, preferably 5 to 10mol%, based on the amount of olefin 1.
4. A method according to claim 2, characterized in that:
the ligand is one or more than two of triphenylphosphine, 1, 2-bis (diphenylphosphine) ethane, 1' -bis (diphenylphosphine) ferrocene, 4, 5-bis (diphenylphosphine) -9, 9-dimethyl xanthene, 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) -4, 5-dihydro-imidazole and 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) imidazole; preferably 2-methylene-1, 3-bis (2, 4, 6-trimethylphenyl) -4, 5-dihydro-imidazole; the amount of ligand is 1 to 10mol%, preferably 5 to 10mol%, based on the amount of olefin 1.
5. A method according to claim 2, characterized in that:
the alkali is one or more of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, potassium methoxide and sodium ethoxide, preferably potassium p-tert-butoxide; the amount of base is 100 to 400mol%, preferably 150 to 300mol%, based on the amount of olefin 1.
6. A method according to claim 2, characterized in that:
the alcohol is one or more of tert-butanol, methanol, ethanol and butanol, preferably p-tert-butanol; the amount of alcohol is 100 to 400mol%, preferably 150 to 250mol%, based on the amount of olefin 1.
7. A method according to claim 2, characterized in that:
the solvent is one or more of n-hexane, tetrahydrofuran, toluene, diethyl ether, methyl tert-butyl ether, 1, 4-dioxane and 1, 2-dichloroethane, preferably tetrahydrofuran; the solvent is used in an amount of 1.0 to 10.0 ml, preferably 5.0 to 8.0 ml, per millimole of olefin 1.
8. A method according to claim 2, characterized in that: the amount of diboron compound 3 (bispinacol borate, also known as bisglutaryl diboron, bis (pinacolato) diboron) is from 100 to 400mol%, preferably from 150 to 250mol%, based on the amount of aryl iodide.
9. A method according to claim 2, characterized in that: before the atmosphere replacement in the reaction kettle, the total loading amount of the catalyst, the ligand, the alcohol, the alkali, the olefin 1, the diboron compound 2 and the solvent in the reaction kettle is 50% or less than 50% of the volume of the reaction kettle.
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