CN110240616A - 三联芳单膦配体、它们的制备方法和在催化偶联反应中的用途 - Google Patents
三联芳单膦配体、它们的制备方法和在催化偶联反应中的用途 Download PDFInfo
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- CN110240616A CN110240616A CN201810187687.2A CN201810187687A CN110240616A CN 110240616 A CN110240616 A CN 110240616A CN 201810187687 A CN201810187687 A CN 201810187687A CN 110240616 A CN110240616 A CN 110240616A
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- Prior art keywords
- phenyl
- bis
- phosphine
- mmol
- added
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Links
- -1 biaryl monophosphorus Chemical compound 0.000 title claims abstract description 182
- 239000003446 ligand Substances 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 10
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 114
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 69
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 67
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 35
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 8
- 150000003003 phosphines Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical group 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 239000000758 substrate Substances 0.000 claims abstract description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 154
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 84
- 238000006243 chemical reaction Methods 0.000 claims description 76
- 239000007818 Grignard reagent Substances 0.000 claims description 52
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 29
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical class ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 claims description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 150000005347 biaryls Chemical class 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 229910052723 transition metal Inorganic materials 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 150000003624 transition metals Chemical class 0.000 claims description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 5
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 230000007704 transition Effects 0.000 claims description 3
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000000958 aryl methylene group Chemical group 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 229910017052 cobalt Inorganic materials 0.000 claims description 2
- 239000010941 cobalt Substances 0.000 claims description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 2
- 230000000536 complexating effect Effects 0.000 claims description 2
- 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 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 238000005935 nucleophilic addition reaction Methods 0.000 claims 2
- MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 claims 1
- ZCJAYDKWZAWMPR-UHFFFAOYSA-N 1-chloro-2-fluorobenzene Chemical compound FC1=CC=CC=C1Cl ZCJAYDKWZAWMPR-UHFFFAOYSA-N 0.000 claims 1
- LGGHDPFKSSRQNS-UHFFFAOYSA-N Tariquidar Chemical compound C1=CC=CC2=CC(C(=O)NC3=CC(OC)=C(OC)C=C3C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CN=C21 LGGHDPFKSSRQNS-UHFFFAOYSA-N 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- RWGFKTVRMDUZSP-UHFFFAOYSA-N isopropyl-benzene Natural products CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 abstract description 9
- 238000006053 organic reaction Methods 0.000 abstract description 4
- 125000005841 biaryl group Chemical group 0.000 abstract 3
- 230000007812 deficiency Effects 0.000 abstract 1
- 150000002940 palladium Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 173
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 90
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- 239000003921 oil Substances 0.000 description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000012074 organic phase Substances 0.000 description 48
- 150000004795 grignard reagents Chemical class 0.000 description 47
- 238000001035 drying Methods 0.000 description 35
- 239000007787 solid Substances 0.000 description 35
- 238000010898 silica gel chromatography Methods 0.000 description 32
- 238000004679 31P NMR spectroscopy Methods 0.000 description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000003208 petroleum Substances 0.000 description 29
- 239000011777 magnesium Substances 0.000 description 27
- 229910052749 magnesium Inorganic materials 0.000 description 27
- 229940091250 magnesium supplement Drugs 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- 239000011734 sodium Substances 0.000 description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 22
- 235000011114 ammonium hydroxide Nutrition 0.000 description 22
- 239000000908 ammonium hydroxide Substances 0.000 description 21
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000004896 high resolution mass spectrometry Methods 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 239000012298 atmosphere Substances 0.000 description 16
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 14
- 229910052756 noble gas Inorganic materials 0.000 description 14
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 13
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000001119 stannous chloride Substances 0.000 description 13
- 235000011150 stannous chloride Nutrition 0.000 description 13
- 239000007832 Na2SO4 Substances 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- 230000003197 catalytic effect Effects 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 238000000605 extraction Methods 0.000 description 10
- 125000004437 phosphorous atom Chemical group 0.000 description 10
- 238000004817 gas chromatography Methods 0.000 description 9
- FUMMYHVKFAHQST-UHFFFAOYSA-N 2-bromo-1,3,5-tri(propan-2-yl)benzene Chemical compound CC(C)C1=CC(C(C)C)=C(Br)C(C(C)C)=C1 FUMMYHVKFAHQST-UHFFFAOYSA-N 0.000 description 8
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 206010015856 Extrasystoles Diseases 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 150000003613 toluenes Chemical class 0.000 description 5
- XNIGURFWNPLWJM-UHFFFAOYSA-N 1-bromo-2-methoxynaphthalene Chemical compound C1=CC=CC2=C(Br)C(OC)=CC=C21 XNIGURFWNPLWJM-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical compound Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical class [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- VHVYSMMZHORFKU-UHFFFAOYSA-N 2-bromo-1,3-dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1Br VHVYSMMZHORFKU-UHFFFAOYSA-N 0.000 description 3
- HVYCVAFNBSDPMP-UHFFFAOYSA-N 2-iodo-1,3-bis(2-methoxyphenyl)benzene Chemical compound COC1=CC=CC=C1C1=CC=CC(C=2C(=CC=CC=2)OC)=C1I HVYCVAFNBSDPMP-UHFFFAOYSA-N 0.000 description 3
- SRYLLIZURYSRBH-UHFFFAOYSA-N 2-iodo-5-methyl-1,3-diphenylbenzene Chemical compound IC=1C(C=2C=CC=CC=2)=CC(C)=CC=1C1=CC=CC=C1 SRYLLIZURYSRBH-UHFFFAOYSA-N 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- DGWFDTKFTGTOAF-UHFFFAOYSA-N P.Cl.Cl.Cl Chemical compound P.Cl.Cl.Cl DGWFDTKFTGTOAF-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- NMJASRUOIRRDSX-UHFFFAOYSA-N tert-butyl(dichloro)phosphane Chemical compound CC(C)(C)P(Cl)Cl NMJASRUOIRRDSX-UHFFFAOYSA-N 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- VZHJIJZEOCBKRA-UHFFFAOYSA-N 1-chloro-3-fluorobenzene Chemical group FC1=CC=CC(Cl)=C1 VZHJIJZEOCBKRA-UHFFFAOYSA-N 0.000 description 2
- FNJLLLMNTROXOC-UHFFFAOYSA-N 1-methyl-3,5-diphenylbenzene Chemical compound C=1C(C)=CC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 FNJLLLMNTROXOC-UHFFFAOYSA-N 0.000 description 2
- MYMYVYZLMUEVED-UHFFFAOYSA-N 2-bromo-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1Br MYMYVYZLMUEVED-UHFFFAOYSA-N 0.000 description 2
- NPDACUSDTOMAMK-UHFFFAOYSA-N 4-Chlorotoluene Chemical compound CC1=CC=C(Cl)C=C1 NPDACUSDTOMAMK-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 2
- 238000005577 Kumada cross-coupling reaction Methods 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- SJUKXVKSGSJVTJ-UHFFFAOYSA-M [Br-].[Mg+]C1CCCCC1 Chemical class [Br-].[Mg+]C1CCCCC1 SJUKXVKSGSJVTJ-UHFFFAOYSA-M 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
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Abstract
针对Buchwald等人发明的二联芳单膦(biaryl phosphine)配体存在的不足,本发明提供了间三联芳单膦配体,通式为Ia和Ib或它们的混合物,和它们的制备方法。本发明还描述了三联芳单膦配位的钯络合物。三联芳单膦配体与钯盐或络合物组成的体系、以及三联芳单膦配位的钯络合物在催化有机反应中的用途亦是本发明的一部分,特别是在催化涉及(拟)卤代芳烃为底物的偶联反应中的用途。
Description
技术领域
本发明涉及新颖的三联芳单膦配体(包括P-手性), 它们的制备方法, 它们作为关键组分和后过渡金属组成的催化体系, 以及它们在钯催化的有机反应特别是在催化偶联反应, 包括C-C和C-X键形成反应(X为N、O和F), 中的用途。
背景技术
多种有机反应可由过渡金属络合物高效催化实现, 因此在药物和有机材料的制备过程中常常见到过渡金属催化剂起到重要作用. 过渡金属催化剂的性能本质上取决于金属元素本身, 但能高效地实现丰富多样的有机转化, 包括不对称转化, 还有来自于其周边的配体的对金属中心性质调控的贡献. 其中, 有机配体, 尤其是膦配体, 对金属中心电子性质和金属中心周围立体环境的调控起到重要作用. 配位原子的σ给电子能力和π接受反馈电子能力调控了金属中心的电子性质以及影响了对位的配位原子与金属中心的配位强度, 配位原子的半径及其占据的周边尺寸影响到金属中心的配位数和其它配体(包括底物)的配位排布. 因此, 配体的电子性质与立体性质协同、综合地影响了催化反应的各个步骤, 对过渡金属能高效地催化有机转化起到了关键作用。
在过渡金属催化的许多有机反应中, 偶联反应是非常重要的一类反应. 因此,研发高效的手性或非手性膦配体以实现高效的催化偶联反应受到人们重视. 下式列出几类用于钯催化偶联反应而性能优异的富电子、大立***阻有机膦配体. Fu等人发现富电子、大立***阻的三特丁基膦在Pd催化的偶联反应中具有优异的性能, 掀起了开发这类新型膦配体的热潮(A. F. Littke, et al., J. Am. Chem. Soc.,2000, 122, 4020). 德国的Beller和耶鲁大学的Hartwig分别开发了富电子、大立***阻的二金刚基膦(M. Beller,et al., CN 101195641)和多取代苯基二茂铁膦QPhos (J. F. Hartwig, et al.,WO2002/011883), 都已成为商业化产品. 日本 Takasago公司研发出带芳基环丙基骨架的膦配体(cBRIDP) (K.Suzuki,et al,WO 2013/032035). 虽然Hiyashi等人早就发现了1,1’-二联萘-2-膦这类二联芳膦在钯催化的Kumada偶联反应中具有优越的催化性能, 但是Buchwald等人扩展了到二联苯膦, 又研发出一系列性能卓越的二联苯膦(S. L.Buchwald, et al., US6, 307, 087; WO 2009/076622). 除了富电子、大立***阻的特点外, 二联苯膦中的苯环B中的π电子还可以与钯中心产生弱配位作用, 这是二联芳膦配体具有卓越催化性能重要原因。
虽然Pd中心朝向苯环B, 并与芳基电子产生配位作用是能量最低的优势构象, 见下式, 但是还存在构象旋转导致Pd中心背向苯环B(T. E. Barder, et al., J. Am.Chem. Soc., 2007, 129, 5096). 而这类钯背向苯环B的物种的催化活性仅相当于二环己基苯基膦钯, 甚至, 可以形成Pd-C键而成为休眠催态物种. 这是这类二联芳膦存在的一个缺陷。
为了克服磷上的孤对电子或其配位的钯中心背向苯环B的这种构象而导致的缺陷. Buchwald等人又制备了在苯环A上引入甲基或甲氧基的二联芳膦, 见下式, 据称能有利于其配位的钯中心朝向苯环B的这种构象. 但引入的甲基或甲氧基, 由于它们与磷原子上的取代基之间的相互排斥作用或/和氧原子与钯中心的配位作用, 还是没能彻底弥补这个缺陷; 在实际催化过程中, 钯中心背向苯环B的这种构象可高达33% (B. P. Fors, D.A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc., 2008, 130, 13552-13554). 当然引入的甲基或甲氧基在防止钯与苯环A形成Pd-C键而阻止休眠态的形成上发挥了作用. Haddad等人利用氧亚甲基链固定构象使得孤对电子只能朝向苯环B, 而彻底解决了二联苯膦的这个构象可旋转的缺陷(WO 2011/126917). 这种通过氧亚甲基链固定构象的二联苯膦配体具有优越的催化性能, 但是存在合成步骤长达10步以上且需要用到多种昂贵的试剂的问题。
三联芳膦配体, 在磷原子的两边都有苯环, 使得磷原子上的孤对电子总有一个苯环B可以朝向, 则可以解决Buchwald等人的二联芳膦构象旋转的缺陷. 出于为了获得稳定的P=P双键物种的需要, B. Twamley等人制备了2,6-双(2,4,6-三异丙基苯基)苯基二氯化膦(B. Twamley, et al., J. Am. Chem. Soc., 1999, 121, 3357-3367). 出于研发光电材料的目的, 利用三联苯膦的大立***阻来稳定的P=P双键物种, K. Tsuji等人制备了带2,6-双(2,4,6-三甲基苯基)苯基磷骨架的化合物(K. Tsuji, et al., TetrahedronLett., 1999, 40, 3203). 2004年, Smith等人报道了一种三联芳膦, 2,6-双(2,4,6-三甲基苯基)苯基二甲膦(DmpPMe2, R. C. Smith, et al., Tetrahedron Letters, 2004,45, 8327-8330, 见下式), 在钯催化的Suzuki偶联反应中应用, 但由于磷原子上有2个立***阻较小的甲基基团, 这个三联芳膦的催化性能明显不如Buchwald的二联膦. Buster等人也制备出三联芳膦(B. Buster, et al., Inorganica Chimica Acta, 2009, 362,3465-3474),但磷原子上的另外2个取代基也都同时为甲基. Kondoh等人通过三炔烃在铑催化下成环的研究, 制备了几种三联芳膦(A. Kondoh, et al., J. Am. Chem. Soc.,2007, 129, 6996-6997, 见下式),包括8b-S配体, 同时发现8b-S在Buchwald-Hartwig偶联反应中具有较高的催化活性, 但这种膦配体的制备路线长、原料制备不易以及涉及到应用贵重的铑作为催化剂等问题, 另外磷原子边上是两个苯基不能避免形成Pd-C键休眠态物种的缺陷. 最近, Sasaki等人制备出双(2,4,6-三异丙基苯基)[4-溴-2,6-双(4-叔丁基苯基)苯基]膦 (S. Sasaki, et al.,Sulfur and Silicon, 2014, 189, 1207-1215), 其特征是磷原子对位是溴原子取代基, 也未见到用于组成过渡金属催化体系中. 饶等人公开了2,6-二苯基-1-溴苯与镁形成格氏试剂, 再在钯催化下与二苯基氯化膦或二特丁基氯化膦反应得到方法, 制备出(2,6-二苯基)-苯基二苯基膦配体和(2,6-二苯基)-苯基二特丁基膦配体(CN 105859774), 但未给出该化合物的任何结构鉴定或理化数据. 实际上,饶等人所要表述的是四(三苯基膦)钯在具有立***阻的格氏试剂与有大立***阻的一氯化膦反应中的作用。
2016年, Ortega-Moreno 等人分“2锅”制备了一系列三联苯二烷(炔)基膦(L.Ortega-Moreno, et al., Polyhedron, 2016, 116, 170-181. 见下式), 但磷原子上的另外2个取代基限于立***阻较小的基团:甲基、乙基、丙烯基、3-丁烯基或乙炔基. 也未开展催化方面的研究.
其中R = Me, R’ = H: R’’ = Me, Et, CH2CH=CH2, CH2CH2CH=CH2; R = Pri, R’= H:R’’ = Me, Et, CH2CH=CH2; R = R’ = Pri: R’’ = Me; R = R’ = Me: R’’ = 乙炔基。
本发明针对Buchwald等人的二联苯膦构象可扭转的缺陷而专门设计制备三联芳膦, 本发明的创造性还包括可以从价廉易得原料, 如间二氯苯, 特别是在磷原子引进大立***阻的取代基发明的, “一锅”地制备出多种新的三联芳膦. 另外, 两边的芳环上带杂原子(氧、氮)取代基三联芳膦, 如甲氧基、异丙氧基, 则未见到报道. 在制备磷原子上同时带2个叔丁基这种立***阻大的三联芳膦配体时, 本发明提供了分2步来进行的方法,也就是三联苯基负离子先与二氯叔丁基膦反应再与叔丁基负离子反应的过程, 这也是本发明得以制备带如叔丁基大立***阻取代基的三联芳膦的特征。
本发明研制的2,6-双(2,4,6-三异丙基苯基)苯基-二环己基膦(XTPhos)在钯催化的Suzuki-Miyaura偶联反应中的催化性能明显优于Smith等人研制的DmpPMe2的催化性能,另外在催化咔唑与4-氯甲苯的偶联反应中,性能优于Takasago公司的cBRIDP膦配体(其优于Buchwald的XPhos膦配体). 而本发明提供的2,6-双(2,4,6-三异丙基苯基)苯基-二环己基膦(ZTPhos)在钯催化的氯代芳烃的胺化反应中的性能明显优于Kondoh等人所研制的8b-S配体的催化性能. 本发明提供的更好的催化性能亦体现了本发明的创造性。
发明内容
第一方面, 本发明提供了三联芳单膦配体, 它们通式为Ia、Ib或它们的混合物,
其中, Ar 选自(C6-C20)芳基, 其可以有1到3个独立地选自(C1-C6)烷基、-O(C1-C6)烷氧基、-N(C1-C6)2二烷氨基或(C6-C10)芳基(这里的芳基同样可以有1到3个独立地选自(C1-C6)烷基、-O(C1-C6)烷氧基或-N(C1-C6)2二烷氨基的取代基)的取代基, 甚至Ar可以精选自苯基、4-甲基苯基、4-甲氧基苯基、4-异丙基苯基、4-叔丁基苯基、4-(二甲氨基)苯基、4-氟苯基、3,5-二甲基苯基、3,5-二叔丁基苯基、2-甲基苯基、2-甲氧基苯基、2-(二甲氨基)苯基、2-异丙基苯基、2,6-二甲基苯基、2,6-二异丙基苯基、2,6-二甲氧基苯基、2,6-二异丙氧基苯基、2,6-双(二甲氨基)苯基、2,6-二甲氧基-3,5-二苯基-苯基、2,6-二甲氧基-3,5-双(3,5-二甲基苯基)-苯基、2,6-二异丙氧基-3,5-二苯基-苯基、2,6-二甲氧基-3,5-双(2,4,6-三异丙基苯基)-苯基、2-甲氧基-6-(二甲氨基)苯基、2,4,6-三甲基苯基、2,4,6-三甲氧基苯基、2,4,6-三异丙基苯基、二茂铁基、1-萘基、2-萘基、2-甲氧基-1-萘基或9-蒽基的一种;
R1选自H、(C1-C6)烷基、-O(C1-C6)烷氧基或-N(C1-C6)2二烷基氨基, 甚至可精选自甲基、甲氧基、二甲氨基、异丙基或叔丁基中的一种;
R2和R3各自独立地选自(C1-C10)烷基、(C3-C10)环烷基、(5-11元)杂环烷基、(C6-C20)芳基、(C4-C20)杂芳基或-CH2(C6-C10)芳亚甲基, 这里的(C3-C10)环烷基、(5-11元)杂环烷基、(C6-C20)芳基、(C4-C20)杂芳基和-CH2(C6-C10)芳亚甲基中可以有1到3个独立地选自(C1-C6)烷基、-氧(C1-C6)烷氧基或-N(C1-C6)2二烷氨基的取代基, 这里的杂环烷基和杂芳基中的杂原子独立地选自选自O、N或S原子, 甚至R2和R3可以各自独立地精选自甲基、乙基、丙基、异丙基、正丁基、叔丁基、环戊基、环己基、金刚基、苯基、2-甲基苯基、2-异丙基苯基、2-甲氧基苯基、2-(二甲氨基)苯基、4-甲基苯基、4-氟苯基、4-甲氧基苯基、4-(二甲氨基)苯基、3,5-二甲基苯基、3,5-双(三氟甲基)苯基、3,5-二氟苯基、3,5-二叔丁基苯基、2,6-二甲基苯基、2,6-二甲氧基苯基、2,6-二异丙基苯基、2,4,6-三甲氧基苯基、2-联苯基、2’,6’-二甲基-2-联苯基、2’,6’-二甲氧基-2-联苯基、2’,6’-二异丙氧基-2-联苯基、2’,6’-双二甲氨基基-2-联苯基、2’,6’-二异丙基-2-联苯基、2’,4’,6’-三异丙基-2-联苯基、二茂铁基、2-呋喃基、2-噻吩基、2-苯并呋喃基、2-苯并噻吩基、2-吡啶基或2-四氢呋喃基;
当R1 = H且Ar = 苯基时, R2 或和R3不同时为叔丁基;
当R1 = H且当R2 = R3 = 甲基时, Ar不为2,6-二甲基苯基、2,6-二异丙基苯基、2,4,6-三甲基苯基或2,4,6-三异丙基苯基;
当R1 = H且当R2 = R3 = 乙基时, Ar不为2,6-二甲基苯基、2,4,6-三甲基苯基或2,6-二异丙基苯基。
第二方面, 本发明提供了上面描述的三联芳单膦配体(通式为Ia、Ib或它们的混合物)的制备方法. 其制备可以概括如下:带取代基R1或未带取代基的3,5-二氯苯或3-氟-5-氯苯在-100到-70oC下与丁基锂或仲丁基作用后, 再与ArMgX(X 可以是 Cl, Br或I)在-100到140oC温度范围内分阶段升温反应后, 然后, 可以选择再加入或不加入CuX1 (X1可以是 Cl, Br或I), 也可以选择再加入或不加入四(三苯基膦)钯, 根据加入氯化磷试剂的种类可选择在-100到30oC的温度范围内再加入PCl3、R2PCl2、R3PCl2或R2R3PCl反应, 再根据所加入的氯化磷试剂不同, 选择加入R2M和/或R3M (M = li, Na, MgX1, CuX1, 这里的X1可以是 Cl, Br或I). 本发明所提供的制备方法的特征之一是可以不需要分离提纯中间体“一锅”地实现制备三联芳单膦配体。
也可用2,6-二芳基苯基溴(碘)为原料(Mark C. Lipke, et al.,Organometallics, 2009, 28, 188-196), 通过通常被本领域所熟知的与正(仲或叔)丁基锂、金属镁或异丙基格式试剂反应制得2,6-二芳基苯基锂或镁试剂, 再与PCl3、R2PCl2、R3PCl2或R2R3PCl反应, 然后, 可以选择再加入或不加入CuX (X可以是 Cl, Br或I), 也可以选择再加入或不加入四(三苯基膦)钯, 再根据所加入的氯化磷试剂不同, 选择加入R2M和/或R3M (M = li, Na, MgX1或CuX1, 这里的 X1可以是 Cl, Br或I)。
第三方面,本发明提供的三联芳单膦配体所选自的取代基可以构成下面具体膦化合物:
(2,6-二苯基-4-甲基苯基)-二苯基膦;
(2,6-二苯基-4-甲基苯基)-二环己基膦;
(2,6-二苯基-4-甲基苯基)-二叔丁基膦;
[2,6-双(2-甲基苯基)苯基]-二苯基膦;
[2,6-双(2-甲基苯基)苯基]-二环己基膦;
[2,6-双(2-甲基苯基)苯基]-二叔丁基膦;
[2,6-双(2,6-二甲基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2,6-二甲基苯基)苯基]-叔丁基-2-呋喃基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-苯基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-环己基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-二苯基膦;
[2,6-双(2-甲氧基苯基)苯基]-二环己基膦;
[2,6-双(2-甲氧基苯基)苯基]-二叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2-甲氧基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-苯基-异丙基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-环己基-金刚基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二异丙氧基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二异丙氧基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-异丙基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲基-2-联苯基]-甲基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-甲基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二异丙基-2-联苯基]-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-二环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-苯基-环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-环己基-异丙基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲基-2-联苯基]- 正丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-甲基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二异丙基-2-联苯基]-叔丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-环己基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二苯基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二叔丁基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-(2-二甲氨基苯基)-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-(4-二甲氨基苯基)-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[2’,6’-二甲氧基-2-联苯基]-正丁基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[2’,6’-二异丙基-2-联苯基]-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-双[3,5-二(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[3,5-双(三氟甲基)苯基]-甲基膦;
[2,6-双(2-异丙氧基-1-萘基)苯基]-二苯基膦;
[2,6-双(2-异丙氧基-1-萘基)苯基]-二环己基膦;
[2,6-双(2-甲氧基-6-二甲氨基苯基)苯基]-二苯基膦;
[2,6-双(2-甲氧基-6-二甲氨基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲氨基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲氨基苯基)苯基]-二环己基膦。
第四方面, 本发明提供了三联芳单膦作为支持配体与元素周期表VIII族或IB族的元素, 例如钯、镍、铂、铑、铱、钌、钴或金的过渡金属络合物或过渡金属盐结合用作催化剂. 通常地, 本发明提供的三联芳单膦可以加入到合适的过渡金属前体中原位地产生催化体系.
第五方面, 本发明提供了一系列三联芳单膦配位的钯络合物, 具有通式II、III、IV、V、VI或VII:
其中,
L为上面定义的三联芳单膦配体;
X2为Cl、Br、I、甲磺酸基、苯磺酸基、对甲苯磺酸基、甲酸基、乙酸基或苯甲酸基;
R4、R5、R6、R7或R8各自独立地选自H、甲基或苯基.
本发明还进一步提供了原位产生的钯催化体系和钯络合物在催化Suzuki偶联和Buchwald-Hartwig胺化反应中的用途. 同时, 对于那些本领域技术人员来说很明显的其它过渡金属催化反应, 特别是Negishi偶联、Kumada偶联、Sonogashira炔化及Heck偶联,也可使用本发明提供的催化体系。
一般说来, 利用钯络合物作为催化剂的前体对于催化反应是更为有利的, 在一些情况中会缩短催化体系诱导期. 即使是直接应用钯络合物作为催化剂前体, 有时也额外相对钯来说加入0.5到100倍根据本发明的三联芳单膦配体, 这样一般会增加催化体系的寿命。
可以与本发明的膦配体原位形成催化剂的钯源有很多, 包括醋酸钯、氯化钯、乙酰丙酮钯、二苯基亚甲基丙酮钯、四(三苯基膦)钯、二乙腈氯化钯、2-氨基联苯-2-氯化钯,或其它对于那些本领域技术人员来说熟知的钯源。
本发明的膦配体在惰性气氛下有很好的热稳定性, 因此能在高达200oC或更高的温度下使用本发明提供的催化体系. 优选反应温度为20至180oC, 甚至是40至130oC进行催化反应是有利的. 本发明的三联芳单膦配体还可以再加压反应中使用, 通常压力可以到100个大气压, 但优选在不高于60的大气压到常压的范围进行反应。
本发明说明书中,THF表示四氢呋喃;TMEDA代表N,N,N’,N’-四甲基乙二胺。
格氏试剂的制备方法. 惰气气氛下, 往一个干燥的100 mL三口瓶中, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入镁屑. 将THF与溴带芳烃的混合液置于恒压漏斗中, 先加入约1 mL到三口瓶中, 反应引发后, 在保持微沸的情况下将剩余的混合液滴加到三口瓶中(约15 min), 加毕在油浴70℃下反应2-5 h, 冷却到室温备用。
以下举例说明本发明的具体实施例, 而不意味着本发明仅限于以下的举例说明。
实施例1. (2,6-二苯基-4-甲基-苯基)-二苯基膦。
。
实施例1-1。
由镁屑(0.29 g, 12.0 mmol)、THF (10 mL)与溴苯 (1.73 g, 11.0 mmol)的制得苯基溴化镁格氏试剂. 往另一个干燥的250 mL两口瓶中加入3,5-二氯甲苯(0.81 g, 5.0mmol)和THF (15 mL), 冷却到-78℃, 加入2.4 mL正丁基锂(2.5 M正己烷溶液, 6.0mmol), 搅拌反应30 min后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴70℃下回流6 h. 再冷却到-78℃, 通过注射器加入二苯基氯膦(1.32 g, 6.0mmol), 撤去冷浴升至室温反应6 h. 加入50 mL饱和氯化钠溶液, 用二氯甲烷萃取三次(40 mL), 有机层用Na2SO4干燥后减压浓缩, 残余物用硅胶柱层析分离提纯(石油醚洗脱),得白色固体1.39 g, 产率65%。
MP: 144.3-145.9℃。
1H NMR (400 MHz, CDCl3) δ: 7.14 (d, J = 2.7 Hz, 3H), 7.13 (s, 1H),7.12 – 7.07 (m, 10H), 7.06 (t, J = 4.3 Hz, 8H), 2.46 (s, 3H)。
13C NMR (101 MHz, CDCl3) δ: 150.29, 150.13, 143.10, 143.05, 138.80,137.65, 137.53, 132.45, 132.26, 131.70, 131.66, 129.24, 129.22, 127.65,127.59, 127.31, 127.00, 126.46, 21.12。
31P NMR (162 MHz, CDCl3)δ: -6.85。
HR-MS m/z (%): Calcd for C31H25P [M] 428.1688; Found 428.1671 (100)。
实施例1-2。
惰气气氛下, 往一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二苯基-4-甲基碘苯(0.74 g, 2.0 mmol), 加入THF (3.0 mL),冷却至-78℃, 通过恒压漏斗滴加0.89 mL正丁基锂(2.7 M正己烷溶液, 2.4 mmol)到反应液中(约8 min), 加毕后继续在此温度下反应2 h, 然后再通过注射器加入二苯基氯膦(0.44 g, 2.0 mmol), 撤去冷浴升至室温反应6 h. 加入20 mL饱和氯化钠溶液, 用二氯甲烷萃取三次(20 mL), 有机层用Na2SO4干燥后减压浓缩, 残余物用硅胶柱层析分离提纯(石油醚洗脱), 得白色固体0.60 g, 产率71%.。
实施例1-3。
由镁屑(0.06 g, 2.2 mmol)、THF (5 mL)和2,6-二苯基-4-甲基碘苯(0.74 g,2.0 mmol)制得格氏试剂. 冷却至-78℃, 通过注射器加入二苯基氯膦(0.49 g, 2.2mmol), 撤去冷浴升至室温反应6 h. 加入20 mL饱和氯化钠溶液, 用二氯甲烷萃取三次(20 mL), 有机层用Na2SO4干燥后减压浓缩, 残余物用硅胶柱层析分离提纯(石油醚洗脱),得白色固体0.59 g, 产率69%。
实施例2. (2,6-二苯基-4-甲基苯基)-二环己基膦。
。
惰气气氛下, 往一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二苯基-4-甲基碘苯(1.85 g, 5.0 mmol)和THF (10.0 mL), 冷却至-78℃, 通过恒压漏斗滴加2.04 mL正丁基锂(2.7 M正己烷溶液, 5.5 mmol)到反应液中(约8 min), 加毕后继续后继续反应2 h, 通过双针尖加入另一个史莱克瓶中的二环己基氯膦(1.16 g, 5.0 mmol)和THF (3.0 mL)的混合液, 撤去冷浴升至室温反应6 h, 加入20 mL饱和氯化钠溶液, 用二氯甲烷萃取三次(20 mL). 有机相用Na2SO4干燥后减压浓缩,残余物用硅胶柱层析分离提纯(石油醚), 得白色固体1.21 g, 产率55%。
MP: 138.3-139.6℃。
1H NMR (500 MHz, CDCl3) δ: 7.41 (s, 6H), 7.31 (s, 4H), 7.06 – 7.02 (m,2H), 2.39 (s, 3H), 1.31 (s, 22H)。
13C NMR (126 MHz, CDCl3) δ: 144.44, 144.40, 137.22, 131.20, 131.18,129.89, 129.87, 127.22, 126.61, 35.80, 35.69, 32.91, 32.71, 31.96, 31.53,31.45, 29.72, 29.68, 29.39, 27.06, 26.99, 26.97, 26.86, 26.26, 22.71, 20.90,14.13。
31P NMR (202 MHz, CDCl3) δ: -0.53。
HR-MS m/z (%): Calcd for C31H38P [M+ + H] 441.2705; Found 441.2734(100)。
实施例3. [2,6-双(2-甲基苯基)苯基]-二苯基膦。
。
惰气气氛下, 往一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二(2-甲基苯基)碘苯(1.54 g, 4.0 mmol)和THF (5.0 mL), 冷却至-78℃, 通过恒压漏斗滴加6.8 mL叔丁基锂(1.3 M正戊烷溶液, 8.8 mmol)到反应液中(约20 min), 加毕后继续反应2 h, 回至室温待用. 另一个干燥的100 mL两口瓶中加入氯化亚铜(0.48 g, 4.8 mmol), 通过双针尖加入上述待用的锂试剂, 加毕后继续搅拌20min后再冷却到-78℃, 通过注射器加入二苯基氯膦(0.88 g, 4.0 mmol), 撤去冷浴回至室温反应6 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50mL), 有机层用50 mL饱和氯化钠溶液洗涤, 再用二氯甲烷萃取氯化钠洗涤液三次(30mL), 合并的有机层用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体0.91 g, 产率52%。
MP: 146.5-147.3℃。
1H NMR (400 MHz, CDCl3) δ: 7.49 (dd, J = 14.6, 7.0 Hz, 1H), 7.22 –6.70 (m, 20H), 1.92 (d, J = 30.1 Hz, 6H)。
13C NMR (101 MHz, CDCl3) δ: 149.02, 148.85, 142.06, 135.30, 132.86,132.66, 130.33, 130.29, 129.48, 129.24, 129.22, 129.10, 127.42, 127.35,127.22, 127.06, 124.55, 20.82, 1.05。
31P NMR (162 MHz, CDCl3) δ: -5.37, -7.65。
HR-MS m/z (%): Calcd for C32H28P [M+ + H] 443.1923; Found 443.1903(100)。
实施例4. [2,6-双(2,6-二甲基苯基)苯基]-二苯基膦。
。
实施例4-1。
由镁屑(0.61 g, 25.0 mmol)、THF (10 mL)与2,6-二甲基溴苯(4.44 g, 24.0mmol)制得格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应1 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴80℃下回流6 h. 冷至室温后将反应液转移到一个装有氯化亚铜(1.20 g, 12.0mmol)的250 mL两口瓶中, 搅拌20 min后冷却到-78℃, 通过注射器加入二苯基氯膦(2.64g, 12 mmol), 升至室温继续反应6 h. 加入50 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相用50 mL饱和氯化钠溶液洗涤, 再用二氯甲烷萃取氯化钠洗涤液三次(30 mL), 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体2.91 g, 产率62%。
MP: 149.5-150.9℃。
1H NMR (400 MHz, CDCl3) δ: 7.51 (t, J = 7.6 Hz, 1H), 7.16 – 7.06 (m,8H), 7.05 – 6.99 (m, 4H), 6.99 – 6.92 (m, 2H), 6.82 (d, J = 7.6 Hz, 4H), 2.05(s, 12H)。
13C NMR (101 MHz, CDCl3) δ: 147.15, 147.00, 141.32, 141.28, 136.72,136.60, 136.00, 135.99, 134.71, 134.48, 130.39, 130.36, 129.16, 127.92,127.32, 127.23, 127.18, 21.55, 21.52。
31P NMR (162 MHz, CDCl3) δ: -2.18。
HR-MS m/z (%): Calcd for C34H32P [M+ + H] 471.2251; Found 471.2239(100)。
实施例4-2。
惰气气氛下, 往一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-双(2,6-二甲基苯基)碘苯(1.24 g, 3.0 mmol)和THF (5.0 mL),冷却至-78℃, 通过恒压漏斗滴加5.1 mL叔丁基锂(1.3M正戊烷, 6.6mmol)到反应液中(约20 min), 加毕后继续反应30 min, 撤去冷浴回至室温待用. 另一个干燥的100 mL两口瓶中加入氯化亚铜(0.48 g, 4.8 mmol), 通过双针尖加入上述待用的锂试剂, 加毕后搅拌20 min再冷到-78℃, 通过注射器加入二苯基氯膦(0.99 g, 4.5mmol), 升至室温继续反应6 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相用50 mL饱和氯化钠溶液洗涤, 再用二氯甲烷萃取氯化钠洗涤液三次(30 mL),合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体0.90g, 产率64%。
实施例5. [2,6-双(2,6-二甲基苯基)苯基]-环己基-噻吩基膦。
。
由镁屑(0.61 g, 25.0 mmol)、THF (10 mL)与2,6-二甲基溴苯(4.44 g, 24.0mmol)制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应1 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴80℃下回流6 h. 冷至室温后将反应液转移到一个装有氯化亚铜(1.20 g, 12.0mmol)的250 mL两口瓶中, 搅拌20 min后冷却到-78℃, 加入二氯环己基膦(2.22 g, 12.0mmol)和THF (5 mL)的混合液, 升至室温再于油浴40℃下回流6 h. 冷却至-80℃, 加入2-噻吩基溴化镁格式试剂 (36.0 mmol), 油浴70 ℃反应12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.45 g, 产率48%。
MP: 149.9-151.6℃。
1H NMR (400 MHz, CDCl3) δ: 7.60 – 7.52 (m, 1H), 7.49 – 7.44 (m, 1H),7.40 – 7.32 (m, 2H), 7.31 – 7.25 (m, 2H), 7.12 – 6.99 (m, 4H), 6.85 – 6.78(m, 1H), 6.02 – 5.94 (m, 1H), 2.42 – 2.27 (m, 1H), 2.20 (s, 6H), 1.81 – 1.74(m, 1H), 1.69 (s, 6H), 1.66 – 1.58 (m, 3H), 1.56 – 1.46 (m, 2H), 1.38 – 1.29(m, 1H), 1.27 – 1.18 (m, 1H), 1.15 – 1.00 (m, 2H)。
13C NMR (101 MHz, CDCl3) δ: 148.63, 148.49, 139.81, 139.74, 137.22,136.47, 136.43, 134.82, 132.62, 132.55, 131.87, 131.85, 131.18, 131.11,128.99, 128.58, 128.49, 128.19, 128.11, 127.54, 127.17, 126.90, 126.56,34.87, 34.58, 31.67, 31.57, 30.21, 30.13, 26.39, 26.23, 26.19, 26.03, 25.45,21.50, 20.76。
31P NMR (162 MHz, CDCl3) δ: -13.70。
实施例6. [2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲基氨基苯基]-苯基膦。
。
由镁屑(0.61 g, 25.0 mmol)、THF (10 mL)与2,4,6-三甲基溴苯(4.78 g, 24.0mmol)制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应1 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴80 ℃下回流6 h. 冷至室温后将反应液转移到一个装有氯化亚铜(1.20 g, 12.0mmol)的250 mL两口瓶中, 搅拌20 min后冷却到-78 ℃, 加入二氯苯基基膦(2.15 g,12.0 mmol)和THF (5 mL)的混合液, 升至室温再于油浴40℃下回流6 h. 冷却至-80℃,加入2-二甲氨基苯基溴化镁格式试剂(30.0 mmol), 油浴70℃反应12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体3.08 g, 产率57%。
MP: 151.2-152.9℃。
1H NMR (400 MHz, CDCl3) δ:7.62 – 7.47 (m, 2H), 7.46 – 7.30 (m,2H),7.26 – 7.17 (m, 2H), 7.09 – 6.96 (m, 4H), 6.94 – 6.86 (m, 2H), 6.85 – 6.75(m, 2H), 6.39 – 6.24 (m, 2H), 2.39 (s, 9H), 2.16 (s, 9H), 1.51 (s, 6H)。
31P NMR (162 MHz, CDCl3) δ: -19.14 (s)。
HR-MS m/z (%): Calcd for C38H41NP [M+ + H] 542.2971; Found 542.2975(100)。
实施例7. [2,6-双(2-甲氧基苯基)苯基]-二苯基膦。
。
惰气气氛下, 往一个干燥的100 mL 三口瓶中, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二(2-甲氧基苯基)碘苯(0.83 g, 2.0 mmol)和THF (5 mL),冷却至-78℃, 通过恒压漏斗滴加3.4 mL叔丁基锂(1.3M正戊烷, 4.4 mmol)到反应液中(约15 min), 加毕后继续反应1h, 仍在-78℃下通过注射器加入二苯基氯膦(0.44 g, 2.0mmol), 撤去冷浴自然升至室温再反应6 h. 加入15 mL饱和氯化钠溶液, 用二氯甲烷萃取三次(每次30 mL), 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 20:1), 得白色固体0.76 g, 产率80%。
MP: 144.6-146.1℃。
1H NMR (500 MHz, CDCl3) δ: 7.50 – 7.44 (m, 1H), 7.25 – 7.17 (m, 3H),7.15 – 7.13 (m, 1H), 7.11 – 6.96 (m, 12H), 6.91 – 6.85 (m, 2H), 6.74 – 6.63(m, 2H), 6.52 – 6.46 (m, 2H), 3.59 (s, 3H), 3.38 (s, 3H)。
13C NMR (126 MHz, CDCl3) δ: 156.48, 155.81, 145.99, 145.86, 145.72,145.60, 133.09, 132.98, 132.92, 132.83, 132.59, 132.43, 131.72, 131.68,131.65, 131.25, 131.24, 131.08, 131.05, 130.98, 130.95, 130.87, 130.85,128.46, 128.30, 127.25, 127.20, 127.17, 127.12, 126.94, 126.88, 126.78,126.65, 126.58, 119.37, 109.89, 109.71, 54.65, 54.46。
31P NMR (162 MHz, CDCl3) δ: -3.40, -5.52。
HR-MS m/z (%): Calcd for C32H28O2P [M+ + H] 475.1821; Found 475.1856(100)。
实施例8. [2,6-双(2-甲氧基苯基)苯基]-二环己基膦(HTPhos)。
。
惰气气氛下, 一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二(2-甲氧基苯基)碘苯(0.83 g, 2.0 mmol)和THF (5 mL), 冷却至-78℃, 通过恒压漏斗滴加3.4 mL叔丁基锂(1.3M正戊烷, 4.4 mmol)到反应液中(约15min), 加毕后继续反应1h, 仍在此温度下通过双针尖加入二环己基氯膦(0.47 g, 2.0mmol)和THF (3.0 mL)的混合液,撤去冷浴自然升至室温再反应6h. 加入15 mL饱和氯化钠溶液, 用二氯甲烷萃取三次, 每次30 mL, 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 20:1), 得白色固体0.76 g, 产率78%。
MP: 143.2-145.1℃。
1H NMR (500 MHz, CDCl3) δ: 7.37 – 7.31 (m, 3H), 7.17 – 7.06 (m, 4H),7.00 – 6.95 (m, 2H), 6.94 – 6.90 (m, 2H), 3.75 (s, 6H), 1.63 – 1.58 (m, 2H),1.55 – 1.46 (m, 6H), 1.46 – 1.35 (m, 3H), 1.12 – 1.00 (m, 5H), 0.97 – 0.91(m, 3H), 0.87 – 0.79 (m, 3H)。
31P NMR (202 MHz, CDCl3) δ: 5.75, 5.24。
HR-MS m/z (%): Calcd for C32H40O2P [M+ + H] 487.2760; Found 487.2762(100)。
实施例9. [2,6-双(2-甲氧基苯基)苯基]-二叔丁基膦。
。
惰气气氛下, 一个干燥的100 mL 三口瓶, 加入搅拌子, 装上冷凝管、恒压漏斗和抽气接头, 加入2,6-二(2-甲氧基苯基)碘苯(0.83 g, 2.0 mmol)和THF (5 mL), 冷却至-78℃, 通过恒压漏斗滴加3.4 mL叔丁基锂(1.3M正戊烷, 4.4 mmol)到反应液中(约15min), 加毕后继续反应1h, 仍在此温度下通过双针尖加入二氯叔丁基膦(0.32 g, 2.0mmol)和THF (3.0 mL)的混合液, 撤去冷浴自然升至室温再反应6h. 再加入CuCl(0.25 g,2.5 mmol)和2.2 mL叔丁基锂(1.3M正戊烷, 2.9 mmol)搅拌反应1 h后, 再回流反应24 h.冷至室温加入15 mL饱和氯化钠溶液, 用二氯甲烷萃取三次, 每次30 mL, 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 20:1), 得白色固体0.27 g, 产率31%。
31P NMR (162 MHz, CDCl3)δ: 23.69。
实施例10. [2,6-双(2,6-二甲氧基苯基)苯基]-二苯基膦。
。
实施例10-1。
由镁屑(0.29 g, 12 mmol)、THF (10.0 mL)与2,6-二甲氧基溴苯(2.39 g, 11.0mmol)制成格氏试剂. 另一个干燥的250 mL两口瓶中加入3-氯氟苯(1.47 g, 5.0 mmol)和THF (15 mL), 冷却到-78℃, 加入2.4 mL正丁基锂(2.5 M正己烷溶液, 6.0 mmol), 搅拌反应1 h后, 将上述制备格式试剂通过双针尖转移至两口瓶中, 撤去冷浴自然升至室温,再于油浴80℃下回流6 h. 冷至室温后将反应液转移到一个装有氯化亚铜(0.60 g, 6.0mmol)的250 mL两口瓶中, 搅拌20 min后冷却到-78℃, 通过注射器加入二苯基氯膦(1.32g, 6.0 mmol), 加毕油浴加热至70℃反应3 h. 室温下加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 合并的有机相再用50 mL饱和氯化钠溶液洗涤,水相再用二氯甲烷萃取三次(30 mL), 有机层用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯= 10:1), 得白色固体1.15 g, 产率43%。
MP: 154.2-156.2℃。
1H NMR (400 MHz, CDCl3) δ: 7.52 (dd, J = 10.6, 4.5 Hz, 1H), 7.16 –6.85 (m, 14H), 6.29 – 6.13 (m, 4H), 3.53 (d, J = 1.5 Hz, 12H)。
13C NMR (101 MHz, CDCl3) δ: 157.42, 141.41, 141.24, 137.46, 137.33,135.37, 135.17, 133.96, 133.75, 131.34, 128.79, 128.57, 126.77, 126.70,119.92, 119.86, 103.08, 55.12。
31P NMR (162 MHz, CDCl3) δ: -2.99。
HR-MS m/z (%): Calcd for C34H32O4P [M+ + H] 535.2032; Found 535.2029(100)。
实施例10-2.
由镁屑(0.67 g, 27.5 mmol)、THF (10.0 mL)与2,6-二甲氧基溴苯(5.40 g, 25.0mmol)制成格氏试剂. 另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0 mmol)和THF (15 mL), 冷却到-78℃, 加入5.0 mL正丁基锂(2.4 M正己烷溶液, 12.0 mmol),搅拌反应1 h后, 将上述制备格式试剂通过双针尖转移至两口瓶中, 撤去冷浴自然升至室温, 再于油浴70℃下回流6 h. 冷至室温, 通过双针尖加入四三苯基膦钯(0.17 g, 0.15mmol)与THF (5 mL)的溶液, 搅拌反应2 h. 通过注射器加入二苯基氯膦(3.3 g, 15.0mmol), 加毕油浴加热至70℃反应3 h. 室温下加入40 mL氨水(26.0%-28.0%)并搅拌30min, 用二氯甲烷萃取三次(50 mL), 合并的有机相再用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(30 mL), 有机层用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.56 g, 产率48%。
实施例11. [2,6-双(2,6-二甲氧基苯基)苯基]-苯基异丙基膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,6-二甲氧基碘苯(5.81 g,22.0 mmol)制成格氏试剂. 另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 滴加4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应2 h后, 通过双针尖加入上述待用的格式试剂, 升至室温, 再于油浴70℃下回流12 h后, 冷至室温, 再转移至另一个冷至-78℃的含有溴化亚铜(1.72 g, 12.0mmol)的100 mL两口瓶中, 加毕继续搅拌20 min后. 通过注射器加入二氯苯基膦(2.15 g,12.0 mmol), 加毕升至室温再反应12 h. 再冷却到-78℃, 通过注射器加入4.0 mL异丙基溴化镁(3.0 M的THF溶液, 12.0 mmol), 加毕升至室温反应12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 合并的有机相用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL), 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 20:1), 得白色固体2.90 g, 产率58%。
MP: 153.2-154.9℃。
1H NMR (400 MHz, CDCl3) δ: 7.47 (t, J = 7.5 Hz, 1H), 7.34 (ddd, J =18.9, 13.8, 6.7 Hz, 4H), 7.18 (d, J = 7.4 Hz, 3H), 6.70 (d, J = 8.3 Hz, 6H),3.80 (s, 12H), 3.77 (s, 6H), 1.82 (s, 1H)。
13C NMR (101 MHz, CDCl3) δ: 157.90, 157.68, 141.00, 136.99, 134.01,129.75, 129.31, 129.22, 128.44, 127.52, 124.60, 123.87, 120.04, 109.60,104.45, 104.32, 56.15, 55.96, 16.88。
31P NMR (162 MHz, CDCl3) δ: -13.29。
实施例12. [2,6-双(2,4,6-三异丙基苯基)苯基]-二苯基膦。
。
由镁屑(0.67 g,27.5 mmol)、THF (10 mL)与2,4,6-三异丙基溴苯(7.08 g, 25.0mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 滴加5.0 mL正丁基锂(2.4 M正己烷溶液, 12.0mmol), 搅拌反应1 h后, 仍在此温度下通过双针尖加入上述待用的格式试剂, 升至室温,再于油浴80℃下回流6 h. 冷却至室温将反应液转移到另一个250 mL带有溴化亚铜(2.15g, 15.0 mmol)两口瓶中, 搅拌反应15 min后冷却到-78℃, 通过注射器加入二苯基氯膦(3.31 g, 15.0 mmol), 加毕升至室温反应6 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30min, 用二氯甲烷萃取三次(50 mL), 合并的有机相用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL), 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体5.53 g, 产率83%。
MP: 148.4-149.6℃。
1H NMR (400 MHz, CDCl3)δ: 7.42 (t, J = 7.5 Hz, 1H), 7.20 (dd, J = 7.5,2.2 Hz, 2H), 7.00 (t, J = 6.9 Hz, 2H), 6.96 – 6.83 (m, 8H), 6.78 (s, 4H),2.89 – 2.77 (m, 6H), 1.26 (d, J = 6.9 Hz, 12H), 0.91 (dd, J = 34.9, 6.7 Hz,24H)。
13C NMR (101 MHz, CDCl3) δ: 147.48, 147.26, 145.84, 138.05, 137.91,137.27, 137.22, 134.65, 134.43, 132.29, 132.26, 127.64, 127.35, 127.31,127.28, 120.51, 34.03, 30.91, 25.59, 24.03, 22.61.
31P NMR (162 MHz, CDCl3) δ: -5.89。
HR-MS m/z (%): Calcd for C48H60P [M+ + H] 667.4427; Found 667.4479(100)。
实施例13. [2,6-双(2,4,6-三异丙基苯基)苯基]-苯基-环己基膦。
。
由镁屑(0.67 g, 27.5 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(7.08 g,25.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF (15.0 mL), 冷却到-78℃, 滴加5.0 mL正丁基锂(2.4 M正己烷溶液,12.0 mmol),搅拌反应1 h后, 通过双针尖加入上述待用的格式试剂, 升至室温再于油浴80℃下回流6 h. 冷却至室温再将反应液转移到另一个带有溴化亚铜(2.15 g, 15.0mmol)的250 mL两口瓶中, 搅拌反应15 min后冷却到-78℃, 加入二氯苯基膦(2.68 g,15.0 mmol)的THF (5.0 mL)溶液, 升至室温反应12 h后再于油浴70℃下回流6 h. 冷却至-78℃, 再通过注射器加入15.0 mL环己基溴化镁(1.0 M in THF, 15.0 mmol)溶液, 室温反应12 h后再回流12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(30mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体4.91 g, 产率73 %。
MP: 146.5-148.1℃。
1H NMR (400 MHz, CDCl3) δ: 7.36 – 7.30 (m, 1H), 7.15 (dd, J = 7.6, 1.8Hz, 3H), 7.06 – 6.96 (m, 6H), 6.88 (s, 2H), 2.97 (s, 4H), 2.69 – 2.60 (m,2H), 1.34 (d, J = 6.9 Hz, 17H), 1.29 – 1.20 (m, 1H), 1.02 (ddd, J = 16.8,13.2, 6.7 Hz, 27H), 0.89 – 0.78 (m, 2H)。
13C NMR (101 MHz, CDCl3) δ: 147.80, 146.67, 146.52, 146.20, 146.05,146.05, 138.10, 138.05, 135.25, 135.03, 132.04, 132.02, 127.75, 127.13,127.05, 126.53, 120.84, 120.45, 34.23, 33.01, 32.68, 32.04, 31.91, 31.02,30.95, 30.93, 30.68, 30.61, 26.86, 26.81, 26.74, 26.68, 25.98, 25.85, 24.21,24.15, 22.58, 22.44。
31P NMR (162 MHz, CDCl3) δ: 6.72。
HR-MS m/z (%): Calcd for C48H66P [M+ + H] 673.4897; Found 673.4944(100)。
实施例14. [2,6-双(2,4,6-三异丙基苯基)苯基]-甲基-叔丁基膦(ZTPhos)。
。
由镁屑(0.56 g,23.0 mmol)、THF (10 mL)与2,4,6-三异丙基溴苯(6.23 g, 22.0mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却至-78℃, 滴加4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应1 h后, 仍在此温度下通过双针尖加入上述待用的格式试剂, 升至室温再于油浴80℃下回流6 h. 冷却至室温转移到另一个带有溴化亚铜(1.72 g, 12.0 mmol)干燥的250 mL 两口瓶中,搅拌反应15 min再冷却到-78℃, 通过双针尖加入二氯叔丁基膦(1.90 g, 12.0 mmol)和THF (5 mL)的溶液, 升至室温反应12 h后再于油浴70℃下回流6h. 冷却至-78℃, 通过注射器加入12.0 mL甲基溴化镁溶液(1.0 M in THF, 12.0 mmol),升至室温反应12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(30 mL).合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 =50:1), 得白色固体3.09 g, 产率53 %。
MP: 145.3-146.7℃。
1H NMR (400 MHz, CDCl3) δ: 7.33 – 7.27 (m, 1H), 7.16 (d, J = 7.5 Hz,2H), 7.05 (d, J = 5.9 Hz, 4H), 2.98 (dp, J = 13.5, 6.5 Hz, 2H), 2.80 (ddq, J= 26.6, 13.1, 6.6 Hz, 4H), 1.45 – 1.25 (m, 24H), 1.04 (dd, J = 10.1, 6.8 Hz,12H), 0.96 (d, J = 7.0 Hz, 3H), 0.76 (t, J = 14.2 Hz, 9H)。
13C NMR (101 MHz, CDCl3) δ: 148.15, 147.96, 147.82, 146.22, 145.92,139.18, 139.13, 137.37, 136.95, 131.90, 131.87, 126.54, 120.64, 120.09,34.19, 31.02, 30.97, 30.95, 29.87, 29.68, 29.51, 29.35, 26.15, 25.83, 24.29,24.05, 22.62, 8.33, 8.11。
31P NMR (162 MHz, CDCl3)δ: -3.33。
HR-MS m/z (%): Calcd for C41H62P [M+ + H] 585.4853; Found 585.4857(100)。
实施例15. [2,6-双(2,4,6-三异丙基苯基)苯基]-苯基-异丙基膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(6.23 g,22.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF (15 mL), 冷却至-78℃, 滴加4.8 mL正丁基锂(2.5 M正己烷溶液,12.0 mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 冷却至室温将反应液转移到装有溴化亚铜(1.72 g, 12.0 mmol)的250 mL 两口瓶中, 搅拌反应15 min后冷却到-78℃, 加入二氯苯基膦(2.15 g, 12.0 mmol)和THF (5.0 mL)的混合液, 升至室温反应12 h, 再于油浴70℃下回流6 h. 冷却至-78℃, 通过注射器加入4.0 mL异丙基溴化镁溶液(3.0 M in THF,12.0 mmol), 升至室温后再反应12 h.加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体3.98 g, 产率63%。
MP: 144.3-146.2℃。
1H NMR (400 MHz, CDCl3) δ: 7.40 – 7.34 (m, 1H), 7.21 (d, J = 7.0 Hz,4H), 7.16 – 7.07 (m, 2H), 6.99 (t, J = 9.5 Hz, 4H), 6.66 (s, 1H), 3.28 – 3.17(m, 1H), 3.06 (s, 2H), 2.89 (s, 2H), 2.72 – 2.62 (m, 1H), 2.55 (s, 1H), 1.47– 1.39 (m, 15H), 1.35 (d, J = 6.9 Hz, 6H), 1.32 (d, J = 6.8 Hz, 3H), 1.06 (d,J = 6.6 Hz, 4H), 1.00 – 0.90 (m, 5H), 0.77 (d, J = 6.7 Hz, 5H), 0.66 (dd, J =15.5, 6.7 Hz, 3H)。
31P NMR (162 MHz, CDCl3) δ: -4.19。
HR-MS m/z (%): Calcd for C45H62P [M+ + H] 633.4583; Found 633.4580(100)。
实施例16. [2,6-双(2,4,6-三异丙基苯基)苯基]-二环己基膦(XTPhos)。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(6.23 g,22.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF (15 mL), 冷却至-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液,12.0 mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温, 再于油浴70℃下回流12 h. 冷至室温后将反应液转移到一个装有溴化亚铜(1.72g, 12.0 mmol)的250 mL 两口瓶中, 搅拌反应15 min后冷却到-78℃, 加入二环己基氯膦(2.79 g, 12.0 mmol)和THF (5.0 mL)的混合液, 升至室温反应12 h, 再于油浴70℃下回流6 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得白色固体4.13 g,产率61%。
MP: 147.5-149.1℃。
1H NMR (400 MHz, CDCl3) δ: 7.30 – 7.25 (m, 1H), 7.14 – 7.12 (m, 1H),7.11 – 7.10 (m, 1H), 7.07 (s, 4H), 3.01 – 2.92 (m, 2H), 2.84 – 2.72 (m, 4H),1.83 – 1.71 (m, 3H), 1.63 – 1.53 (m, 5H), 1.48 – 1.40 (m, 5H), 1.36 (dd, J =11.7, 6.9 Hz, 24H), 1.22 – 1.15 (m, 2H), 1.11 – 1.04 (m, 2H), 1.00 (d, J =6.7 Hz, 13H), 0.89 – 0.81 (m, 4H)。
13C NMR (101 MHz, CDCl3)δ: 147.55, 147.38, 145.70, 139.30, 139.25,131.82, 131.79, 126.53, 120.79, 34.16, 34.06, 33.79, 31.92, 31.75, 30.74,30.62, 30.50, 27.35, 27.27, 27.17, 27.01, 26.38, 25.98, 24.16, 23.12。
31P NMR (162 MHz, CDCl3) δ: 9.62, 9.52。
HR-MS m/z (%): Calcd for C48H72P [M+ + H] 679.5366; Found 679.5367(100)。
实施例 17. [2,6-双(2,4,6-三异丙基苯基)苯基]-(2’,6’-二甲氧基-2-联苯基)-甲基膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(6.23 g,22.0 mmol)制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却至-78℃, 滴加4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 冷却到-78℃, 通过注射器加入三氯化膦(1.65 g,12.0 mmol), 加毕升至室温反应6 h, 待用。
由镁屑(0.39 g, 16.0 mmol)、THF (15.0 mL)与2,6-二甲氧基-2’-溴联苯(4.39g, 15.0 mmol)制成格氏试剂. 在室温下将反应液转移到另一个250 mL带有氯化亚铜(1.49 g, 15.0mmol)两口瓶中, 搅拌反应15 min后冷却到-78℃, 在此温度下通过双针尖将上述250 mL两口瓶中的反应液转移至该瓶中, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 冷却至-78℃, 通过注射器加入15.0 mL甲基溴化镁溶液(1.0 M in THF, 15.0mmol), 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 加入60 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(80 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.89 g, 产率39 %。
31P NMR (162 MHz, CDCl3)δ: 7.12。
实施例18. [2,6-双(2-甲氧基-1-萘基)苯基]-二苯基膦。
。
由镁屑(0.67 g, 27.5 mmol)、THF (10 mL)与1-溴-2-甲氧基萘(5.93 g, 25.0mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 加入5.0 mL正丁基锂(2.4 M正己烷溶液, 12.0mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴70℃下回流12 h. 冷却至室温后将反应液转移到一个装有四三苯基膦钯(0.17g, 0.15 mmol)的100 mL 两口瓶中, 搅拌反应20 min后冷却到-78℃, 通过注射器加入二苯基氯膦(3.31 g, 15.0 mmol), 升至室温再于油浴70℃下回流6 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体3.05 g, 产率53%。
MP: 153.2-155.0℃。
1H NMR (400 MHz, CDCl3)δ: 7.72 – 7.57 (m, 5H), 7.42 (dd, J = 7.5, 5.7Hz, 4H), 7.30 (ddd, J = 7.4, 4.5, 2.5 Hz, 4H), 7.06 – 6.98 (m, 2H), 6.90 –6.77 (m, 6H), 6.72 (t, J = 7.4 Hz, 4H), 3.55 (d, J = 4.4 Hz, 6H)。
13C NMR (101 MHz, CDCl3) δ: 154.07, 143.67, 143.51, 136.63, 136.39,136.20, 136.07, 134.03, 133.71, 133.50, 132.14, 132.12, 129.27, 128.51,127.73, 126.76, 126.44, 126.36, 126.06, 125.46, 124.77, 124.72, 122.98,112.16, 55.26。
31P NMR (162 MHz, CDCl3)δ: -4.54。
HR-MS m/z (%): Calcd for C40H32O2P [M+ + H] 575.2134; Found 575.2151(100)。
实施例19. [2,6-双(2-甲氧基-1-萘基)苯基]-二环己基膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10 mL)与1-溴-2-甲氧基萘(5.22 g, 22.0mmol) 制成格氏试剂. 另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0 mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0 mmol)搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴70℃下回流12 h. 冷至室温后将反应液转移到一个装有溴化亚铜(1.72 g,12.0 mmol)的100mL两口瓶中, 搅拌20 min后冷却到-78℃, 加入二环己基氯膦(2.79 g, 12.0 mmol)和THF(5 mL)的混合液, 升至室温再于油浴40℃下回流12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.58 g, 产率44 %。
MP: 156.3-157.6℃。
1H NMR (400 MHz, CDCl3) δ: 7.94 (d, J = 9.0 Hz, 2H), 7.86 (d, J = 7.8Hz, 2H), 7.43 – 7.33 (m, 8H), 7.27 (d, J = 8.0 Hz, 3H), 3.98 – 3.90 (m, 6H),1.48 – 1.19 (m, 11H), 0.95 – 0.41 (m, 11H)。
13C NMR (101 MHz, CDCl3)δ:153.59, 144.78, 144.62, 139.65, 139.34,134.59, 131.61, 131.57, 128.87, 128.69, 128.40, 127.80, 127.15, 127.10,126.06, 125.81, 123.19, 112.86, 57.01, 56.03, 33.11, 32.95, 32.93, 32.71,31.55, 31.38, 29.74, 27.07, 27.01, 26.94, 26.91, 26.35。
31P NMR (162 MHz, CDCl3)δ: 9.76。
HR-MS m/z (%): Calcd for C40H43P [M] 586.2995; Found 586.2965 (100)。
实施例20. [2,6-双(2-甲氧基-1-萘基)苯基]-(4-二甲氨基苯基)-环己基膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10 mL)与1-溴-2-甲氧基萘(5.22 g, 22.0mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol),搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴70℃下回流12 h. 冷至室温后将反应液转移到一个装有氯化亚铜(1.20 g, 12.0mmol)的250 mL两口瓶中,搅拌20 min后冷却到-78℃, 加入二氯环己基膦(2.22 g, 12.0mmol)和THF (5 mL)的混合液, 升至室温再于油浴40℃下回流6 h. 冷却至-50℃, 加入4-N,N-二甲基氨基苯基溴化镁溶液(24.0 mmol), 油浴70℃反应3天. 加入40 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.84 g, 产率45%。
MP: 157.2-158.9℃。
1H NMR (400 MHz, CDCl3) δ: 7.93 (dd, J = 8.9, 6.3 Hz, 3H), 7.77 – 7.69(m, 1H), 7.57 – 7.51 (m, 3H), 7.44 (d, J = 9.1 Hz, 2H), 7.29 – 7.24 (m, 2H),7.20 – 7.13 (m, 2H), 7.10 – 7.05 (m, 1H), 7.02 – 6.98 (m, 1H), 6.28 (s, 2H),5.98 (d, J = 8.0 Hz, 2H), 4.01 (s, 3H), 3.76 (s, 3H), 2.80 (s, 6H), 2.11 –2.00 (m, 1H), 1.82 – 1.54 (m, 4H), 1.48 – 1.17 (m, 4H), 1.11 – 0.86 (m, 3H)。
13C NMR (101 MHz, CDCl3) δ: 153.76, 153.74, 153.59, 149.15, 145.11,144.86, 144.02, 143.93, 138.73, 138.42, 134.59, 134.42, 134.40, 134.28,134.07, 132.03, 132.01, 131.36, 131.31, 129.10, 128.82, 128.72, 128.71,128.47, 127.95, 126.99, 126.22, 126.16, 125.98, 125.50, 123.07, 122.81,120.29, 120.18, 112.57, 112.49, 111.56, 111.49, 56.27, 55.34, 50.80, 40.37,32.13, 32.06, 30.36, 30.19, 30.14, 26.94, 26.84, 26.71, 26.60。
31P NMR (162 MHz, CDCl3) δ: -9.15。
HR-MS m/z (%): Calcd for C42H42NO2P [M] 623.2947; Found 623.2930 (100)。
实施例21. [2,6-双(2-甲氧基-1-萘基)苯基]-双[3,5-二(三氟甲基)苯基]膦。
。
由镁屑(0.29 g, 12.0 mmol)、THF (5 mL)与1-溴-2-甲氧基萘(2.61 g, 11.0mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(0.74 g, 5.0mmol)和THF (10 mL), 冷却到-78℃, 加入2.4 mL正丁基锂(2.5 M正己烷溶液, 6.0mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温,再于油浴70℃下回流12 h. 冷至室温后将反应液转移到一个装有氯化亚铜(0.6 g, 6.0mmol)的250 mL两口瓶中, 搅拌20 min后冷却到-78℃, 加入双[3,5-二(三氟甲基)苯基]氯化膦, 升至室温再于油浴加热下回流6 h. 加入50 mL氨水(26.0%-28.0%)并搅拌30min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩,残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体2.03 g, 产率48%。
MP: 151.1-152.6℃。
1H NMR (400 MHz, CDCl3) δ: 7.77 – 7.69 (m, 5H), 7.55 – 7.49 (m, 2H),7.45 – 7.42 (m, 4H), 7.41 (d, J = 2.7 Hz, 1H), 7.40 – 7.38 (m, 1H), 7.38 –7.36 (m, 1H), 7.35 (d, J = 1.2 Hz, 1H), 7.33 (d, J = 6.9 Hz, 4H), 7.08 (d, J= 9.1 Hz, 2H), 3.68 (s, 6H)。
13C NMR (101 MHz, CDCl3) δ: 154.29, 143.38, 143.22, 138.54, 138.35,133.63, 133.01, 132.78, 132.57, 132.54, 130.76, 130.25, 128.36, 128.02,127.00, 124.57, 123.78, 121.82, 121.75, 112.56, 55.60, 1.11。
31P NMR (162 MHz, CDCl3) δ: -3.12。
HR-MS m/z (%): Calcd for C44H27F12O2P [M] 846.1552; Found 846.1552(100)。
实施例22. [2,6-双(2-甲氧基-6-二甲氨基苯基)苯基]-二苯基膦。
。
由镁屑(0.56 g, 23.0mmol)、THF (10.0 mL)与2-甲氧基(6-二甲基氨基)碘苯(6.10 g, 22.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g, 10.0 mmol)和THF (15 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0 mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温再于油浴70℃下回流12 h. 至室温备后将反应液转移到一个装有氯化亚铜(1.20 g, 12.0 mmol)干燥的250 mL两口瓶中, 搅拌反应15 min后冷却到-78℃, 通过注射器加入二苯基氯膦(2.65 g, 12.0 mmol), 升至室温反应6 h. 加入50 mL氨水(26.0%-28.0%)并搅拌30 min, 用二氯甲烷萃取三次(50 mL), 有机相再用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(30 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体1.57 g, 产率28 %。
1H NMR (400 MHz, CDCl3)δ: 7.73 – 7.62 (m, 3H), 7.35 – 7.27 (m, 7H),7.19 – 7.12 (m, 3H), 6.41 – 6.28 (m, 6H), 3.80 (s, 6H), 2.94 (s, 12H)。
31P NMR (162 MHz, CDCl3) δ: -13.62, -13.66。
实施例23. [2,6-双(2,4,6-三异丙基苯基)苯基]-二(2-噻吩基)膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(6.23 g,22.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF (15 mL), 冷却至-78℃, 滴加4.8 mL正丁基锂(2.5 M正己烷溶液,12.0 mmol), 搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 冷却到-78℃, 通过注射器加入三氯化膦(1.65 g, 12.0 mmol), 加毕升至室温反应6 h, 待用.
由镁屑(0.90 g, 37.0 mmol)、THF (15.0 mL)与2-溴噻吩(5.87 g, 36.0 mmol) 制成格氏试剂. 冷却到室温将反应液转移到另一个250 mL带有氯化亚铜(1.19 g, 12.0mmol)两口瓶中, 搅拌反应15 min后冷却到-78℃, 在此温度下通过双针尖将上述250 mL两口瓶中的反应液转移至该瓶中, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌50 min, 用二氯甲烷萃取三次(150 mL), 合并的有机相用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(50 mL), 有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚), 得蓝色固体3.59 g, 产率53%。
MP: 144.3-145.5℃。
1H NMR (400 MHz, CDCl3) δ: 7.47 – 7.40 (m, 1H), 7.26 – 7.23 (m, 2H),7.23 – 7.18 (m, 2H), 6.88 (s, 4H), 6.79 – 6.75 (m, 2H), 6.75 – 6.70 (m, 2H),2.85 (s, 6H), 1.30 (d, J = 6.9 Hz, 12H), 1.04 – 0.92 (m, 24H)。
13C NMR (101 MHz, CDCl3) δ: 147.80, 146.63, 146.45, 146.19, 146.18,139.55, 139.29, 136.76, 136.70, 135.63, 135.40, 135.20, 134.96, 132.31,132.28, 131.55, 131.52, 127.93, 126.69, 126.63, 120.64, 34.17, 31.13, 25.58,24.09, 22.70。
31P NMR (162 MHz, CDCl3) δ: -33.31。
HR-MS m/z (%): Calcd for C44H56S2P [M++H] 679.3555; Found 679.3560(100)。
实施例24. [2,6-双(2,6-二甲氧基苯基)苯基]-二环己基膦(STPhos)。
。
由镁屑(0.67 g, 27.5 mmol)、THF (10.0 mL)与2,6-二甲氧基溴苯(5.40 g,25.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF (15.0 mL), 冷却到-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液,12.0 mmol), 搅拌反应2 h后, 在次温度下将上述制备格式试剂通过双针尖转移至两口瓶中, 撤去冷浴自然升至室温, 再于油浴70℃下回流12 h.冷却到-78℃, 加入二氯环己基膦(2.68 g, 15.0 mmol)的THF (5.0 mL)溶液, 撤去冷浴自然升至室温, 再于油浴70℃下回流6 h. 冷却至-78℃, 再通过双针尖将15.0 mL环己基溴化镁(1.0 M in THF, 15.0mmol)和氯化亚铜(1.49 g, 15.0 mmol)的THF (10.0 mL)溶液转移至两口瓶中, 撤去冷浴自然升至室温,再于油浴70℃下回流12 h. 加入40 mL氨水(26.0%-28.0%)并搅拌50 min,用二氯甲烷萃取三次(100 mL), 有机相用50 mL饱和氯化钠溶液洗涤, 水相再用二氯甲烷萃取三次(50 mL). 合并的有机相用Na2SO4干燥后减压浓缩, 残余物硅胶柱层析分离提纯(石油醚:乙酸乙酯 = 10:1), 得白色固体0.87 g, 产率16%。
1H NMR (400 MHz, CDCl3) δ: 7.48 – 7.43 (m, 1H), 7.39 – 7.34 (m, 1H),7.34 – 7.29 (m, 1H), 7.19 – 7.14 (m, 2H), 6.70 – 6.68 (m, 2H), 6.68 – 6.65(m, 2H), 3.80 – 3.74 (m, 12H), 1.81 – 1.52 (m, 9H), 1.47 – 1.13 (m, 10H),1.01 – 0.82 (m, 3H)。
31P NMR (162 MHz, CDCl3) δ: 4.54。
实施例25. [2,6-双(2,4,6-三异丙基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦。
。
由镁屑(0.56 g, 23.0 mmol)、THF (10.0 mL)与2,4,6-三异丙基溴苯(6.23 g,22.0 mmol) 制成格氏试剂. 往另一个干燥的250 mL两口瓶中加入间二氯苯(1.47 g,10.0 mmol)和THF(15 mL), 冷却至-78℃, 加入4.8 mL正丁基锂(2.5 M正己烷溶液, 12.0mmol),搅拌反应2 h后, 仍在此温度下通过双针尖加入上述制备的格式试剂, 升至室温,再于油浴70℃下回流12 h. 冷却到-78℃, 通过注射器加入三氯化膦(1.65 g, 12.0mmol), 加毕升至室温反应6 h, 待用.
由镁屑(0.39 g, 16.0 mmol)、THF (10.0 mL)与3,5-二(三氟甲基)溴苯(4.40 g,15.0 mmol) 制成格氏试剂. 冷却到室温将反应液转移到另一个250 mL带有氯化亚铜(1.48 g, 15.0 mmol)两口瓶中, 搅拌反应30 min后冷却到-78℃, 在此温度下通过双针尖将上述250 mL两口瓶中的反应液转移至该瓶中, 撤去冷浴升至室温, 再于油浴70℃下回流12 h. 冷到室温后, 加入40 mL氨水(26.0%-28.0%)并搅拌50 min, 用二氯甲烷萃取三次(150 mL), 合并的有机相用50 mL饱和氯化钠溶液洗涤, 水层再用二氯甲烷萃取三次(50 mL), 有机相用Na2SO4干燥后减压浓缩, 残余物经硅胶柱层析分离提纯(石油醚), 得白色固体4.03 g, 产率43%。
MP: 139.7-141.2℃。
1H NMR (400 MHz, CDCl3) δ: 8.03 (s, 2H), 7.80 (d, J = 7.0 Hz, 4H),7.48 – 7.37 (m, 1H), 7.22 (d, J = 7.4 Hz, 2H), 7.10 (d, J = 8.5 Hz, 4H), 3.05– 2.92 (m, 2H), 2.82 – 2.72 (m, 1H), 2.67 – 2.55 (m, 3H), 1.40 – 1.34 (m,12H), 1.20 (t, J = 6.0 Hz, 11H), 1.16 (t, J = 6.1 Hz, 11H), 1.10 (s, 1H),1.08 (s, 1H)。
13C NMR (101 MHz, CDCl3) δ: 148.30, 146.47, 145.92, 142.38, 137.48,137.31, 136.54, 133.37, 133.34, 133.19, 133.12, 129.78, 128.49, 127.84,126.50, 124.46, 124.42, 124.38, 124.08, 121.36, 120.69, 120.43, 34.28, 34.19,30.89, 30.40, 29.73, 24.65, 24.30, 24.11, 24.08, 24.05, 23.51。
31P NMR (162 MHz, CDCl3) δ: -4.15。
实施例26. 反式-双[2,6-双(2-甲氧基苯基)苯基-二苯基膦]二氯化钯(II)。
。
惰气气氛下,往一个干燥的50 mL 史莱克瓶中, 加入[2,6-双(2-甲氧基苯基)苯基]-二苯基膦(240.0 mg, 0.5 mmol)与双乙腈二氯化钯(65.0 mg, 0.25 mmol), 通过注射器加入5 mL二氯甲烷, 搅拌反应6 h. 减压浓缩除去溶剂, 残余物硅胶柱层析分离提纯(二氯甲烷), 得黄色固体0.23 g, 产率77%。
1H NMR (500 MHz, DMSO) δ: 7.50 – 7.44 (m, 1H), 7.25 – 7.17 (m, 3H),7.15 – 7.13 (m, 1H), 7.11 – 6.96 (m, 12H), 6.91 – 6.85 (m, 2H), 6.74 – 6.63(m, 2H), 6.52 – 6.46 (m, 2H), 3.59 (s, 3H), 3.38 (s, 3H)。
31P NMR (162 MHz, DMSO) δ: 30.94。
实施例27. 双[(4-甲基-2,6-二苯基-苯基)-二苯基膦]钯。
。
惰气气氛下, 往一个干燥的50 mL史莱克瓶中,加入(2,6-二苯基-4-甲基苯基)-二苯基膦(236 mg, 0.55 mmol)与Me2Pd(Ⅱ)(TMEDA) (67 mg, 0.25 mmol), 通过注射器加入2 mL二氯甲烷, 搅拌反应6 h.抽去溶剂, 残余物用丙酮重结晶,得黑色固体0.21 g,产率70%。
31P NMR (162 MHz, CDCl3) δ: 26.04。
实施例28. (N,N-二甲基苯甲胺-2-基-ƞ2-C,N)-[(2,6-二苯基-4-甲基-苯基)-二苯基膦]氯化钯(Ⅱ)。
。
惰气气氛下, 往一个干燥的50 mL 史莱克瓶中, 加入(2,6-二苯基-4-甲基苯基)-二苯基膦(214.0 mg, 0.5 mmol)与二聚苄胺钯(138.0 mg, 0.25 mmol), 通过注射器加入5 mL二氯甲烷, 搅拌反应6 h. 减压浓缩除去溶剂, 残余物硅胶柱层析分离提纯(二氯甲烷), 得黄色固体0.31 g, 产率90%。
1H NMR (400 MHz, CDCl3) δ: 7.50 – 7.33 (m, 5H), 7.12 – 7.02 (m, 3H),7.02 – 6.94 (m, 3H), 6.94 – 6.90 (m, 3H), 6.89 (s, 2H), 6.88 – 6.86 (m, 1H),6.85 (d, J = 3.1 Hz, 3H), 6.74 – 6.67 (m, 2H), 6.17 – 6.10 (m, 1H), 5.55 –5.49 (m, 1H), 3.99 (d, J = 1.2 Hz, 2H), 2.91 (d, J = 2.4 Hz, 6H), 2.30 (s,3H)。
13C NMR (101 MHz, CDCl3) δ: 149.05, 148.20, 148.18, 146.75, 146.67,142.78, 142.74, 138.48, 138.46, 137.52, 137.42, 137.14, 137.03, 132.81,132.73, 131.34, 130.86, 129.44, 129.41, 127.25, 127.14, 126.19, 124.38,124.32, 123.56, 122.08, 50.63, 50.61, 29.72, 20.89。
31P NMR (162 MHz, CDCl3) δ: 42.51。
HR-MS m/z (%): Calcd for C40H37NPPd [M+-Cl] 668.1708; Found 668.1755(100)。
实施例29. (2’-氨基苯乙烷-2-ƞ2-C,N)-[(2,6-二苯基-4-甲基苯基)-二苯基膦]氯化钯(Ⅱ)。
。
惰气气氛下, 往一个干燥的50 mL 史莱克瓶中, 加入(2,6-二苯基-4-甲基苯基)-二苯基膦(214.0 mg, 0.5 mmol)与二聚苯乙胺钯(130.0 mg, 0.25 mmol), 通过注射器加入10 mL二氯甲烷, 搅拌反应6 h. 减压浓缩除去溶剂, 残余物硅胶柱层析分离提纯(二氯甲烷), 得黄色固体0.27 g, 产率80%。
1H NMR (400 MHz, CDCl3) δ: 8.06 – 7.95 (m, 1H), 7.76 – 7.69 (m, 1H),7.64 – 7.30 (m, 12H), 7.21 – 7.10 (m, 4H), 7.08 – 6.91 (m, 4H), 6.65 – 6.58(m, 2H), 6.56 – 6.50 (m, 1H), 6.49 – 6.42 (m, 2H), 2.46 – 2.40 (m, 3H), 1.58– 1.52 (m, 4H), 1.47 – 1.44 (m, 2H)。
31P NMR (162 MHz, CDCl3) δ: 22.69。
实施例30. (2’-甲氨基联苯-2-基-ƞ2-C,N)-[(2,6-双(2,4,6-三异丙基苯基)苯基)-二环己基膦]甲基磺酸钯(Ⅱ)。
。
惰气气氛下, 往一个干燥的50 mL史莱克瓶中,加入[2,6-双(2,4,6-三异丙基苯基)苯基]-二环己基膦(271.0 mg, 0.4 mmol)与[(2’-甲氨基联苯-2-基-C,N)氯化钯]2(148.0 mg, 0.2 mmol), 及5 mL二氯甲烷, 搅拌反应6 h. 减压浓缩除去溶剂, 残余物硅胶柱层析分离提纯(二氯甲烷洗脱), 得黄色固体0.37 g, 产率89%。
31P NMR (162 MHz, CDCl3) δ: 59.07, 25.02。
实施例31. [(2,6-双(2,4,6-三异丙基苯基)苯基)-二环己基膦]-烯丙基-氯化钯(Ⅱ) [(XTPhos)(all)PdCl]。
。
惰气气氛下, 往一个干燥的50 mL 史莱克瓶中, 加入[2,6-双(2,4,6-三异丙基苯基)苯基]-二环己基膦(135.0 mg, 0.2 mmol)与烯丙基氯化钯(Ⅱ)二聚体 (36.0 mg,0.1 mmol), 及3 mL二氯甲烷, 搅拌反应6 h. 减压浓缩除去溶剂, 残余物硅胶柱层析分离提纯(二氯甲烷), 得黄色固体0.15 g, 产率90%。
31P NMR (162 MHz, CDCl3) δ: 67.00。
实施例32-38.
[a]在手套箱中,将1.1 mmol卤代芳烃、1.0 mmol二苯胺、1.2 mmol叔丁醇钠、适量的配体和钯(Ⅱ)、0.13 mL十二烷(GC内标)和 2 mL无水甲苯置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相.
[b]氮气气氛下, 往一个干燥的100 mL 三口瓶, 加入搅拌子并装上冷凝管和恒压漏斗, 加入二苯胺(0.846 g, 5.0 mmol)、4-氯苯甲醚(0.784 g, 5.5 mmol)和二甲苯(9.0mL), 冰浴冷却至5℃, 通过注射器滴加甲基氯化镁(1.7 mL, 3.0 mol/L, 5.1 mmol), 约需 10 min, 再加入配体、钯(II)和0.26 mL十二烷(GC分析的内标)的二甲苯(1.0 mL)溶液. 在145℃的油浴中反应. GC分析有机相。
实施例39-40.
[a] 在手套箱中,将1.1 mmol卤代芳烃、1.0 mmol二苯胺、1.2 mmol叔丁醇钠、适量的配体和钯(Ⅱ)、0.13 mL十二烷(GC分析的内标)和 2 mL无水甲苯置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相。
实施例41.
[a] 在手套箱中, 将1.0 mmol卤代芳烃、1.5 mmol苯硼酸、3.0 mmol氟化铯、适量的配体和钯(Ⅱ) (P:Pd = 1:1)、0.13 mL十二烷(作为GC分析的内标)和 2 mL无水二氧六环置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相.
[b] R. C. Smith, et al., Tetrahedron Letters 2004, 45, 8327-8330.
[c]
。
实施例42-43.
[a]在手套箱中,将1.1 mmol卤代芳烃、1.0 mmol咔唑、1.2 mmol叔丁醇钠、适量的配体和钯(Ⅱ)、0.13 mL十二烷(GC分析的内标)和 2 mL无水甲苯置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相.
[b] Ken Suzuki, et al., Adv. Synth. Catal. 2008, 350, 652-656.
[c]
。
实施例44.
[a]在手套箱中,将1.0 mmol卤代芳烃、1.5 mmol***啉、1.2 mmol叔丁醇钠、适量的配体和钯(Ⅱ)、0.13 mL十二烷(作为GC分析的内标)和 2 mL无水甲苯置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相.
[b] Azusa Kondon, et al., J. Am. Chem. Soc. 2007, 129, 6996-6997.
[c]
。
实施例45.
[a]在手套箱中,将1.0 mmol卤代芳烃、1.5 mmol苯硼酸、3.0 mmol磷酸钾、适量的配体和钯(Ⅱ)、0.13 mL十二烷(作为GC分析的内标)和 2 mL无水甲苯置于耐压管中. 将该管密封并悬浮在100℃的油浴中. GC分析有机相.
[b] Stephen L. Buchwald, et al., Angew. Chem. Int. Ed. 2004, 43, 1871-1876.
[c]
Claims (11)
1.通式为Ia和Ib或它们的混合物的三联芳单膦配体:
其中
Ar 选自(C6-C20)芳基, 其可以有1到3个独立地选自(C1-C6)烷基、-O(C1-C6)烷氧基、-N(C1-C6)2二烷基氨基或(C6-C10)芳基(这里的芳基同样可以有1到3个独立地选自(C1-C6)烷基、-O(C1-C6)烷氧基或-N(C1-C6)2二烷氨基的取代基)的取代基;
R1选自H、(C1-C6)烷基、-O(C1-C6)烷氧基或-N(C1-C6)2二烷基氨基;
R2和R3各自独立地选自(C1-C10)烷基、(C3-C10)环烷基、(5-11元)杂环烷基、(C6-C20)芳基、(C4-C20)杂芳基或-CH2(C6-C10)芳亚甲基, 这里的(C3-C10)环烷基、(5-11元)杂环烷基、(C6-C20)芳基、(C4-C20)杂芳基和-CH2(C6-C10)芳亚甲基中可以有1到3个独立地选自(C1-C6)烷基、-O(C1-C6)烷氧基或-N(C1-C6)2二烷氨基的取代基, 这里的杂环烷基和杂芳基中的杂原子各自独立地选自O、N或S原子;
当R1 = H且Ar = 苯基时, R2 或和R3不同时为叔丁基;
当R1 = H且当R2 = R3 = 甲基时, Ar不为2,6-二甲基苯基、2,6-二异丙基苯基、2,4,6-三甲基苯基或2,4,6-三异丙基苯基;
当R1 = H且当R2 = R3 = 乙基时, Ar不为2,6-二甲基苯基、2,4,6-三甲基苯基或2,6-二异丙基苯基。
2.根据权利要求1, Ar可以进一步选自苯基、4-甲基苯基、4-甲氧基苯基、4-异丙基苯基、4-叔丁基苯基、4-(二甲氨基)苯基、4-氟苯基、3,5-二甲基苯基、3,5-二叔丁基苯基、2-甲基苯基、2-甲氧基苯基、2-(二甲氨基)苯基、2-异丙基苯基、2,6-二甲基苯基、2,6-二异丙基苯基、2,6-二甲氧基苯基、2,6-二异丙氧基苯基、2,6-双(二甲氨基)苯基、2,6-二甲氧基-3,5-二苯基-苯基、2,6-二甲氧基-3,5-双(3,5-二甲基苯基)-苯基、2,6-二异丙氧基-3,5-二苯基-苯基、2,6-二甲氧基-3,5-双(2,4,6-三异丙基苯基)-苯基、2-甲氧基-6-(二甲氨基)苯基、2,4,6-三甲基苯基、2,4,6-三甲氧基苯基、2,4,6-三异丙基苯基、二茂铁基、1-萘基、2-萘基、2-甲氧基-1-萘基或9-蒽基的一种。
3.根据上述权利要求, R1可以进一步选自H、甲基、甲氧基、二甲氨基、异丙基或叔丁基中的一种。
4.根据上述权利要求, R2和R3可以进一步各自独立地精选自甲基、乙基、丙基、异丙基、正丁基、叔丁基、环戊基、环己基、金刚基、苯基、2-甲基苯基、2-异丙基苯基、2-甲氧基苯基、2-(二甲氨基)苯基、4-甲基苯基、4-氟苯基、4-甲氧基苯基、4-(二甲氨基)苯基、3,5-二甲基苯基、3,5-双(三氟甲基)苯基、3,5-二氟苯基、3,5-二叔丁基苯基、2,6-二甲基苯基、2,6-二甲氧基苯基、2,6-二异丙基苯基、2,4,6-三甲氧基苯基、2-联苯基、2’,6’-二甲基-2-联苯基、2’,6’-二甲氧基-2-联苯基、2’,6’-二异丙氧基-2-联苯基、2’,6’-双二甲氨基基-2-联苯基、2’,6’-二异丙基-2-联苯基、2’,4’,6’-三异丙基-2-联苯基、二茂铁基、2-呋喃基、2-噻吩基、2-苯并呋喃基、2-苯并噻吩基、2-吡啶基或2-四氢呋喃基。
5.根据上述权利要求, 本发明提供的三联芳单膦配体所选自的取代基可以构成下面具体膦化合物:
(2,6-二苯基-4-甲基苯基)-二苯基膦;
(2,6-二苯基-4-甲基苯基)-二环己基膦;
(2,6-二苯基-4-甲基苯基)-二叔丁基膦;
[2,6-双(2-甲基苯基)苯基]-二苯基膦;
[2,6-双(2-甲基苯基)苯基]-二环己基膦;
[2,6-双(2-甲基苯基)苯基]-二叔丁基膦;
[2,6-双(2,6-二甲基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2,6-二甲基苯基)苯基]-叔丁基-2-呋喃基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-苯基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-环己基膦;
[2,6-双(2,4,6-三甲基苯基)苯基]-[2-二甲氨基苯基]-叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-二苯基膦;
[2,6-双(2-甲氧基苯基)苯基]-二环己基膦;
[2,6-双(2-甲氧基苯基)苯基]-二叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2-甲氧基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2-甲氧基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-苯基-异丙基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-环己基-2-噻吩基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-环己基-金刚基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二甲氧基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二异丙氧基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二异丙氧基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-异丙基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲基-2-联苯基]-甲基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-甲基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-[2’,6’-二异丙基-2-联苯基]-环己基膦;
[2,6-双(2,6-二异丙基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,6-二异丙基苯基)苯基]-苯基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-二环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-苯基-环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-甲基-叔丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-环己基-异丙基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲基-2-联苯基]- 正丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-甲基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二甲氧基-2-联苯基]-环己基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-[2’,6’-二异丙基-2-联苯基]-叔丁基膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-双[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2,4,6-三异丙基苯基)苯基]-环己基-[3,5-双(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二苯基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-二叔丁基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-(2-二甲氨基苯基)-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-(4-二甲氨基苯基)-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[2’,6’-二甲氧基-2-联苯基]-正丁基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[2’,6’-二异丙基-2-联苯基]-环己基膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-双[3,5-二(三氟甲基)苯基]膦;
[2,6-双(2-甲氧基-1-萘基)苯基]-[3,5-双(三氟甲基)苯基]-甲基膦;
[2,6-双(2-异丙氧基-1-萘基)苯基]-二苯基膦;
[2,6-双(2-异丙氧基-1-萘基)苯基]-二环己基膦;
[2,6-双(2-甲氧基-6-二甲氨基苯基)苯基]-二苯基膦;
[2,6-双(2-甲氧基-6-二甲氨基苯基)苯基]-二环己基膦;
[2,6-双(2,6-二甲氨基苯基)苯基]-二苯基膦;
[2,6-双(2,6-二甲氨基苯基)苯基]-二环己基膦。
6.根据权利要求1至5项中一项所述的间三联芳单膦配体的制备方法, 其特征是:用4-位带取代基或不带取代基的2,6-二氯苯或2-氟-6-氯苯在丁基锂作用下拔去1-位的氢原子继而发生消去反应形成苯炔类化合物, 再与芳基负离子发生亲核加成反应,而后又发生消去反应可再一次形成苯炔类化合物,再与芳基负离子发生亲核加成反应形成2,6-二芳基苯基负离子,或者用2,6-二芳基苯基溴(碘)为原料与金属锂、正(仲, 叔)丁基锂、金属镁或异丙基格式试剂反应制得2,6-二芳基苯基负离子, 再与PCl3、R2PCl2、R3PCl2或R2R3PCl反应,这里可以加入或不加入CuX1或Pd(PPh3)4, 再根据所加入的氯化磷试剂的种类不同, 选择分步加入R2M和/或R3M (M = li, Na, MgX1, CuX1), X1可以是 Cl, Br或I。
7.根据权利要求1至5项中一项所描述的间三联芳单膦配体所配位的钯络合物, 具有通式II、III、IV、V、VI或VII:
其中
L为权利要求1到5定义的三联芳单膦配体;
X2为Cl、Br、I、甲磺酸基、苯磺酸基、对甲苯磺酸基、甲酸基、乙酸基或苯甲酸基;
R4、R5、R6、R7或R8各自独立地选自H、甲基或苯基。
8.根据权利要求1至5项中一项所述的三联芳单膦配体和元素周期表VIII副族的过渡金属盐或络合物组合形成的体系用作催化剂的用途, 其中, 通常将所述膦配体原位加入到包含了合适的过渡金属前体化合物的反应体系中, 或将所述膦配体先与过渡金属盐或配位络合物搅拌反应形成催化体系然后不经分离提纯直接加入到反应体系中。
9.根据权利要求8 所述的用途, 其特征在于所用的过渡金属是钯、镍、铂、铑、钴、铱和钌。
10.根据权利要求8或9所述的用途, 其特征在于所用的过渡金属络合物是钯或镍络合物, 优选钯络合物。
11.根据权利要求8至10 所述的用途, 其特征在于所述的膦配体用于催化(拟)卤代芳烃联芳烃为底物去形成新的C-C或C-N键的偶联反应中。
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CN113019463A (zh) * | 2021-05-25 | 2021-06-25 | 江苏欣诺科催化剂有限公司 | 钯复合催化剂及其制备方法和应用 |
CN114075257A (zh) * | 2020-08-11 | 2022-02-22 | 成都先导药物开发股份有限公司 | 一种由On-DNA芳基卤代物制备芳胺类化合物的方法 |
CN115066444A (zh) * | 2020-04-24 | 2022-09-16 | Sabic环球技术有限责任公司 | 后茂金属化合物 |
WO2024060641A1 (zh) * | 2022-09-16 | 2024-03-28 | 东莞市均成高新材料有限公司 | 环三联芳膦、它们的制备方法及用途 |
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CN114075257B (zh) * | 2020-08-11 | 2023-08-22 | 成都先导药物开发股份有限公司 | 一种由On-DNA芳基卤代物制备芳胺类化合物的方法 |
CN113019463A (zh) * | 2021-05-25 | 2021-06-25 | 江苏欣诺科催化剂有限公司 | 钯复合催化剂及其制备方法和应用 |
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