CN105968137B - 一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 - Google Patents
一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 Download PDFInfo
- Publication number
- CN105968137B CN105968137B CN201610322585.8A CN201610322585A CN105968137B CN 105968137 B CN105968137 B CN 105968137B CN 201610322585 A CN201610322585 A CN 201610322585A CN 105968137 B CN105968137 B CN 105968137B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- compound shown
- aryl
- mol ratio
- 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.)
- Active
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 50
- -1 Biaryl monophosphorus Chemical compound 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 125000003118 aryl group Chemical group 0.000 claims abstract description 26
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000005859 coupling reaction Methods 0.000 claims abstract description 14
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 12
- 239000000126 substance Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 150000007530 organic bases Chemical class 0.000 claims description 32
- 239000003960 organic solvent Substances 0.000 claims description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 30
- 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 26
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000003107 substituted aryl group Chemical group 0.000 claims description 22
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 18
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 18
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 14
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- 229910021577 Iron(II) chloride Inorganic materials 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 13
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 13
- 230000035484 reaction time Effects 0.000 claims description 13
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 10
- 229910002666 PdCl2 Inorganic materials 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 9
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 239000003863 metallic catalyst Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052723 transition metal Inorganic materials 0.000 claims description 6
- 150000003624 transition metals Chemical class 0.000 claims description 6
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 5
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 claims description 5
- 239000005052 trichlorosilane Substances 0.000 claims description 5
- LDJXFZUGZASGIW-UHFFFAOYSA-L 2-diphenylphosphanylethyl(diphenyl)phosphane;palladium(2+);dichloride Chemical compound Cl[Pd]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 LDJXFZUGZASGIW-UHFFFAOYSA-L 0.000 claims description 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- XXECWTBMGGXMKP-UHFFFAOYSA-L dichloronickel;2-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 XXECWTBMGGXMKP-UHFFFAOYSA-L 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- AXYSDZQJEIAXBL-UHFFFAOYSA-N bis(oxomethylidene)iron Chemical compound O=C=[Fe]=C=O AXYSDZQJEIAXBL-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- SYTWXWRJCLAZFP-UHFFFAOYSA-L cobalt(2+);2-diphenylphosphanylethyl(diphenyl)phosphane;dichloride Chemical compound Cl[Co]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 SYTWXWRJCLAZFP-UHFFFAOYSA-L 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- ZXTCSIQSHINKKY-UHFFFAOYSA-L dichloroiron;2-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound Cl[Fe]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 ZXTCSIQSHINKKY-UHFFFAOYSA-L 0.000 claims description 3
- ZBQUMMFUJLOTQC-UHFFFAOYSA-N dichloronickel;3-diphenylphosphaniumylpropyl(diphenyl)phosphanium Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1[PH+](C=1C=CC=CC=1)CCC[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 ZBQUMMFUJLOTQC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- WLPXMKSDKMYLJS-UHFFFAOYSA-N CC#C[Si] Chemical compound CC#C[Si] WLPXMKSDKMYLJS-UHFFFAOYSA-N 0.000 claims 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical compound CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 150000003457 sulfones Chemical class 0.000 claims 1
- 150000002240 furans Chemical class 0.000 abstract description 3
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 abstract description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 239000000758 substrate Substances 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000006555 catalytic reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 9
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 8
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 8
- 239000004327 boric acid Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 229910052710 silicon Inorganic materials 0.000 description 8
- 239000010703 silicon Substances 0.000 description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 150000001499 aryl bromides Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000004679 31P NMR spectroscopy Methods 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 2
- 238000007259 addition reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 229940113088 dimethylacetamide Drugs 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 description 2
- 238000007115 1,4-cycloaddition reaction Methods 0.000 description 1
- IBSQPLPBRSHTTG-UHFFFAOYSA-N 1-chloro-2-methylbenzene Chemical compound CC1=CC=CC=C1Cl IBSQPLPBRSHTTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- 101100373011 Drosophila melanogaster wapl gene Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical class BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- NIDCLHUSBUORLB-UHFFFAOYSA-N Oc1ccc(cccc2)c2c1-c1c(cccc2)c2cc2c1[o]cc2 Chemical compound Oc1ccc(cccc2)c2c1-c1c(cccc2)c2cc2c1[o]cc2 NIDCLHUSBUORLB-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- RUIZXJNYLMYDLB-UHFFFAOYSA-N [P].C1=CC=CC=C1C1=CC=CC=C1 Chemical compound [P].C1=CC=CC=C1C1=CC=CC=C1 RUIZXJNYLMYDLB-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000007085 aza-Baylis-Hillman reaction Methods 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 230000001335 demethylating effect Effects 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 238000012938 design process Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000004483 pasc Anatomy 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
- B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
- B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
- B01J2231/4227—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group with Y= Cl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- C07C2531/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- C07C2531/24—Phosphines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用,该联芳基单膦配体是具有式(Ⅷ)所示化学结构式的化合物或它的对映体或消旋体。本发明的联芳基单膦配体通过引入呋喃环,与所属联萘形成共轭结构,增加了膦配体包括其对映体或消旋体的空间位阻及其芳香环的电子云密度,提高了配合物的稳定性,并调节配体的空间位阻,配体结构新颖,制备过程经过Sonogashira反应、分子内关环、C‑P偶联反应等,合成方法简单,所得配体应用于Suzuki‑Miyuara反应时具有活性高、选择性好等优点。
Description
技术领域
本发明属于化学催化领域,尤其涉及一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用。
背景技术
在催化反应中,底物与催化剂及配体的配位很重要,配体结构的微小改变常常会对催化反应的活性、选择性以及动力学等产生一系列影响。
磷原子基态的外层电子组态为3s23p3,它以不等性sp3杂化轨道与3个取代基(烷基、芳基或烷氧基、芳氧基)分别形成3个σ键。电子效应和立体效应是有机膦配体影响催化反应的两个重要方面,近年来在配体的设计过程中,一系列富电子、大位阻的膦配体相继问世,例如,1998年,Buchwald研究组开发了一系列富电子联苯单膦配体(StephenL.Buchwald,et al.J.Am.Chem.Soc.1998,120(37):9722-9723.),将其用于卤代芳烃的Suzuki偶联反应,能够高产率地得到偶联产物;2004年,他们又设计合成了一个高活性的联苯类单膦配体(Sphos)(Stephen L.Buchwald,et al.Angew.Chem.Int.Ed.2004,43(14):1871-1876.),能适用于多种类型的C-C偶联反应,如:Pd催化的Suzuki-Miyaura偶联反应(Stephen L.Buchwald,et al.J.Am.Chem.Soc.2005,127(13),4685–4696);Pd催化的Negishi偶联反应(Stephen L.Buchwald,et al.J.Am.Chem.Soc.2004,126(40),13028–13032),金催化的分子内炔烃与烯烃的[4+2]环加成(Antonio M.Echavarren,etal.J.Am.Chem.Soc.2005,127(17),6178–6179)以及二氢异香豆素类化合物的合成(HashmiA,Stephen K,et al.Aust.J.Chem.2014,67(3),481-499)等,并且都能较高活性的得到目标产物。2002年Stephen L.Buchwald等合成了一系列联萘结构的单膦配体,并将其用于酮烯醇的芳基化(Stephen L.Buchwald,et al.J.Am.Chem.Soc.2002,124(7),1261–1268);2007年,Fuk Yee Kwong等合成了一系列吲哚单膦配体,将其用于氯代芳烃的Suzuki偶联反应,只需要0.02%mol的钯,就能高活性的催化反应(Fuk Yee Kwong,etal.Org.Lett.2007,9(15),2795-2798);随后,2008年,该课题组又合成了一系列其它类型的吲哚类单膦配体(Fuk Yee Kwong,et al.J.Org.Chem.2008,73,7803–7806),将其用于氯代芳烃的Suzuki偶联反应,具有很高的活性;2010年Wenjun Tang等合成了一系列环化的单膦配体(Wenjun Tang,et al.Angew.Chem.Int.Ed.2010,49,5879–5883),并将其用于Pd催化的Suzuki-Miyaura偶联反应,能高活性的得到目标偶联产物。随后,又将配体进行拓展,并用于Miyaura硼化反应(Wenjun Tang,et al.Org.Lett.2011,13(6),1366–1369)和烯酰胺的不对称硼氢化(Wenjun Tang,et al.J.Am.Chem.Soc.2015,137(21),6746–6749)等,都可以得到很好的结果;2012年,Liqin Qiu等通过手性二醇的手性诱导,合成了一系列轴手性的联苯类单膦配体,并将其用于不对称Suzuki偶联,高选择性地得到目标偶联产物(Liqin Qiu,et al.Org.Lett.2012,14(8),1966–1969);2013年,该课题组又利用手性联萘单膦配体,经过不对称Suzuki偶联反应,高选择性的合成了含有功能基团醛基的轴手性化合物(Liqin Qiu,et al.Org.Lett.2013,15(21),5508–5511);2015年John A.Porco Jr等利用此类配体,首次合成了具有抗癌和抗菌作用的天然产物手性四氢氧杂蒽酮(JohnA.Porco Jr,et al.Nat.Chem.2015,7(3),234-240),均能得到较好的收率。
综上所述,通过前人的探索经验,膦配体在过渡金属催化反应中占有非常重要的位置,联芳基单膦配体在碳-碳键、碳-氧键和碳-氮键形成中有着广泛应用。尽管目前已经有不少单膦配体被报道,但由于底物和反应的多样性,对配体的要求也是多样性的,因此,急需研发不同类型结构的膦配体,从而满足不同反应类型的需要。
发明内容
本发明的目的是提供一类骨架新颖的含萘并呋喃结构的联芳基单膦配体。
本发明的另一个目的是提供上述联芳基单膦配体的制备方法。
本发明的另一个目的是提供上述联芳基单膦配体的应用。
本发明的上述目的是通过如下方案予以实现的:
一类含萘并呋喃结构的联芳基单膦配体,该联芳基单膦配体是具有式(Ⅷ)所示化学结构式的化合物或它的对映体或消旋体:
式中,
R1为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R2为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R3为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R4为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R5为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R6为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R7为氢、卤素、三甲基硅基、三乙基硅基、烷氧基、烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
R为烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种;
上述烷氧基为碳原子数为1-20的烷氧基;
上述烷基为碳原子数为1-20的烷基;
上述芳基为碳原子数为1-20的芳基;
上述环烷基为3-8元环的环烷基;
上述杂环基为含氧、硫、氮或磷原子的3-8元环的杂环基;
上述取代烷基、取代芳基、取代环烷基和取代杂环基中的取代是指含卤素、CF3、碳原子数为1-20的烷基或碳原子数为1-20的烷氧基中的任意一种或几种取代基。
当R1、R2、R3、R4、R5、R6和R7均为氢时,上述联芳基单膦配体的制备方法为:
步骤一.
式(1)所示化合物在有机溶剂中,在无机酸的存在下,脱去甲基甲醚基取代基得到式(2)所示化合物,反应温度为20℃~90℃,反应时间为2h~8h;所述有机溶剂的作用是提供反应环境,有机溶剂采用DMF(N,N-二甲基甲酰胺)、二氯甲烷、甲醇、乙醇、异丙醇或正丁醇中的任意一种;所述无机酸的作用是催化剂,无机酸的浓度为1mol/L~6mol/L,无机酸采用盐酸、硫酸或磷酸中的任意一种;式(1)所示化合物与无机酸的摩尔比为1:1~1:40;
步骤二.
式(2)所示化合物在有机溶剂中,在有机碱的存在下,与乙酸酐反应得到式(3)所示化合物,反应温度为20℃~50℃,反应时间为5h~24h;所述有机溶剂为三氯甲烷、二氯甲烷或四氢呋喃中的任意一种;所述有机碱为氮原子上含有孤对电子的有机碱,如三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;式(2)所示化合物与有机碱的摩尔比为1:1~1:4;式(2)所示化合物与乙酸酐的摩尔比为1:2~1:4;
步骤三.
式(3)所示化合物在有机溶剂中,在有机碱、碘化亚铜和金属催化剂的存在下,与三甲基乙炔基硅反应得到式(4)所示化合物,反应温度为0℃~50℃,反应时间为5h~48h;所述有机溶剂为三乙胺、三氯甲烷、二氯甲烷或四氢呋喃中的任意一种;所述有机碱为氮原子上含有孤对电子的有机碱,如三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种,所述金属催化剂为FeCl2(dppe)、FeCl2(PPh3)3、FeCl2(dppp)、FeCl2(dppb)、Fe(CO)2(PPh3)3、CoCl2(PPh3)3、CoCl2(dppe)、CoCl2(dppp)、CoCl2(dppb)、NiCl2(dppe)、NiCl2(dppp)、NiCl2(dppb)、PdCl2(dppe)、PdCl2(dppp)、PdCl2(dppb)、Pd(OAc)2(dppe)、Pd(OAc)2(dppp)、Pd(OAc)2(dppb)、PdCl2(PPh3)2或Pd2(dba)3中的任意一种;式(3)所示化合物与有机碱的摩尔比为1:1~1:4,式(3)所示化合物与碘化亚铜的摩尔比为1:0.01~1:0.5,式(3)所示化合物与金属催化剂的摩尔比为1:0.1~1:0.5,式(3)所示化合物与三甲基乙炔基硅的摩尔比为1:1~1:5;
步骤四.
式(4)所示化合物在有机溶剂中,在无机碱的存在下,温度25℃~100℃,反应4h~48h,先得到关环产物;该关环产物在有机溶剂中,与三溴化硼反应脱去萘环甲氧基上的甲基,得到式(5)所示化合物,反应温度为-78℃~25℃,反应时间为0.5h~12h;其中式(4)所示化合物在关环反应中使用的有机溶剂为DMSO(二甲基亚砜)、N,N-二甲基乙酰胺或N,N-二甲基甲酰胺中的任意一种;后一步脱去萘环甲氧基上的甲基的反应所用的有机溶剂为二氯甲烷、三氯甲烷或四氢呋喃中的任意一种;所述无机碱为氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、碳酸铯、磷酸钾或氢化钠中的任意一种;式(4)所示化合物与无机碱的摩尔比为1:1~1:6;所述关环产物与三溴化硼的摩尔比为1:1~1:4;
步骤五.
式(5)所示化合物在有机溶剂中,在有机碱存在的情况下,与三氟甲磺酸酐反应得到式(6)所示化合物反应温度为0℃~50℃,反应时间为2h~24h;所述三氟甲磺酸酐与式(5)所示化合物的摩尔比为1:1~1:4,式(5)所示化合物与有机碱的摩尔比位1:1~1:10;所述有机溶剂为二氯甲烷或三氯甲烷中的任意一种,所述有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;
步骤六.
在过渡金属与膦配体形成的配合物催化剂以及有机碱存在条件下,式(6)所示化合物与在有机溶剂中反应得到式(7)所示化合物,反应温度为50℃~120℃,反应时间为8h~48h;式(6)所示化合物与的摩尔比为1:1~1:5,式(6)所示化合物与过渡金属与膦配体形成的配合物催化剂的摩尔比为100:1~1:1,式(6)所示化合物与有机碱的摩尔比为1:1~1:10;所述过渡金属与膦配体形成的配合物催化剂为FeCl2(dppe)、FeCl2(PPh3)3、FeCl2(dppp)、FeCl2(dppb)、Fe(CO)2(PPh3)3、CoCl2(PPh3)3、CoCl2(dppe)、CoCl2(dppp)、CoCl2(dppb)、NiCl2(dppe)、NiCl2(dppp)、NiCl2(dppb)、PdCl2(dppe)、PdCl2(dppp)、PdCl2(dppb)、Pd(OAc)2(dppe)、Pd(OAc)2(dppp)、Pd(OAc)2(dppb)、PdCl2(PPh3)2或Pd2(dba)3中的任意一种;所述有机溶剂为甲苯、DMSO、N,N-二甲基乙酰胺或N,N-二甲基甲酰胺中的任意一种,所述有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;所述中R为烷基、芳基、环烷基、杂环基以及取代烷基、取代芳基、取代环烷基或取代杂环基中的任意一种,所述取代烷基、取代芳基、取代环烷基和取代杂环基中的取代是指含卤素、CF3、碳原子数为1-20的烷基或碳原子数为1-20的烷氧基中的任意一种或几种取代基。
步骤七.
式(7)所示化合物在有机溶剂中,在有机碱的存在下与三氯硅烷反应得到式(8)所示化合物,反应温度为50℃~140℃,反应时间为6h~48h;所述有机溶剂为甲苯、苯或二甲苯中的任意一种;所述有机碱为氮原子上含有孤对电子的有机碱,如三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;式(7)所示化合物与有机碱的摩尔比为1:2~1:30;式(7)所示化合物与三氯硅烷的摩尔比为1:2~1:30。
当R1、R2、R3、R4、R5、R6和R7为非氢原子时,其制备方法可选择本领域公认的合成方法,如在相应的后续步骤前通过丁基锂、溴素、NBS(N-溴代丁二酰亚胺)或NIS(N-碘代丁二酰亚胺)在式(1)所示化合物、式(2)所示化合物、式(3)所示化合物、式(4)所示化合物、式(5)所示化合物或式(6)所示化合物上先选择性引入卤素,再通过常规偶联反应或取代反应(G.Dyker,et al.Eur.J.Org.Chem.2008,3095-3101;S.Jiang,et al.Org.Lett.2011,13(16),4340–4343;X.Zheng,Z.Wang,et al.Eur.J.Org.Chem.2008,5112–5116)分别引入烷氧基、烷基、芳基、杂环基、环烷基、三甲基硅基、三乙基硅基以及取代烷基、取代芳基、取代环烷基或取代杂环基。
本发明的联芳基单膦配体包括其对映体或消旋体可用于钯、铑、镍、铜、铱、钌、钴、金、铂等多种金属催化的烯丙基化反应、不饱和酮脂的加成反应、烯烃还原加氢反应、席夫碱与烯烃的环加成Aza-Baylis-Hillman反应、醛酮与各种硼酸的加成反应或Suzuki-偶联反应中。
由上述方法所得的含磷中间体[如式(7)所示化合物]或不含磷的中间体[如式(2)所示化合物、式(3)所示化合物、式(4)所示化合物、式(5)所示化合物和式(6)所示化合物]等都可用于催化反应。
与现有技术相比,本发明具有如下有益效果:
本发明的联芳基单膦配体通过引入呋喃环,与所属联萘形成共轭结构,增加了膦配体包括其对映体或消旋体的空间位阻及其芳香环的电子云密度,提高了配合物的稳定性,并调节配体的空间位阻,配体结构新颖,制备过程经过Sonogashira反应、分子内关环、C-P偶联反应等,合成方法简单,所得配体应用于Suzuki-Miyuara反应时具有活性高、选择性好等优点。
具体实施方式
下面结合具体实施例对本发明做进一步地描述,但具体实施例并不对本发明做任何限定。
实施例1联芳基单膦配体
本实施例以式((+)-8A)所示联芳基单膦配体为例,介绍其制备过程。
(一)、用式((+)-1)所示化合物制备式((+)-2)所示化合物
在氮气保护下,将1.0g(2.13mmol)式((+)-1)所示化合物溶于50mL乙醇,加入10mL4mol/L的稀盐酸,80℃反应7h后减压旋干乙醇,然后加入100mL水溶解,用乙酸乙酯萃取3次,合并有机相,饱和食盐水洗,无水硫酸镁干燥,减压除去溶剂后粗产物经硅胶柱柱层析得到850mg产物式((+)-2)所示化合物,产率:93%,产物分析结果:[α]D 17+47.5(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.48(1H,s),8.10(1H,d,J=12.0Hz),7.93(1H,d,J=8.0Hz),7.80(1H,d,J=8.0Hz),7.52(1H,d,J=12.0Hz),7.38(1H,t,J=8.0Hz),7.34-7.31(2H,m),7.27-7.22(1H,m),7.15(1H,d,J=8.0Hz),7.05(1H,d,J=8.0Hz),5.41(1H,s),3.83(3H,s).13C NMR(101MHz,CDCl3)δ156.6,149.3,138.9,133.7,133.6,131.2,130.5,129.3,128.2,127.4,127.0,126.9,125.0,124.6,124.2,124.0,123.2,117.4,115.5,115.4,113.5,86.0,56.6.
(二)、用式((+)-2)所示化合物制备式((+)-3)所示化合物
将0.9g(2.11mmol)式((+)-2)所示化合物溶于20mL二氯甲烷,加入乙酸酐0.8mL(8.44mmol),吡啶0.7mL(8.44mmol),25℃搅拌24小时,然后加入1mol/L的盐酸30mL,乙酸乙酯萃取3次,合并有机相,饱和食盐水洗涤,无水硫酸镁干燥,减压蒸干有机相,得到的粗产品经硅胶柱柱层析得到950mg产物式((+)-3)所示化合物,产率:96%,产物分析结果:[α]D 17+76.9(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.54(1H,s),8.03(1H,d,J=8.0Hz),7.86(1H,t,J=12.0Hz),7.50-7.44(2H,m),7.38-7.30(3H,m),7.26(1H,t,J=8.0Hz),7.15(1H,d,J=8.0Hz),3.81(3H,s),1.80(3H,s).13C NMR(101MHz,CDCl3)δ167.9,154.8,146.5,139.0,130.4,127.7,127.0,126.7,126.3,125.3,123.8,117.3,113.4,90.3,56.7,20.6.
(三)、用式((+)-3)所示化合物制备式((+)-4)所示化合物
在氮气保护下,将1.5g(3.21mmol)式((+)-3)所示化合物溶于20mL无水三乙胺,加入CuI(6.1mg,0.0321mmol),PdCl2(PPh3)2(451mg,0.642mmol),三甲基乙炔基硅0.7mL(4.81mmol),反应液在室温下搅拌24h,减压蒸干溶剂,得到的粗产品经硅胶柱柱层析得到1.0g产物式((+)-4)所示化合物,产率:71%,产物分析结果:[α]D 17+92.9(c=0.1,CHCl3),1HNMR(400MHz,CDCl3)δ8.22(1H,s),8.02(1H,d,J=8.0Hz),7.89(2H,t,J=8.0Hz),7.49-7.41(2H,m),7.37-7.24(3H,m),7.21-7.15(2H,m),3.79(3H,s),1.87(3H,s),0.29(9H,s).13C NMR(101MHz,CDCl3)δ168.0,154.9,146.9,133.5,131.3,130.1,128.9,128.0,127.7,127.3,126.6,126.4,126.1,125.4,123.7,117.2,116.7,113.5,100.7,99.0,56.7,20.3,0.06.
(四)、用式((+)-4)所示化合物制备式((+)-5)所示化合物
将1.0g(2.28mmol)式((+)-4)所示化合物溶于50mL N,N-二甲基乙酰胺,加入5mL水,3.7g(11.4mmol)碳酸铯,混合液在氮气保护下于70℃搅拌2天,然后加入100mL水,乙酸乙酯萃取3次,合并有机相,饱和食盐水洗涤,有机相用无水硫酸镁干燥,得到的粗产物无需纯化直接用于下一步反应。在氮气保护下,将900mg(2.78mmol)粗产物溶于20mL无水二氯甲烷,当温度降至-78℃时,加入0.53mL(5.56mmol)三溴化硼,反应于-78℃反应30min,缓慢升温至0℃反应1h,在0℃下用冰水淬灭反应,二氯甲烷萃取,合并有机相,饱和食盐水洗涤,有机相用无水硫酸镁干燥,减压蒸干溶剂,粗产物经硅胶柱柱层析得到820mg产物式((+)-5)所示化合物,产率:95%,产物结果分析:[α]D 17+54.5(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.30(1H,s),8.12(1H,d,J=8.0Hz),8.02(1H,d,J=8.0Hz),7.94(1H,d,J=8.0Hz),7.67(1H,s),7.56-7.50(2H,m),7.44(1H,d,J=8.0Hz),7.40-7.35(2H,m),7.23(1H,t,J=4.0Hz),7.04-7.00(2H,m).13C NMR(101MHz,CDCl3)δ152.8,151.6,147.9,133.5,131.1,130.6,130.4,129.1,128.6,128.4,128.2,126.7,126.0,125.2,124.7,124.5,123.5,120.6,117.5,112.9,111.0,106.4.
(五)、用式((+)-5)所示化合物制备式((+)-6)所示化合物
在氮气保护下,将1.2g(3.87mmol)式((+)-5)所示化合物溶于30mL二氯甲烷,在0℃下加入1.4mL(7.74mmol)N,N-二异丙基乙胺,0℃搅拌30min后缓慢加入1.0mL(5.80mmol)三氟甲磺酸酐,加完后升至室温反应12h,然后加入30mL水淬灭反应,二氯甲烷萃取3次,合并有机相,饱和食盐水洗涤,无水硫酸镁干燥,减压蒸干溶剂,粗产物经硅胶柱柱层析的得到1.5g产物式((+)-6)所示化合物,产率:88%,产物结果分析:[α]D 17+81.5(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.31(1H,s),8.17(1H,d,J=8.0Hz),8.11(1H,d,J=8.0Hz),8.06(1H,d,J=8.0Hz),7.69-7.67(2H,m),7.62-7.58(1H,m),7.50-7.47(1H,m),7.39-7.34(4H,m),7.00(1H,m).13C NMR(101MHz,CDCl3)δ152.3,147.6,145.8,132.6,131.0,130.6,128.5,128.3,127.7,127.1,126.8,125.6,125.3,124.1,120.8,119.6,116.5,110.6,106.3.
(六)、用式((+)-6)所示化合物制备式((+)-7A)所示化合物
在氮气保护下,将600mg(1.36mmol)式((+)-6)所示化合物溶于15mL DMSO,加入329mg(1.63mmol)二苯基氧膦,0.9mL(5.43mmol)DIPEA(二异丙基乙胺),57.8mg(0.136mmol)Pd(OAc)2(dppb)((1,4-双二苯基膦丁烷)醋酸钯),升温至110℃,反应48h。反应结束后混合液倒入100mL水中,乙酸乙酯萃取3次,合并有机相,饱和食盐水洗涤,无水硫酸镁干燥,减压蒸干溶剂,粗产物经硅胶柱柱层析,得到550mg产物式((+)-7A)所示化合物,产率:82%,产物结果分析:[α]D 17+108.3(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.12(1H,d,J=8.0Hz),8.04-7.98(2H,m),7.88(1H,s),7.81(1H,d,J=8.0Hz),7.56(1H,t,J=8.0Hz),7.48-7.43(3H,m),7.38-7.30(2H,m),7.25-7.10(8H,m),7.03(1H,d,J=12.0Hz),6.94(1H,t,J=8.0Hz),6.76(1H,m).13C NMR(101MHz,CDCl3)δ152.0,147.0,138.1(d),134.9,133.2(d),133.1,132.7,132.2,131.7,131.5(d),131.1,131.0(d),130.9(d),130.6(d),130.5,130.1,129.1(d),128.5(d),128.1(d),127.8(d),127.6,127.4,127.2,127.1(d),127.0,126.1,124.9,123.7,120.2,115.3(d),106.1.31P NMR(162MHz,CDCl3)δ28.4.
(七)、用式((+)-7A)所示化合物制备式((+)-8A)所示化合物
在氮气保护下,将550mg(1.11mmol)式((+)-7A)所示化合物溶于20mL无水除氧甲苯,加入3.9mL(22.2mmol)N,N-二异丙基乙胺,降温至0℃,加入1.1mL(11.1mmol)三氯硅烷,升温至室温搅拌30min,然后加热升温至100℃反应12h。反应完毕后,将反应液降温至0℃,加入1mol/L的氢氧化钠溶液5mL,减压旋干溶剂,粗产物经硅胶柱柱层析,得到470mg产物式((+)-8A)所示化合物,产率:88%,产物结果分析:[α]D 17+89.5(c=0.1,CHCl3),1H NMR(400MHz,CDCl3)δ8.22(1H,s),8.06(1H,d,J=8.0Hz),7.98-7.94(2H,m),7.50-7.47(2H,m),7.41(1H,t,J=8.0Hz),7.34-7.23(7H,m),7.21-7.11(8H,m),6.86-6.85(1H,m).13C NMR(101MHz,CDCl3)δ147.4,133.7,133.6(d),133.4(d),130.4,130.1,128.6,128.2,128.1(d),128.0(d),127.6,126.8,126.6,126.5,125.8,124.9,124.7,123.8,113.4,106.0.31PNMR(162MHz,CDCl3)δ-12.9.
采用合成手性对映体相同的方法,用消旋体(±)-1替代手性纯化合物(+)-1,众所周知可以制备其相应的消旋体(±)-8A,除了无旋光性以外,合成(±)-8A的过程中所产生的其它中间体具有与合成化合物(+)-8A的过程中所得到的手性中间体相同的谱学表征数据。
为了考察联芳基单膦配体在偶联反应中的应用,我们将其用于Suzuki偶联反应,在底物的选择上,我们依次降低底物反应活性,分别进行了溴代芳烃与芳基硼酸或杂环芳基硼酸的偶联反应,氯代芳烃或杂环氯代芳烃与芳基硼酸的偶联反应,具体实施方法如实施例2、3、4、5所示。
实施例2:
在手套箱中,将Sm1(0.1mmol,1.0equiv)、Sm2(0.2mmol,2.0equiv),K3PO4(0.3mmol,3.0equiv),Pd2(dba)3(1.0%mmol),(±)-8A(2.0%mmol)和甲苯(4.0mL)置于25mL单口瓶中,在氮气保护下80℃搅拌反应1小时。产物结果分析:1H NMR(400MHz,CDCl3)δ8.05-8.01(3H,m),7.95(1H,d,J=8.0Hz),7.69(1H,t,J=4.0Hz),7.52-7.49(3H,m),7.40-7.23(5H,m),3.81(3H,s).13C NMR(101MHz,CDCl3)δ154.6,134.6,134.3,133.7,133.0,129.5,129.0,128.5,128.2,127.8,126.2,125.7,125.6,125.5,123.6,123.2,113.8,56.8.
实施例3:
在手套箱中,将Sm1(0.1mmol,1.0equiv)、Sm3(0.2mmol,2.0equiv),K3PO4(0.3mmol,3.0equiv),Pd2(dba)3(1.0%mmol),(±)-8A(2.0%mmol)和异丙醇(4.0mL)置于25mL单口瓶中,在氮气保护下80℃搅拌反应4小时。产物结果分析:1H NMR(400MHz,CDCl3)δ8.70-8.68(1H,m),8.66(1H,s),7.97(1H,d,J=12.0Hz),7.87(1H,t,J=4.0Hz),7.76-7.73(1H,m),7.50-7.45(2H,m),7.42-7.38(3H,m),3.87(3H,s).13C NMR(101MHz,CDCl3)δ154.1,151.8,148.2,138.6,133.3,130.0,128.9,128.1,126.8,124.5,123.7,123.1,133.3,56.5.
实施例4:
在手套箱中,将Sm4(0.1mmol,1.0equiv)、Sm2(0.2mmol,2.0equiv),K3PO4(0.3mmol,3.0equiv),Pd2(dba)3(1.0%mmol),(±)-8A(2.0%mmol)和甲苯(4.0mL)置于25mL单口瓶中,在氮气保护下80℃搅拌反应12小时。产物结果分析:1H NMR(400MHz,CDCl3)δ7.96(1H,d,J=8.0Hz),7.92(1H,d,J=8.0Hz),7.59(1H,t,J=8.0Hz),7.53-7.51(1H,m),7.39-7.38(2H,m),7.32-7.29(2H,m),7.23-7.21(2H,m),1.95(6H,s).13C NMR(101MHz,CDCl3)δ139.6,138.7,137.0,133.7,131.7,128.3,127.9,127.3,127.2,126.4,126.0,125.8,125.7,125.4,20.4.
实施例5:
在手套箱中,将Sm5(0.1mmol,1.0equiv)、Sm2(0.2mmol,2.0equiv),K3PO4(0.3mmol,3.0equiv),Pd2(dba)3(1.0%mmol),(±)-8A(2.0%mmol)和甲苯(4.0mL)置于25mL单口瓶中,在氮气保护下80℃搅拌反应8小时。产物结果分析:1H NMR(400MHz,CDCl3)δ8.96(1H,d,J=4.0Hz),7.99(2H,d,J=8.0Hz),7.62(1H,d,J=8.0Hz),7.57-7.47(3H,m),7.40-7.29(4H,m),7.06-7.03(1H,m),4.00(3H,s).13C NMR(101MHz,CDCl3)δ160.6,150.2,150.1,147.2,135.7,133.4,131.8,128.7,128.3,127.5,127.3,126.4,126.1,125.9,125.2,123.2,120.6,119.7,107.4,55.5.
在与实施例2、3、4和5相同的反应条件下,用Cy-MOP做为配体进行对比试验,其结果如表1所示;在与实施例2、3、4和5相同的反应条件下,分别改变膦配体,并测试它们的催化活性,其结果如表1所示;表1中,序号1-10为本发明的联芳基单膦配体,11为Cy-MOP的对比试验。
表1配体的性能测试试验结果
从表1可以看出,本发明的联芳基单膦配体对于卤代芳烃或杂环芳烃与芳基硼酸的Suzuki偶联反应具有很高的收率,其收率都高于Cy-MOP,这是由于呋喃环的引入,与所属联萘形成共轭结构,从而很好的调控了与Pd(0)形成的配合物的空间位阻,并且增加了氧原子的电子云密度,增加了与Pd(0)形成的配合物的稳定性,最终导致其反应收率要高于Cy-MOP。
实施例2为溴代芳烃与芳基硼酸的偶联反应,属于比较容易进行的偶联反应;实施例3为溴代芳烃与杂环芳基硼酸的偶联反应,反应难度比实施例2大一些;实施例4位2,6-二甲基氯苯与芳基硼酸的偶联反应,氯代芳烃的反应活性很低,另外两个邻位都有位阻,反应难度很大;实施例5为杂环氯代芳烃与芳基硼酸的偶联反应,但是由于位阻小,所以反应难度比实施例4小,但比溴代芳烃大;而本发明合成的配体及其催化体系对于不同底物的偶联反应,无论是对活性较好的溴代芳烃,还是活性较差的氯代芳烃,以及含有位阻的氯代芳烃,杂环氯代芳烃,尤其是对氯代芳烃的Suzuki偶联反应,均具有很好的催化活性和收率。
Claims (5)
1.一类含萘并呋喃结构的联芳基单膦配体,其特征在于所述联芳基单膦配体是具有式(Ⅷ)所示化学结构式的化合物
式中,
R1为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R2为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R3为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R4为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R5为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R6为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R7为氢、烷氧基、烷基、芳基、取代芳基中的任意一种;
R为烷基、芳基、环烷基、取代芳基、取代环烷基中的任意一种;
所述烷氧基为碳原子数为1-20的烷氧基;所述烷基为碳原子数为1-20的烷基;所述芳基为碳原子数为1-20的芳基;所述环烷基为3-8元环的环烷基;所述取代芳基和取代环烷基中的取代是指含CF3、碳原子数为1-20的烷基或碳原子数为1-20的烷氧基中的任意一种或几种取代基。
2.权利要求1所述的联芳基单膦配体的制备方法,其特征在于,R1、R2、R3、R4、R5、R6和R7为氢时,式(Ⅷ)所示化合物由如下方法制备而得:
步骤一.
式(1)所示化合物在有机溶剂中,在浓度为1mol/L~6mol/L的无机酸的存在下,脱去甲基甲醚基取代基得到式(2)所示化合物,反应温度为20℃~90℃,反应时间为2h~8h;
步骤二.
式(2)所示化合物在有机溶剂中,在有机碱的存在下,与乙酸酐反应得到式(3)所示化合物,反应温度为20℃~50℃,反应时间为5h~24h;
步骤三.
式(3)所示化合物在有机溶剂中,在有机碱、碘化亚铜和金属催化剂的存在下,与乙炔基三甲基硅反应得到式(4)所示化合物,反应温度为0℃~50℃,反应时间为5h~48h;
步骤四.
式(4)所示化合物在有机溶剂中,在无机碱的存在下,温度25℃~100℃,反应4h~48h,先得到关环产物;该关环产物在有机溶剂中,与三溴化硼反应脱去萘环甲氧基上的甲基,得到式(5)所示化合物,反应温度为-78℃~25℃,反应时间为0.5h~12h;
步骤五.
式(5)所示化合物在有机溶剂中,在有机碱存在的情况下,与三氟甲磺酸酐反应得到式(6)所示化合物反应温度为0℃~50℃,反应时间为2h~24h;
步骤六.
在过渡金属与膦配体形成的配合物催化剂以及有机碱存在的条件下,式(6)所示化合物与在有机溶剂中反应得到式(7)所示化合物,反应温度为50℃~120℃,反应时间为8h~48h;
步骤七.
式(7)所示化合物在有机溶剂中,在有机碱的存在下与三氯硅烷反应得到式(8)所示化合物,反应温度为50℃~140℃,反应时间为6h~48h;
当R1、R2、R3、R4、R5、R6和R7为非氢时,其制备方法为在进行相应的后续步骤之前,在式(1)所示化合物、式(2)所示化合物、式(3)所示化合物、式(4)所示化合物、式(5)所示化合物或式(6)所示化合物上先选择性引入卤素,再通过偶联反应或取代反应分别引入烷氧基、烷基、芳基或取代芳基。
3.根据权利要求2所述的联芳基单膦配体的制备方法,其特征在于所述步骤一中式(1)所示化合物与无机酸的摩尔比为1:1~1:40;所述步骤二中式(2)所示化合物与有机碱的摩尔比为1:1~1:4,式(2)所示化合物与乙酸酐的摩尔比为1:2~1:4;所述步骤三中式(3)所示化合物与有机碱的摩尔比为1:1~1:4,式(3)所示化合物与碘化亚铜的摩尔比为1:0.01~1:0.5,式(3)所示化合物与金属催化剂的摩尔比为1:0.1~1:0.5,式(3)所示化合物与三甲基乙炔基硅的摩尔比为1:1~1:5;所述步骤四中式(4)所示化合物与无机碱的摩尔比为1:1~1:6,关环产物与三溴化硼的摩尔比为1:1~1:4;所述步骤五中三氟甲磺酸酐与式(5)所示化合物的摩尔比为1:1~1:4,式(5)所示化合物与有机碱的摩尔比位1:1~1:10;所述步骤六中式(6)所示化合物与的摩尔比为1:1~1:5,式(6)所示化合物与过渡金属与膦配体形成的配合物催化剂的摩尔比为100:1~1:1,式(6)所示化合物与有机碱的摩尔比为1:1-1:10;所述步骤七中式(7)所示化合物与有机碱的摩尔比为1:2~1:30,式(7)所示化合物与三氯硅烷的摩尔比为1:2~1:30。
4.根据权利要求2所述的联芳基单膦配体的制备方法,其特征在于所述步骤一中有机溶剂为N,N-二甲基甲酰胺、二氯甲烷、甲醇、乙醇、异丙醇或正丁醇中的任意一种,无机酸为盐酸、硫酸或磷酸中的任意一种;所述步骤二中有机溶剂为三氯甲烷、二氯甲烷或四氢呋喃中的任意一种,有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;所述步骤三中有机溶剂为三乙胺、三氯甲烷、二氯甲烷或四氢呋喃中的任意一种,有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种,金属催化剂为FeCl2(dppe)、FeCl2(PPh3)3、FeCl2(dppp)、FeCl2(dppb)、Fe(CO)2(PPh3)3、CoCl2(PPh3)3、CoCl2(dppe)、CoCl2(dppp)、CoCl2(dppb)、NiCl2(dppe)、NiCl2(dppp)、NiCl2(dppb)、PdCl2(dppe)、PdCl2(dppp)、PdCl2(dppb)、Pd(OAc)2(dppe)、Pd(OAc)2(dppp)、Pd(OAc)2(dppb)、PdCl2(PPh3)2或Pd2(dba)3中的任意一种;所述步骤四中关环反应中使用的有机溶剂为二甲基亚砜、N,N-二甲基乙酰胺或N,N-二甲基甲酰胺中的任意一种,无机碱为氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、碳酸铯、磷酸钾或氢化钠中的任意一种,脱去萘环甲氧基上的甲基的反应所用的有机溶剂为二氯甲烷、三氯甲烷或四氢呋喃中的任意一种;所述步骤五中有机溶剂为二氯甲烷或三氯甲烷中的任意一种,有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;所述步骤六中过渡金属与膦配体形成的配合物催化剂为FeCl2(dppe)、FeCl2(PPh3)3、FeCl2(dppp)、FeCl2(dppb)、Fe(CO)2(PPh3)3、CoCl2(PPh3)3、CoCl2(dppe)、CoCl2(dppp)、CoCl2(dppb)、NiCl2(dppe)、NiCl2(dppp)、NiCl2(dppb)、PdCl2(dppe)、PdCl2(dppp)、PdCl2(dppb)、Pd(OAc)2(dppe)、Pd(OAc)2(dppp)、Pd(OAc)2(dppb)、PdCl2(PPh3)2或Pd2(dba)3中的任意一种,有机溶剂为甲苯、DMSO、N,N-二甲基乙酰胺或N,N-二甲基甲酰胺中的任意一种,有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种;所述步骤七中有机溶剂为甲苯、苯或二甲苯中的任意一种,有机碱为三乙胺、三甲胺、三丙胺、三丁胺、N,N-二异丙基乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶中的任意一种。
5.权利要求1所述联芳基单膦配体在金属催化的Suzuki偶联反应中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610322585.8A CN105968137B (zh) | 2016-05-15 | 2016-05-15 | 一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610322585.8A CN105968137B (zh) | 2016-05-15 | 2016-05-15 | 一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105968137A CN105968137A (zh) | 2016-09-28 |
CN105968137B true CN105968137B (zh) | 2018-04-06 |
Family
ID=56955844
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610322585.8A Active CN105968137B (zh) | 2016-05-15 | 2016-05-15 | 一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105968137B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106995461B (zh) * | 2017-03-03 | 2019-11-08 | 中山大学 | 一种含苯并呋喃结构的膦配体及其制备方法和应用 |
CN108259830B (zh) * | 2018-01-25 | 2019-08-23 | 深圳冠思大数据服务有限公司 | 基于云服务器的鼠患智能监控系统和方法 |
CN111018923B (zh) * | 2018-10-10 | 2024-04-19 | 东莞市均成高新材料有限公司 | 碳水化合物单膦、它们的制备方法和用途 |
WO2020077582A1 (en) * | 2018-10-18 | 2020-04-23 | Rhodia Operations | A process for preparing tertiary phosphines |
CN115368363B (zh) * | 2021-05-17 | 2024-02-20 | 中山大学 | 一种手性或消旋的嘧啶并二氮杂环庚酮类化合物及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102516300A (zh) * | 2011-11-09 | 2012-06-27 | 中山大学 | 一类膦配体及其对映体或消旋体及其制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7094725B2 (en) * | 2003-07-11 | 2006-08-22 | The Hong Kong Polytechnic University | Biphenyldiphosphine compounds |
-
2016
- 2016-05-15 CN CN201610322585.8A patent/CN105968137B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102516300A (zh) * | 2011-11-09 | 2012-06-27 | 中山大学 | 一类膦配体及其对映体或消旋体及其制备方法 |
Non-Patent Citations (1)
Title |
---|
"Enantioselective Synthesis of Axially Chiral Biaryl Monophosphine Oxides via Direct Asymmetric Suzuki Coupling and DFT Investigations of the Enantioselectivity";Yougui Zhou,et al.;《ACS Catal.》;20140407;第4卷;第1390−1397页 * |
Also Published As
Publication number | Publication date |
---|---|
CN105968137A (zh) | 2016-09-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105968137B (zh) | 一类含萘并呋喃结构的联芳基单膦配体及其制备方法和应用 | |
CN101952298B (zh) | 用于过渡金属催化的交联偶合反应的配体及其使用方法 | |
Xu et al. | Palladacycle-catalyzed phosphonation of aryl halides in neat water | |
Yang et al. | Nickel-catalyzed Arbuzov reactions of aryl triflates with triethyl phosphite | |
Guan et al. | Palladium-catalyzed oxalyl amide assisted direct ortho-alkynylation of arylalkylamine derivatives at δ and ε positions | |
Schmidt et al. | Pd‐Catalyzed [2+ 2+ 1] Coupling of Alkynes and Arenes: Phenol Diazonium Salts as Mechanistic Trapdoors | |
CN107501156A (zh) | 一种多取代吡咯的三组分串联合成方法 | |
Wu et al. | Palladium-catalyzed Suzuki–Miyaura couplings of potassium aryl trifluoroborates with 4-tosyloxycoumarins or 4-tosyloxyquinolin-2 (1H)-one | |
El Akkaoui et al. | Pd-catalyzed regiocontrolled Sonogashira and Suzuki cross-coupling reaction of 3, 6-dihalogenoimidazo [1, 2-a] pyridines: One-pot double-coupling approach | |
Zhang et al. | Palladium-catalyzed denitrogenative Hiyama cross-coupling with arylhydrazines under air | |
CN110078652A (zh) | 手性四芳基取代甲烷及其制备方法 | |
KR101067069B1 (ko) | 트리플루오로아세트산을 이용한 페난트리딘 유도체의 제조방법 | |
Iwasaki et al. | Synthesis of Multisubstituted Olefins through Regio‐and Stereoselective Addition of Interelement Compounds Having B–Si, B–B, and Cl–S Bonds to Alkynes, and Subsequent Cross‐Couplings | |
Pei et al. | Quinidine derived organocatalysts for the nucleophile promoted asymmetric [4+ 2] cycloaddition reaction of salicyl N-tosylimine with allenic esters | |
Dai et al. | Transition‐Metal‐Free Reaction of Aryltrimethylammonium Iodides with Arylzinc Reagents | |
Ruan et al. | Additive-free coupling of bromoalkynes with secondary phosphine oxides to generate alkynylphosphine oxides in acetic anhydride | |
Dou et al. | Palladium-catalyzed reductive Heck-type vinylative dearomatization of unfunctionalized halonaphthalene derivatives | |
Dabrowski et al. | An ortho‐lithiated derivative of protected phenylboronic acid: an approach to ortho‐functionalized arylboronic acids and 1, 3‐dihydro‐1‐hydroxybenzo [c][2, 1] oxaboroles | |
Sahnoun et al. | Cs2CO3 in pyrrolidinone promoted hydration of functionalized (hetero) aryl nitriles under metal-free conditions | |
Gagnon et al. | Csp³-Csp² Palladium-Catalyzed Cross-Coupling Reaction of Trialkylbismuth Reagents with Aryl, Heteroaryl, and Vinyl Halides and Triflates | |
Kanyiva et al. | Metal‐Free Aminoiodination of Alkynes Under Visible Light Irradiation for the Construction of a Nitrogen‐Containing Eight‐Membered Ring System | |
CN110003081A (zh) | 一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法 | |
CN102863391B (zh) | 含四-n-取代苯基苯并咪唑类化合物及其制备方法 | |
CN106995461A (zh) | 一种含苯并呋喃结构的膦配体及其制备方法和应用 | |
CN106674101A (zh) | 一种有机锑催化c‑h键官能团化构建喹啉化合物的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |