CN115385957A - Linear terphenyl aryl phosphine ligand and transition metal complex thereof - Google Patents
Linear terphenyl aryl phosphine ligand and transition metal complex thereof Download PDFInfo
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- CN115385957A CN115385957A CN202110502258.1A CN202110502258A CN115385957A CN 115385957 A CN115385957 A CN 115385957A CN 202110502258 A CN202110502258 A CN 202110502258A CN 115385957 A CN115385957 A CN 115385957A
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- mmol
- group
- dichloromethane
- biphenyl
- added
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 91
- 239000003446 ligand Substances 0.000 title claims abstract description 57
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 48
- 229910052723 transition metal Inorganic materials 0.000 title claims abstract description 13
- 150000003624 transition metals Chemical class 0.000 title claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 title claims description 11
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 title 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 73
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 35
- 238000005859 coupling reaction Methods 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 239000000758 substrate Substances 0.000 claims abstract description 4
- -1 2, 6-dimethylphenyl Chemical group 0.000 claims description 203
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 70
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 49
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 22
- 229910052740 iodine Inorganic materials 0.000 claims description 22
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 10
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 8
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 8
- 230000003197 catalytic effect Effects 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- BLHLJVCOVBYQQS-UHFFFAOYSA-N ethyllithium Chemical compound [Li]CC BLHLJVCOVBYQQS-UHFFFAOYSA-N 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 6
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229910052759 nickel Inorganic materials 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
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- XBEREOHJDYAKDA-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].CC[CH2-] XBEREOHJDYAKDA-UHFFFAOYSA-N 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- DQZLQYHGCKLKGU-UHFFFAOYSA-N magnesium;propane Chemical compound [Mg+2].C[CH-]C.C[CH-]C DQZLQYHGCKLKGU-UHFFFAOYSA-N 0.000 claims description 4
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 101150003085 Pdcl gene Proteins 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 125000000958 aryl methylene group Chemical group 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 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 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 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 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- 125000006713 (C5-C10) cycloalkyl group Chemical group 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 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
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 238000011065 in-situ storage Methods 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
- SZAVVKVUMPLRRS-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].C[CH-]C SZAVVKVUMPLRRS-UHFFFAOYSA-N 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 230000000737 periodic effect Effects 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 239000002243 precursor Substances 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
- 238000000746 purification Methods 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 239000010948 rhodium Substances 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims 1
- 125000005002 aryl methyl group Chemical group 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 150000004696 coordination complex Chemical class 0.000 claims 1
- 150000002681 magnesium compounds Chemical class 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 372
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 94
- 239000012074 organic phase Substances 0.000 description 88
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
- 238000010898 silica gel chromatography Methods 0.000 description 46
- 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 43
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 239000008346 aqueous phase Substances 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 43
- 239000011734 sodium Substances 0.000 description 43
- 238000001035 drying Methods 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- 239000000203 mixture Substances 0.000 description 36
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 34
- 239000007818 Grignard reagent Substances 0.000 description 27
- 150000004795 grignard reagents Chemical class 0.000 description 27
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 description 27
- 239000012298 atmosphere Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 235000010265 sodium sulphite Nutrition 0.000 description 17
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- AKJFBIZAEPTXIL-UHFFFAOYSA-N chloro(dicyclohexyl)phosphane Chemical compound C1CCCCC1P(Cl)C1CCCCC1 AKJFBIZAEPTXIL-UHFFFAOYSA-N 0.000 description 16
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
- 229940045803 cuprous chloride Drugs 0.000 description 15
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 14
- 239000011630 iodine Substances 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 11
- WNCYZVMZKSOPMU-UHFFFAOYSA-N 2-fluoro-1,4-dimethoxybenzene Chemical compound COC1=CC=C(OC)C(F)=C1 WNCYZVMZKSOPMU-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 229910052749 magnesium Inorganic materials 0.000 description 9
- 239000011261 inert gas Substances 0.000 description 8
- 229910000160 potassium phosphate Inorganic materials 0.000 description 8
- 235000011009 potassium phosphates Nutrition 0.000 description 8
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 6
- WKGQNYMQIYJEDX-UHFFFAOYSA-N 2,5-dibromo-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC(Br)=CC(C(C)C)=C1Br WKGQNYMQIYJEDX-UHFFFAOYSA-N 0.000 description 5
- 125000004437 phosphorous atom Chemical group 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical class C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- BKWVXPCYDRURMK-UHFFFAOYSA-N (2,6-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=CC(OC)=C1B(O)O BKWVXPCYDRURMK-UHFFFAOYSA-N 0.000 description 1
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- XUIURRYWQBBCCK-UHFFFAOYSA-N (3,5-dimethoxyphenyl)boronic acid Chemical compound COC1=CC(OC)=CC(B(O)O)=C1 XUIURRYWQBBCCK-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- IVUHTLFKBDDICS-UHFFFAOYSA-N (4-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=C(B(O)O)C=C1 IVUHTLFKBDDICS-UHFFFAOYSA-N 0.000 description 1
- VEZJOZSIGSNYEB-UHFFFAOYSA-N 1,2-dibromo-3,4,5,6-tetramethylbenzene Chemical compound CC1=C(C)C(C)=C(Br)C(Br)=C1C VEZJOZSIGSNYEB-UHFFFAOYSA-N 0.000 description 1
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 1
- HJOZSJXZWZNSTJ-UHFFFAOYSA-N 1-bromo-3,5-di(propan-2-yloxy)benzene Chemical compound CC(C)OC1=CC(Br)=CC(OC(C)C)=C1 HJOZSJXZWZNSTJ-UHFFFAOYSA-N 0.000 description 1
- MOGQNVSKBCVIPW-UHFFFAOYSA-N 1-methylpyrazol-3-amine Chemical compound CN1C=CC(N)=N1 MOGQNVSKBCVIPW-UHFFFAOYSA-N 0.000 description 1
- XCMISAPCWHTVNG-UHFFFAOYSA-N 3-bromothiophene Chemical compound BrC=1C=CSC=1 XCMISAPCWHTVNG-UHFFFAOYSA-N 0.000 description 1
- XHZWFUVEKDDQPF-UHFFFAOYSA-N 5-bromo-1h-pyrazole Chemical compound BrC1=CC=NN1 XHZWFUVEKDDQPF-UHFFFAOYSA-N 0.000 description 1
- FTFFHWWIPOQCBC-UHFFFAOYSA-N 5-bromopyridine-3-carbonitrile Chemical compound BrC1=CN=CC(C#N)=C1 FTFFHWWIPOQCBC-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 238000005577 Kumada cross-coupling reaction Methods 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- MCRSZLVSRGTMIH-UHFFFAOYSA-N ditert-butyl(chloro)phosphane Chemical compound CC(C)(C)P(Cl)C(C)(C)C MCRSZLVSRGTMIH-UHFFFAOYSA-N 0.000 description 1
- QMLPJDVGNRHGJQ-UHFFFAOYSA-N ditert-butyl-(1-methyl-2,2-diphenylcyclopropyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1(C)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 QMLPJDVGNRHGJQ-UHFFFAOYSA-N 0.000 description 1
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940096017 silver fluoride Drugs 0.000 description 1
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5022—Aromatic phosphines (P-C aromatic linkage)
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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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- 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
- C07D213/60—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 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
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- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
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- 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
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Abstract
The invention provides a linear terpyridylphosphine ligand and a transition metal complex thereof, and provides a linear terpyridylphosphine ligand and a preparation method thereof; the invention also provides a linear tris-biaryl phosphine ligand coordinated palladium complex and its use in catalyzing coupling reactions in which a (pseudo) halogenated aromatic hydrocarbon is one of the substrates.
Description
Technical Field
The present invention relates to novel linear tris-biarylphosphine ligands (including P-chirality), processes for their preparation, their use as key components and catalytic systems consisting of late transition metals, and their use in palladium catalysed organic reactions, particularly in catalysed coupling reactions, including C-C and C-X bond formation reactions.
Background
Among the many organic reactions catalyzed by transition metals, the coupling reaction is a very important class of reactions. Therefore, the development of efficient chiral or achiral phosphine ligands to achieve efficient catalytic coupling reactions is receiving attention. The following chemical structural formula lists several kinds of organic phosphine ligands with rich electrons and large steric hindrance, which are used for palladium catalytic coupling reaction and have excellent performance, and the organic phosphine ligands are monodentate phosphine ligands. Fu et al found that electron rich, highly sterically hindered tri-tert-butylphosphine has excellent properties in Pd-catalyzed coupling reactions, raising the hot tide for the development of this new class of phosphine ligands (a.f. Littke, et al, j.am. Chem. Soc.,2000, 122, 4020). Electron-rich, highly sterically hindered diamantaylphosphine (M. Beller, et al., CN 101195641) and polysubstituted phenylferrocenylphosphinanes QPhos (J.F. Hartwig, et al., WO 2002/011883) have been developed by Beller in Germany and Hartwig in Yale university, respectively, and have become commercial products. The japanese Takasago company developed phosphine ligands (cBRIDP) with aryl cyclopropyl skeletons (k.suzuki, et al, WO 2013/032035), although Hiyashi et al have long discovered bis-aryl phosphines, such as 1,1' -binaphthyl-2-phosphines, to have superior catalytic properties in palladium-catalyzed Kumada coupling reactions, buchwald et al extended to bis-phenyl phosphines, and developed a series of bis-phenyl phosphines with superior properties (s.l. Buchwald, et al, US6, 307, 087; WO 2009/076622). And the tripartite arylphosphine ligand of the invention has benzene rings on both sides of a phosphorus atom, so that one benzene ring B of lone pair electrons on the phosphorus atom can be oriented, and the defect of conformation torsion of the bipartite arylphosphine of Buchwald and the like can be overcome (CN 110240616B).
To obtain high performance coupled phosphine ligands, it is a common strategy to introduce large groups such as cyclohexyl, tert-butyl and even adamantyl on the phosphorus atom, but since the phosphorus atom is SP 3 Hybridization, the direction of the introduced substituent is opposite to the direction of the metal center coordinated with the substituent, and the introduced substituent can be regarded as only controlling the space on one side of the Pd center, as shown in R in the following chemical structural formula 7 And R 8 And (4) a substituent. According to the invention, 2 aryl groups (benzene ring B is substituted by 4) are introduced into 4-position of benzene ring B, so that the effect of introducing substituent groups into the other side of the Pd center is achieved, the substituent groups are arranged around the Pd center, the steric hindrance around the Pd center can be better regulated and controlled, and the high-performance catalyst is obtained.
Summary of The Invention
The present invention relates to: (1) a linear tris-biaryl phosphine ligand; (2) a preparation method of a linear terpyridylphosphine ligand; (3) a linear tris-biaryl phosphine ligand coordinated palladium complex; (4) A catalytic system combining a linear tris-biaryl phosphine ligand and palladium comprises a palladium complex coordinated by the linear tris-biaryl phosphine ligand and application of the palladium complex in catalyzing a coupling reaction taking (pseudo) halogenated aromatic hydrocarbon as a substrate.
DISCLOSURE OF THE INVENTION
In a first aspect, the present invention provides phosphine ligands having the general formula I,
wherein R is 1 、R 2 、R 3 And R 4 Each independently selected from H, (C1-C10) alkyl, (C6-C20) aryl, [ O (C1-C10)]Alkoxy and [ N (C1-C10) 2 ]A dialkylamino group. R is 5 And R 6 Each independently selected from (C1-C10) alkyl, [ O (C1-C10)]Alkoxy, [ O (C6-C10)]Aryloxy and [ N (C1-C10) 2 ]A dialkylamino group. R 7 And R 8 Each independently selected from the group consisting of (C1-C20) alkyl, (C3-C10) cycloalkyl, (5-11 membered) heterocycloalkyl, (C6-C20) aryl, (C4-C20) heteroaryl, (C7-C20) arylmethylene and (C9-C35) 2-linked (hetero) aryl, where (C3-C10) cycloalkyl, (5-11 membered) heterocycloalkyl, (C6-C20) aryl, (C4-C20) heteroaryl, (C7-C20) arylmethylene and (C9-C35) 2-linked (hetero) aryl may have 1 to 3 heteroatoms independently selected from F, (C1-C10) alkyl which may have heteroatoms, (C5-C10) cycloalkyl which may have heteroatoms and (C6-C20) aryl, wherein the heteroatoms in the heteroaryl and 2-linked (hetero) aryl are selected from the group consisting of O, N and S atoms, and the heteroatoms in the substituents are F, O, S, N and Si. Ar is selected from phenyl, naphthyl and anthryl which may have a substituent(s) such as (C1-C10) alkyl, (C3-C10) cycloalkylA (C6-C20) aryl group, a [ O (C1-C10)]Alkoxy group of [ O (C6-C10) ]]Aryloxy group of [ N (C1-C10) ] 2 ]And (C6-20) an aryl group.
Ar in the present invention may be further selected from the following groups, but it is not intended that the following groups limit the present invention: phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2, 6-dimethylphenyl group, 3, 5-dimethylphenyl group, 2,4, 6-trimethylphenyl group, 2,3,4,5, 6-pentamethylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2, 6-diethylphenyl group, 3, 5-diethylphenyl group, 2,4, 6-triethylphenyl group, 2-isopropylphenyl group, 3-isopropylphenyl group, 4-butylphenyl group, 2, 6-diisopropylphenyl group, 3, 5-diisopropylphenyl group, 2,4, 6-triisopropylphenyl group, 2-sec-butylphenyl group, 2, 6-di-sec-butylphenyl group, 2,4, 6-tri-sec-butylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-butoxyphenyl group, 2, 6-dimethoxyphenyl group, 3, 5-dimethoxyphenyl group, 2,4, 6-trimethoxyphenyl group, 2-phenoxyphenyl group, 3-phenoxyphenyl group, 4-trifluoromethylphenyl group, 6-phenoxyphenyl group, 2-phenoxyphenyl group, 3-methoxyphenyl group, 3-trifluoromethylphenyl group, 3-isopropoxyphenyl group, 2, 3-trifluoromethylphenyl group, 3, 5-trifluoromethylphenyl group, 5-isopropoxyphenyl group, 2,3, 6-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 5-trifluoromethylphenyl group, 6-trifluoromethylphenyl group, 3-isopropoxyphenyl group, 2, 4-trifluoromethylphenyl group, and the like, 3-dimethylaminophenyl group, 1-naphthyl group, 2-methoxy-1-naphthyl group, 2-phenoxy-1-naphthyl group, 2-isopropoxy-1-naphthyl group, 9-anthracenyl group, 10-methoxy-9-anthracenyl group, 10-nitro-9-anthracenyl group, 10-nitrile-9-anthracenyl group and 10-dimethylamino-9-anthracenyl group.
In the invention, R 5 And R 6 The following groups may be further selected from, but are not meant to limit the invention: each independently selected from the group consisting of methyl, ethyl, isopropyl, sec-butyl, methoxy, ethoxy, isopropoxy, phenoxy and dimethylamino.
In the invention, R 7 And R 8 May further each independently be further selected from the following groups, but the following groups are not meant to beThe cliques limit the invention: selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, cyclopentyl, cyclohexyl, adamantyl, phenyl, 2-methylphenyl, 2-isopropylphenyl, 2-methoxyphenyl, 2- (dimethylamino) phenyl, 4-methylphenyl, 4-fluorophenyl, 4-methoxyphenyl, 4- (dimethylamino) phenyl, 3, 5-dimethylphenyl, 3, 5-bis (trifluoromethyl) phenyl, 3, 5-difluorophenyl, 3, 5-di-t-butylphenyl, 2, 6-dimethylphenyl, 2, 6-dimethoxyphenyl, 2, 6-diisopropylphenyl, 2,4, 6-trimethoxyphenyl, 2-biphenyl, 2',6' -dimethyl-2-biphenyl, 2',6' -dimethoxy-2-biphenyl, 2',6' -diisopropoxy-2-biphenyl, 2',6' -bisdimethylamino-2-biphenyl, 2',6' -diisopropyl-2-biphenyl, 2',4',6' -triisopropyl-2-biphenyl, 2-furyl, 2-thienyl, 2-benzofuryl, 2-benzothienyl, 2-pyridyl, 2-tetrahydrofuryl, 3-phenyl-2-furyl, 3-phenyl-2-thienyl, 3- (2, 6-dimethylphenyl) -2-furyl, 3- (2, 6-dimethylphenyl) -2-thienyl, 2' -diisopropoxy-2-biphenyl, 2',6' -dimethylfuryl, 2' -thienyl, 3- (2, 6-dimethoxyphenyl) -2-furyl, 3- (2, 6-dimethoxyphenyl) -2-thienyl, 3- (2, 4, 6-triisopropylphenyl) -2-furyl and 3- (2, 4, 6-triisopropylphenyl) -2-thienyl.
In a second aspect, the present invention provides a process for the preparation of a phosphine ligand as defined in the preceding claims. The compounds of the general formulae III and IV are reacted in the presence of bases or metals to form compounds of the general formula II,
wherein: x 1 Br, I, li, mgCl, mgBr or MgI. X 2 、X 3 And X 4 Each independently selected from H, F, cl, br or I. R is 1 、R 2 、R 3 、R 4 、R 5 、R 6 And Ar is as defined above. When X is present 1 When Br or I is used, II is firstly butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium, ethyl lithium, propyl lithium, isopropyl magnesium bromide, isopropyl magnesium chloride, diisopropyl magnesium, metal magnesium or metal lithium transShould be such that X 1 Conversion to Li, mgCl, mgBr or MgI. For compounds having the structure of formula III, when X 4 In the case of Cl, br or I, IV is reacted with butyllithium, sec-butyllithium, tert-butyllithium, methyllithium, ethyllithium, propyllithium, isopropyllithium, isopropylmagnesium bromide, isopropylmagnesium chloride, diisopropylmagnesium, magnesium metal or lithium metal, so that X 4 Conversion to Li, mgCl, mgBr or MgI. When X is present 4 Is H and R 5 And R 6 When both are alkoxy or phenoxy, IV is reacted with butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium or ethyl lithium to give X 4 To become a lithium compound of Li. Using known techniques, X in the general formula III 2 And X 3 Eliminating the formation of corresponding alkynide, reacting with lithium or magnesium IV compound, and adding Br 2 Or I 2 To obtain the bromide or iodide of II. When X in II 1 In the case of Li, mgCl, mgBr or MgI, with PCl 3 、R 7 PCl 2 、R 8 PCl 2 Or R 7 R 8 PCl reaction, with or without addition of metered or catalytic amounts of LiCl, liBr, cuCl, cuBr, cuI, pd (PPh) 3 ) 4 Or PdCl 2 (PPh 3 ) 2 And then the step-by-step addition of R is selected according to the different types of the added phosphorus chloride reagent 7 M and/or R 8 The type and quantity of M, wherein M is Li, na, mgCl, mgBr, mgI, cuCl, cuBr or CuI.
When CuCl, cuBr, cuI and Pd (PPh) are added 3 ) 4 Or PdCl 2 (PPh 3 ) 2 Sometimes, it is beneficial to add a complexing agent such as ethylenediamine or ammonia to remove the metal salt, which can improve yield, especially when metered amounts of metal salt are added.
The reaction solvent is selected from one of benzene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, tert-butyl methyl ether and diphenyl ether or the mixture of the benzene, the xylene, the tetrahydrofuran, the 2-methyltetrahydrofuran, the dioxane and the tert-butyl methyl ether.
In a third aspect, the present invention also provides a palladium complex coordinated by a phosphine ligand as defined in the preceding claims, having the general structures of formulae V, VI, VII, VIII, IX, X and XI.
Wherein L is a phosphine ligand as defined in claims 1 to 5; x 5 、X 6 、X 7 、X 8 、X 9 And X 10 Is Cl - 、Br - 、I - Mesylate, triflate, benzenesulfonate, p-toluenesulfonate, formate, acetate, trifluoroacetate or benzoate; r is 9 、R 10 、R 11 、R 12 、R 13 And R 14 Each independently selected from H, methyl or phenyl.
In a fourth aspect, the present invention also provides the use of the invented system of a phosphine ligand in combination with a transition metal salt or complex of subgroup VIII of the periodic table of elements as a catalyst, wherein the phosphine ligand may be added in situ to a reaction system comprising a suitable transition metal precursor compound, and advantageously first prepared as a transition metal coordination complex. The transition metal herein is preferably palladium, nickel, platinum, rhodium, cobalt, iridium and ruthenium, and more preferably palladium or nickel.
The invention provides the use of the invented phosphine ligands as support ligands in coupling reactions in which palladium and nickel catalyse (pseudo) halogenated arene as one of the substrates to form new C-C, C-N, C-O or C-F bonds.
Detailed Description
The following examples are intended to specifically illustrate the present invention, but the present invention is not limited to the following examples. In the following synthesis examples, the operation was carried out in a high-purity nitrogen atmosphere, and the solvent used was dehydrated and deoxygenated, unless otherwise specified.
Example 1:2, 6-diisopropyl-4- (2-methoxyphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-dibromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 2-methoxyphenylboronic acid (6.84 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol) and [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) Methylbenzenesulfonate](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 9.89 g of a product with a yield of 95%.
Grignard reagent was prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropyl-4- (2-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1), and 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise to the solution in THF (30.0 mL) and refluxed at 70 ℃ for 12 hours in an oil bath. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-methoxyphenyl) -2' -iodobiphenyl (4.70 g, 10.0 mmol 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M in hexane, 11.0 mmol) and reacted at this temperature for 1 h, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), the cold bath was allowed to warm to room temperature and refluxed at 90 deg.C in an oil bath for 12 h. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 50 mL of saturated sodium chloride solution, and the aqueous phase is extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 Drying, concentrating under reduced pressure, separating and purifying the residue by silica gel column chromatography (petroleum ether)Ethyl acetate = 7) to obtain 3.13 g of product with a yield of 58%.
31 P NMR (162 MHz, CDCl 3 ) δ: -13.7。
Example 2:2, 6-diisopropyl-4- (3-methoxyphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-dibromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 3-methoxyphenylboronic acid (6.84 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol) and [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta.2-C, N) palladium (II) methylbenzenesulfonate were put into a glove box](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 10.20 g of a product with a yield of 98%.
Grignard reagent was prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropyl-4- (3-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1), and 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise to the solution in THF (30.0 mL) and refluxed at 70 ℃ for 12 hours in an oil bath. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 7.80 g of a product with a yield of 83%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3-methoxyphenyl) -2' -iodoniumBenzene (4.70 g, 10.0 mmol 1) and tetrahydrofuran (30.0 mL) were cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) were added, the reaction was allowed to proceed at this temperature for 1 h, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the bath was removed and allowed to spontaneously warm to room temperature, and the mixture was refluxed in an oil bath at 90 deg.C for 12 h. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 50 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 3.41 g of a product with a yield of 63%.
31 P NMR (162 MHz, CDCl 3 ) δ: -12.9。
Example 3: :2',6' -diisopropyl-4 ' - (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added, and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-methoxyphenyl) -2' -iodonium-3',6' -Dimethoxybiphenyl (5.30 g, 10.0 mmol) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) were added, reacted at this temperature for 1 h, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the cold bath was removed and allowed to warm to room temperature, and the mixture was refluxed in an oil bath at 90 deg.C for 12 h. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 50 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: -2.6。
Example 4:2',6' -diisopropyl-4 ' - (3-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (3-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, added with 8.8 mL of n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, added with the Grignard reagent at this temperature, reacted for 1 h, and then the cold bath was removed and allowed to naturally warm to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3-methoxy)Phenylphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.30 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL) were cooled to-78 deg.C, 4.4 mL of n-butyllithium (2.5M n-hexane solution, 11.0 mmol) were added, reacted at this temperature for 1 h, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the cold bath was removed and allowed to naturally warm to room temperature, and refluxed at 90 deg.C in an oil bath for 12 h. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 50 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: -2.1。
Example 5: :2',6' -diisopropyl-4 ' - (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-di-tert-butylphosphine
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-methoxyphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.30 g, 10.0 mmol), tetrahydrofuran (30.0 mL), and toluene (100 mL), cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M in hexane, 11.0 mmol) was added, reacted at this temperature for 1 h, cuprous chloride (0.50 g, 5.0 mmol) was added to the two-necked flask, di-t-butylphosphine (1.99 g, 11.0 mmol) was added, the cold bath was allowed to naturally rise to room temperature, and the oil bath was refluxed at 100 deg.C for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: 33.6。
Example 6:2',6' -diisopropyl-4 ' - (3-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-di-tert-butylphosphine
2, 6-diisopropyl-4- (3-methoxyphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.30 g, 10.0 mmol 1), tetrahydrofuran (30.0 mL) and toluene (100 mL) were added to a dry 100 mL two-necked flask, cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) was added, reacted at this temperature for 1 h, cuprous chloride (1.00 g, 10.0 mmol 1) was added to the two-necked flask, di-t-butylchlorophosphine (1.99 g, 11.0 mmol) was added, the cold bath was removed and allowed to spontaneously rise to room temperature, and refluxed at 100 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: 33.7。
Example 7:2',6' -diisopropyl-4 ' - (2-fluorophenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2-fluorophenyl) bromobenzene (6.70 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooling to 0 deg.C, addingIodine (5.08 g,20.0 mmol), and the addition was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-fluorophenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.18 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to naturally warm to room temperature, and refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7.
31 P NMR (162 MHz, CDCl 3 ) δ: -5.6。
Example 8:2',6' -diisopropyl-4 ' - (3-fluorophenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (3-fluorophenyl) bromobenzene (6.70 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, and reacted at 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol) for 1 h at which temperatureAdding the Grignard reagent, reacting for 1 h, removing the cold bath, naturally heating to room temperature, and reacting for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added, and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 4.66 g of a product with a yield of 45%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3-fluorophenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.18 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to naturally warm to room temperature, and refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 4.06 g of a product in 69% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: -6.3。
Example 9:2',6' -diisopropyl-4 ' - (2-trifluoromethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2-trifluoromethylphenyl) bromobenzene (7.70 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmo 1) and tetrahydrofuran (R) ((R))50.0 mL), cooled to-78 deg.C, added with 8.8 mL of n-butyllithium (2.5M n-hexane solution, 22.0 mmol), reacted at this temperature for 1 h, added with the above Grignard reagent at this temperature, reacted for 1 h, removed from the cooling bath and naturally warmed to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 3.18 g of a product with a yield of 28%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-trifluoromethylphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.68 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, added with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to warm to room temperature, and refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 2.94 g of a product with a yield of 46%.
31 P NMR (162 MHz, CDCl 3 ) δ: -7.3。
Example 10:2',6' -diisopropyl-4 ' - (3-trifluoromethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (3-trifluoromethylphenyl) bromobenzene (7.70 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 4.20 g of a product with a yield of 37%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3-trifluoromethylphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.68 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to warm to room temperature, and refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 3.32 g of a product with a yield of 52%.
31 P NMR (162 MHz, CDCl 3 ) δ: -7.8。
Example 11:2, 6-diisopropyl-4- (2-methylphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-twoBromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 2-methylphenylboronic acid (6.12 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol) and palladium [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta.2-C, N) methylphenylsulfonate (II)](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
Grignard reagent was prepared from magnesium turnings (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropyl-4- (2-methylphenyl) bromobenzene (6.62 g,20.0 mmo 1), and 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise in THF (30.0 mL) and refluxed at 70 ℃ for 12 hours in an oil bath. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 8.26 g of a product with a yield of 91%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-methylphenyl) -2' -iodobiphenyl (4.54 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, added with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, added with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), the bath was allowed to warm to room temperature naturally, and refluxed at 90 deg.C for 12 h in an oil bath. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8.
31 P NMR (162 MHz, CDCl 3 ) δ: -14.5。
Example 12:2, 6-diisopropyl-4- (3-methylphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-dibromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 3-methylphenylboronic acid (6.12 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol) and [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta.2-C, N) palladium (II) methylphenylsulfonate](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
Grignard reagent was prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropyl-4- (3-methylphenyl) bromobenzene (6.62 g,20.0 mmo 1), and 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise to the solution in THF (30.0 mL) and refluxed in an oil bath at 70 ℃ for 12 hours. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 8.44 g of a product with a yield of 93%.
One trunkA dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3-methylphenyl) -2' -iodobiphenyl (4.54 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), the bath was allowed to warm to room temperature and refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8.
31 P NMR (162 MHz, CDCl 3 ) δ: -15.2。
Example 13:2, 6-diisopropyl-4- (2, 6-dimethoxyphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-dibromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 2, 6-dimethoxyphenylboronic acid (8.19 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.14 g, 0.3 mmol) and [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta.2-C, N) palladium (II) methylbenzenesulfonate were put into a glove box](0.26 g, 0.3 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 9.84 g of a product with a yield of 87%.
Prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisoPropyl-4- (2, 6-dimethoxyphenyl) bromobenzene (7.54 g,20.0 mmo 1) was prepared as Grignard reagent, 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise in THF (30.0 mL) and refluxed for 12 h at 70 ℃ in an oil bath. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2, 6-dimethoxyphenyl) -2' -iodobiphenyl (5.00 g, 10.0 mmo 1) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M in hexane, 11.0 mmol) was added, reacted at this temperature for 1 h, cuprous chloride (1.00 g, 10.0 mmo 1) was added to the two-necked flask, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the bath was allowed to warm to room temperature and refluxed at 90 deg.C for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: -13.8。
Example 14:2, 6-diisopropyl-4- (3, 5-dimethoxyphenyl) -2' -biphenyl-dicyclohexylphosphine
In a glove box, 1, 4-dibromo-2, 6-diisopropylbenzene (9.60 g, 30.0 mmol), 3, 5-dimethoxyphenylboronic acid (8.19 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol), and[ (2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl) (2' -methylaminobiphenyl-2-yl-. Eta.2-C, N) palladium (II) methylbenzenesulfonate)](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 10.40 g of a product in 92% yield.
Grignard reagent was prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropyl-4- (3, 5-dimethoxyphenyl) bromobenzene (7.54 g,20.0 mmo 1), and 2-bromochlorobenzene (3.83 g,20.0 mmol) was added dropwise in THF (30.0 mL) and refluxed in an oil bath at 70 ℃ for 12 hours. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 8.93 g of a product with a yield of 89%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3, 5-dimethoxyphenyl) -2' -iodobiphenyl (5.00 g, 10.0 mmo 1) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, charged with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), the bath was allowed to warm to room temperature and refluxed at 90 deg.C for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 3.20 g of a product with a yield of 56%.
31 P NMR (162 MHz, CDCl 3 ) δ: -12.9。
Example 15: :2',6' -diisopropyl-4 ' - (2, 6-dimethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2, 6-dimethylphenyl) bromobenzene (6.90 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10).
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2, 6-dimethylphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.28 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, added with 4.4 mL n-butyllithium (2.5M in hexane, 11.0 mmol), reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1), added with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to naturally warm to room temperature with the cold bath removed, and refluxed at 90 deg.C for 12 h in an oil bath. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are treated with Na 2 SO 4 After dryingConcentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: -4.5。
Example 16: 2',6' -diisopropyl-4 ' - (3, 5-dimethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine
Grignard reagent was prepared from magnesium chips (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (3, 5-dimethylphenyl) bromobenzene (6.90 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooled to 0 deg.C, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 4.01 g of a product with a yield of 38%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (3, 5-dimethylphenyl) -2' -iodo-3 ',6' -dimethoxybiphenyl (5.28 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, added with 4.4 mL n-butyllithium (2.5M in hexane, 11.0 mmol), reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1), added with dicyclohexylchlorophosphine (2.56 g, 11.0 mmol), allowed to naturally warm to room temperature with the cold bath removed, and refluxed at 90 deg.C for 12 h in an oil bath. Adding 40 mL ammonia (26.0% -28.0%) and stirring for 50 min, extracting with dichloromethane three times (300 mL), and adding 50 mL organic phaseThe saturated sodium chloride solution was washed and the aqueous phase was extracted three more times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: -3.9。
Example 17: 2',6' -diisopropoxy-4 ' - (2-methylphenyl) -2-biphenyl-3, 4,5, 6-tetramethyl-dicyclohexylphosphine
In a glove box, 3, 5-diisopropoxybromobenzene (8.19 g, 30.0 mmol), 2-methylphenylboronic acid (6.12 g, 45.0 mmol), potassium phosphate (19.08 g, 90.0 mmol), 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl (0.07 g, 0.15 mmol) and palladium [ (2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl) (2 ' -methylaminobiphenyl-2-yl-. Eta.2-C, N) methylphenylsulfonate (II)](0.13 g, 0.15 mmol) and 90 mL of anhydrous tetrahydrofuran were placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 100 ℃ for 12 hours. It is extracted three times with dichloromethane (300 mL), the organic phase is washed with 80 mL of saturated sodium chloride solution, and the aqueous phase is extracted three more times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 7.92 g of a product with a yield of 93%.
A dry 250 mL two-necked flask was charged with 3, 5-diisopropoxy-2' -methylbiphenyl (14.20 g, 50.0 mmo 1) and n-hexane (100.0 mL), 22.0 mL of n-butyllithium (2.5M in n-hexane, 55.0 mmol) was added, and the oil bath was refluxed at 80 ℃ for 2 h. Cooled to 0 deg.C, liquid bromine (8.00 g, 50.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 Drying, concentrating under reduced pressure, and performing silica gel column chromatography on the residueSeparation and purification (petroleum ether: ethyl acetate = 10).
Grignard reagent was prepared from magnesium chips (0.97 g,40.0 mmo 1), THF (50.0 mL) and 2, 6-diisopropoxy-4- (2-methylphenyl) bromobenzene (7.26 g,20.0 mmo 1), and 1, 2-dibromo-3, 4,5, 6-tetramethylbenzene (5.84 g,20.0 mmol) was dissolved in THF (40.0 mL) dropwise and refluxed at 70 ℃ for 12 hours in an oil bath. After cooling to room temperature, iodine (5.08 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10 = 1) to obtain 9.45 g of a product with a yield of 87%.
A dry 100 mL two-necked flask was charged with 2',6' -diisopropoxy-4 ' - (2-methylphenyl) -2-iodo-3, 4,5, 6-tetramethylbiphenyl (5.43 g, 10.0 mmo 1) and tetrahydrofuran (30.0 mL), cooled to-78 deg.C, 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) was added, reacted at this temperature for 1 h, cuprous chloride (1.00 g, 10.0 mmo 1) was added to the two-necked flask, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the bath was allowed to warm to room temperature, and the mixture was refluxed at 90 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, concentration was performed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8.
31 P NMR (162 MHz, CDCl 3 ) δ: 15.2。
Example 18: :2',6' -diisopropyl-4 ' - (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-diamondylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with 1, 4-dimethoxy-2-fluorobenzene (3.12 g,20.0 mmol) and tetrahydrofuran (50.0 mL), cooled to-78 deg.C, charged with 8.8 mL n-butyllithium (2.5M in n-hexane, 22.0 mmol), reacted at this temperature for 1 h, charged with the above Grignard reagent at this temperature, reacted for 1 h, and the cold bath was removed and allowed to spontaneously rise to room temperature for 12 h. Cooled to 0 deg.C, liquid bromine (3.18 g,20.0 mmol) was added and the reaction was completed for 30 minutes. The reaction solution was washed with sodium sulfite solution and extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (90 mL). The combined organic phases are treated with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 7 = 1) to obtain 3.96 g of a product with a yield of 41%.
A dry 100 mL two-necked flask was charged with 2, 6-diisopropyl-4- (2-methoxyphenyl) -2' -bromo-3 ',6' -dimethoxybiphenyl (4.83 g, 10.0 mmo 1) and tetrahydrofuran (20.0 mL), cooled to-78 deg.C, charged with 4.4 mL n-butyllithium (2.5M n-hexane solution, 11.0 mmol) and reacted at this temperature for 1 h, added with cuprous chloride (1.00 g, 10.0 mmo 1) to the two-necked flask, added with dimonochlorophosphine (3.71 g, 11.0 mmol), removed from the cold bath and allowed to rise to room temperature, charged with 150 mL of toluene, and refluxed at 140 deg.C in an oil bath for 12 h. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5.
31 P NMR (162 MHz, CDCl 3 ) δ: 35.4。
Example 19: : {2, 6-bis [2, 6-diisopropyl-4- (2-methoxyphenyl) phenyl ] phenyl } -dicyclohexylphosphine
Grignard reagent was prepared from magnesium turnings (0.49 g,20.0 mmo 1), THF (50.0 mL), and 2, 6-diisopropyl-4- (2-methoxyphenyl) bromobenzene (6.94 g,20.0 mmo 1).
A dry 250 mL two-necked flask was charged with m-dichlorobenzene (1.47 g, 10.0 mmol) and THF (15 mL). After cooling to-85 deg.C, 4.8 mL of n-butyllithium (2.5M in hexane, 12.0 mmol) was added and the reaction stirred for 2 h, the preparative Grignard reagent was transferred to a two-necked flask through a double needle tip. The cooling bath is removed, the temperature is naturally raised to the room temperature, and the mixture is refluxed for 12 hours at the temperature of 70 ℃ in an oil bath. Cuprous chloride (1.00 g, 10.0 mmo 1) was added to the two-necked flask, dicyclohexylchlorophosphine (2.56 g, 11.0 mmol) was added, the cold bath was removed and the temperature was naturally raised to room temperature, and then the mixture was refluxed at 90 ℃ in an oil bath for 12 hours. 40 mL of aqueous ammonia (26.0% -28.0%) was added and stirred for 50 min, extracted three times with dichloromethane (300 mL), the organic phase was washed with 50 mL of saturated sodium chloride solution, and the aqueous phase was extracted three times with dichloromethane (50 mL). The combined organic phases are washed with Na 2 SO 4 After drying, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8.
31 P NMR (162 MHz, CDCl 3 ) δ: 8.7。
Example 20, 6-diisopropyl-4- (2-methoxyphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium (II) chloride
Add phosphine ligand (540.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) palladium chloride to a dry 50 mL Stirling flask under inert atmosphere] 2 (310.0 mg, 0.5 mmol) and 5 mL of dichloromethane, the reaction was stirred for 6 h. The solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane), whereby 0.83 g of a yellow solid was obtained in 97% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 33.2。
Example 21:2, 6-diisopropyl-4- (3-methoxyphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) chloride
Add phosphine ligand (540.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) Palladium chloride to a dry 50 mL Schlenk flask under inert atmosphere] 2 (310.0 mg, 0.5 mmol) and 5 mL of dichloromethane were stirred for 6 h, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.82 g of a yellow solid in 96% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 33.1。
Example 22:2',6' -diisopropyl-4 '- (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (600.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.98 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 39.8。
Example 23:2',6' -diisopropyl-4 '- (3-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium (II) Methylbenzenesulfonate
Add phosphine ligand (600 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.98 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 39.2。
Example 24:2',6' -diisopropyl-4 '- (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-di-tert-butylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) 2 -C, N) Palladium (II) Methylbenzenesulfonate
To a dry 50 mL Schlenk bottle, phosphine ligand (549.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate were added under inert gas atmosphere] 2 (383.0 mg, 0.5 mmol), and 5 mL dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.87 g of a yellow solid in 93% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 69.3。
Example 25:2',6' -diisopropyl-4 '- (3-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-di-tert-butylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) 2 -C, N) Palladium (II) Methylbenzenesulfonate
To a dry 50 mL Schlenk bottle, phosphine ligand (549.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate were added under an inert gas atmosphere] 2 (383.0 mg, 0.5 mmol), and 5 mL of dichloromethane, and stirringAfter 6 h, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane), to give 0.82 g of a yellow solid in 88% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 70.1。
Example 26:2',6' -diisopropyl-4 '- (2-fluorophenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (589.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.97 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 45.2。
Example 27:2',6' -diisopropyl-4 '- (3-fluorophenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium (II) Methylbenzenesulfonate
Add phosphine ligand (589.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.97 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 44.9。
Example 28:2',6' -diisopropyl-4 ' - (2-trifluoromethyl)Phenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (639.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol), and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.76 g of a yellow solid in 74% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 46.2。
Example 29:2',6' -diisopropyl-4 '- (3-trifluoromethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (639.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol), and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.83 g of a yellow solid in 81% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 43.3。
Example 30:2, 6-diisopropyl-4- (2-methylphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) chloride
Under the inert gas atmosphere, the reaction kettle is filled with inert gas,into a dry 50 mL Schlenk bottle, phosphine ligand (525.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) palladium chloride were added] 2 (310.0 mg, 0.5 mmol) and 5 mL of dichloromethane were stirred for 6 hours, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.83 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 32.9。
Example 31:2, 6-diisopropyl-4- (3-methylphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) chloride
Add phosphine ligand (525.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) palladium chloride to a dry 50 mL Schlenk flask under inert atmosphere] 2 (310.0 mg, 0.5 mmol) and 5 mL of dichloromethane were stirred for 6 hours, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.83 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 33.1。
Example 32, 6-diisopropyl-4- (2, 6-dimethoxyphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium (II) chloride
Add phosphine ligand (571.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) palladium chloride to a dry 50 mL Schlenk flask under inert atmosphere] 2 (310.0 mg, 0.5 mmol) and 5 mL of dichloromethane were stirred for 6 hours, the solvent was removed by concentration under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.88 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 43.2。
Example 33:2, 6-diisopropyl-4- (3, 5-dimethoxyphenyl) -2 '-biphenyl-dicyclohexylphosphine (2' -aminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) chloride
Add phosphine ligand (571.0 mg, 1.0 mmol) and [ (2' -aminobiphenyl-2-yl-C, N) palladium chloride to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol), and 5 mL dichloromethane, stirring for 6 h, concentrating under reduced pressure to remove solvent, and purifying the residue by silica gel column chromatography (eluting with dichloromethane) to obtain yellow solid 0.88 g, yield 99%.
31 P NMR (162 MHz, CDCl 3 ) δ: 43.1。
Example 34:2',6' -diisopropyl-4 '- (2, 6-dimethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta. 2 -C, N) Palladium (II) Methylbenzenesulfonate
Add phosphine ligand (599.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.98 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 39.8。
Example 35:2',6' -diisopropyl-4 '- (3, 5-dimethylphenyl) -2-biphenyl-3, 6-dimethoxy-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (599.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 0.98 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 42.3。
Example 36: [ 2.6-diisopropyl-3, 5-bis (2-methoxyphenyl) yl-3 ',6' -dimethoxy-2 ' -biphenyl-dicyclohexylphosphine ] yl-palladium (II) chloride
To a dry 50 mL Schlenk flask, 2 phosphine ligand (599, 1.0 mmol) and allyl palladium (II) chloride dimer (180.0 mg, 0.5 mmol), and 3 mL methylene chloride were added under an inert gas atmosphere, and the mixture was stirred for 6 hours, concentrated under reduced pressure to remove the solvent, and the residue was purified by silica gel column chromatography (methylene chloride) to give 0.77 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 44.1。
EXAMPLE 37 { [2, 6-dimethoxy-3, 5-bis (2-methoxyphenyl) -2' -biphenyl-di-tert-butylphosphine)](Acetaminophenyl-2-. Eta.) 2 -C, N) Palladium (II) p-toluenesulfonate }
Under inert gas atmosphere, a dry 50 mL Schlenk bottle was charged with (571 mg, 1.0 mmol) and (acetamidophenyl-2-. Eta.) ( 2 -C, N) Palladium (II) p-toluenesulfonate dimer (410 mg, 0.5 mmol), 10 mL of tetrahydrofuran was added via a syringe, the reaction was stirred for 6 hours, the solvent was removed, and column chromatography gave 0.98 g of a yellow solid in 99% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 48.3。
EXAMPLE 38 bis [2',6' -diisopropyl-4 ' - (2-methoxyphenyl) -2-biphenyl-3, 6-dimethoxy-diamantaylphosphine ] cyclooctadienedipalladium (II) }
Add phosphine ligand (705 mg, 1.0 mmol) and [ (COD) Pd (CH) to a dry 50 mL Schlenk flask under inert atmosphere 2 TMS) 2 ](403 mg, 1.0 mmol), 20 mL of n-pentane was added via syringe, the reaction stirred for 48 h, and filtered to give 0.67 g of a black solid in 38% yield.
HR-MS m/z (%): Calcd for C 104 H 141 O 6 P 2 Pd 2 [M + + H] 1759.8273; Found 1759.8266 (100)。
Example 39 2',6' -diisopropoxy-4 '- (2-methylphenyl) -2-biphenyl-3, 4,5, 6-tetramethyl-dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (613.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert gas atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirring and reacting for 6 h, concentrating under reduced pressure to remove the solvent, and purifying the residue by silica gel column chromatography (eluting with dichloromethane) to obtain yellow solid 0.99 g, and the yield is 99%.
31 P NMR (162 MHz, CDCl 3 ) δ: 47.6。
Example 40 {2, 6-bis [2, 6-diisopropyl-4- (2-methoxyphenyl) phenyl ]]Phenyl } -dicyclohexylphosphine (2' -methylaminobiphenyl-2-yl-. Eta.) - 2 -C, N) Palladium Methylbenzenesulfonate (II)
Add phosphine ligand (807.0 mg, 1.0 mmol) and palladium [ (2' -methylaminobiphenyl-2-yl-C, N) methanesulfonate to a dry 50 mL Schlenk flask under inert gas atmosphere] 2 (383.0 mg, 0.5 mmol) and 5 mL of dichloromethane, stirred for 6 h, concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography on silica gel (eluting with dichloromethane) to give 1.02 g of a yellow solid in 86% yield.
31 P NMR (162 MHz, CDCl 3 ) δ: 59.2。
Examples 41 to 46:
[a] in a glove box, 1.2 mmol of 3-bromothiophene, 1.0 mmol of 3-amino-1-methylpyrazole, 1.3 mmol of potassium carbonate, the appropriate amount of catalyst and ligand, 0.13 mL of dodecane (internal standard for GC analysis) and 2 mL of anhydrous THF were placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 110 ℃. The organic phase was analyzed by GC.
Examples 47 to 52:
[a] in a glove box, 2.0 mmol of 4-methylthiophenylboronic acid, 1.0 mmol of 3-bromopyrazole, 2.0 mmol of potassium phosphate, the appropriate amounts of catalyst and ligand, 0.13 mL of dodecane (internal standard for GC analysis), 4 mL of LDioxane and 1mL of H 2 O is placed in a pressure resistant tube. The tube was sealed and suspended in an oil bath at 100 ℃. The organic phase was analyzed by GC.
[b] M. Alexander Düfert, Kelvin L. Billingsley, and Stephen L. Buchwald, J Am Chem Soc. 2013, 135, 12877−12885.
Example 53. Table 3: fluorocarbon coupling reaction [a]
[a] In a glove box, 1.0 mmol of 3-bromo-5-cyanopyridine, 2.0 mmol of silver fluoride, 0.5 mmol of potassium fluoride with the appropriate amount of catalyst, 0.13 mL of dodecane (internal standard for GC analysis) and 2 mL of anhydrous 2-methyltetrahydrofuran were placed in a pressure resistant tube and the organic phase was analyzed by GC.
[b] S. L. Buchwald, et al., Acc. Chem. Res.，2016, 49, 2146-2157。
[c] 
。
Claims (8)
1. The present invention provides phosphine ligands having the general formula I,
wherein R is 1 、R 2 、R 3 And R 4 Each independently selected from H, (C1-C10) alkyl, (C6-C20) aryl, [ O (C1-C10)]Alkoxy and [ N (C1-C10) 2 ]A dialkylamino group;
R 5 and R 6 Each independently selected from (C1-C10) alkyl, [ O (C1-C10)]Alkoxy, [ O (C6-C10)]Aryloxy and [ N (C1-C10) 2 ]A dialkylamino group; r 7 And R 8 Each independently selected from(C1-C20) alkyl, (C3-C10) cycloalkyl, (5-11 membered) heterocycloalkyl, (C6-C20) aryl, (C4-C20) heteroaryl, (C7-C20) arylmethyl, and (C9-C35) 2-linked (hetero) aryl, where (C3-C10) cycloalkyl, (5-11 membered) heterocycloalkyl, (C6-C20) aryl, (C4-C20) heteroaryl, (C7-C20) arylmethylene, and (C9-C35) 2-linked (hetero) aryl may have 1 to 3 heteroatoms independently selected from F, (C1-C10) alkyl which may have heteroatoms, (C5-C10) cycloalkyl which may have heteroatoms, and (C6-C20) aryl, where heteroaryl and 2-linked (hetero) aryl are selected from O, N, and S atoms, and the heteroatoms on the substituents are F, O, S, N, and Si; ar is selected from the group consisting of phenyl, naphthyl and anthracenyl which may have substituents selected from the group consisting of (C1-C10) alkyl, (C3-C10) cycloalkyl, (C6-C20) aryl, [ O (C1-C10)]Alkoxy group of [ O (C6-C10) ]]Aryloxy group of [ N (C1-C10) ] 2 ]And (C6-20) an aryl group.
2. Ar according to claim 1 may be further selected from the group consisting of phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2, 6-dimethylphenyl, 3, 5-dimethylphenyl, 2,4, 6-trimethylphenyl, 2,3,4,5, 6-pentamethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2, 6-diethylphenyl, 3, 5-diethylphenyl, 2,4, 6-triethylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 2, 6-diisopropylphenyl, 3, 5-diisopropylphenyl, 2,4, 6-triisopropylphenyl, 2-sec-butylphenyl, 4-sec-butylphenyl, 2, 6-di-sec-butylphenyl, 2,4, 6-tri-sec-butylphenyl, 2-methoxyphenyl, 2 3-methoxyphenyl, 4-butoxyphenyl, 2, 6-dimethoxyphenyl, 3, 5-dimethoxyphenyl, 2,4, 6-trimethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 2, 6-diphenoxyphenyl, 2,4, 6-triphenoxyphenyl, 2-isopropoxyphenyl, 3-isopropoxyphenyl, 4-isopropoxyphenyl, 2, 6-diisopropoxyphenyl, 2,4, 6-triisopropoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 2, 6-difluorophenyl, 3, 5-difluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 2, 6-bistrifluoromethylphenyl, 2,3,4,5, 6-pentafluorophenyl, 3, 5-bistrifluoromethylphenyl, 2, 5-bistrifluoromethylphenyl, 2-dimethylaminophenyl group, 3-dimethylaminophenyl group, 1-naphthyl group, 2-methoxy-1-naphthyl group, 2-phenoxy-1-naphthyl group, 2-isopropoxy-1-naphthyl group, 9-anthryl group, 10-methoxy-9-anthryl group, 10-nitro-9-anthryl group, 10-nitrile-9-anthryl group and 10-dimethylamino-9-anthryl group.
3. According to the above claims, R 5 And R 6 Each of which may be independently selected from methyl, ethyl, isopropyl, sec-butyl, methoxy, ethoxy, isopropoxy, phenoxy, and dimethylamino.
4. According to the above claims, R 7 And R 8 May further each independently be selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, adamantyl, phenyl, 2-methylphenyl, 2-isopropylphenyl, 2-methoxyphenyl, 2- (dimethylamino) phenyl, 4-methylphenyl, 4-fluorophenyl, 4-methoxyphenyl, 4- (dimethylamino) phenyl, 3, 5-dimethylphenyl, 3, 5-bis (trifluoromethyl) phenyl, 3, 5-difluorophenyl, 3, 5-di-tert-butylphenyl, 2, 6-dimethylphenyl, 2, 6-dimethoxyphenyl, 2, 6-diisopropylphenyl, 2,4, 6-trimethoxyphenyl, 2-biphenyl, 2',6' -dimethyl-2-biphenyl, 2',6' -dimethoxy-2-biphenyl, 2',6' -diisopropoxy-2-biphenyl, 2',6' -bisdimethylamino-2-biphenyl, 2',6' -diisopropyl-2-biphenyl, 2',4',6' -triisopropyl-2-biphenyl, 2-furyl, 2-thienyl, 2-benzofuryl, 2-benzothienyl, 2-pyridyl, 2-tetrahydrofuryl, 3-phenyl-2-furyl, 3-phenyl-2-thienyl, 3- (2, 6-dimethylphenyl) -2-furyl, 3- (2, 6-dimethylphenyl) -2-thienyl, 2' -diisopropoxy-2-biphenyl, 2',6' -bis-dimethylamino-2-biphenyl, 2' -thienyl, 3- (2, 6-dimethoxyphenyl) -2-furyl, 3- (2, 6-dimethoxyphenyl) -2-thienyl, 3- (2, 4, 6-triisopropylphenyl) -2-furyl and 3- (2, 4, 6-triisopropylphenyl) -2-thienyl.
5. The present invention provides a process for the preparation of phosphine ligands as defined in the preceding claims;
the compounds of the general formulae III and IV are reacted in the presence of bases or metals to form compounds of the general formula II,
wherein: x 1 Br, I, li, mgCl, mgBr or MgI;
X 2 、X 3 and X 4 Each independently selected from H, F, cl, br or I;
R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and Ar is as defined above;
when X is 1 Br or I, II first butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium, ethyl lithium, propyl lithium, isopropyl magnesium bromide, isopropyl magnesium chloride, diisopropyl magnesium, magnesium metal or lithium metal is reacted so that X is 1 Conversion to Li, mgCl, mgBr or MgI;
for compounds having the structure of formula III, when X 4 In the case of Cl, br or I, IV is reacted with butyllithium, sec-butyllithium, tert-butyllithium, methyllithium, ethyllithium, propyllithium, isopropyllithium, isopropylmagnesium bromide, isopropylmagnesium chloride, diisopropylmagnesium, magnesium metal or lithium metal, so that X 4 Conversion to Li, mgCl, mgBr or MgI;
when X is 4 Is H and R 5 And R 6 When both are alkoxy or phenoxy, IV is reacted with butyllithium, sec-butyllithium, tert-butyllithium, methyllithium or ethyllithium to give X 4 Lithiated to Li;
using known techniques, X in the general formula III 2 And X 3 Eliminating the formation of corresponding alkynides, reacting with a lithium or magnesium compound of IV, and adding Br 2 Or I 2 To obtain bromide or iodide of II;
when X in II 1 Li, mgCl, mgBr or MgI, with PCl 3 、R 7 PCl 2 、R 8 PCl 2 Or R 7 R 8 PCl reaction, where LiCl, liBr, cuCl, cuBr, cuI, pd (PPh) may or may not be added 3 ) 4 Or PdCl 2 (PPh 3 ) 2 And then the step-by-step addition of R is selected according to the different types of the added phosphorus chloride reagent 7 M and/or R 8 The type and quantity of M, wherein M is Li, na, mgCl, mgBr, mgI, cuCl, cuBr or CuI.
6. The present invention provides the use of a system formed by combining a phosphine ligand as defined in the preceding claims and a transition metal salt or complex of subgroup VIII of the periodic table of the elements as a catalyst;
the phosphine ligand is usually added into a reaction system containing a suitable transition metal precursor compound in situ, or the phosphine ligand and a transition metal salt or a coordination complex are stirred to react to form a catalytic system and then are directly added into the reaction system without separation and purification;
the transition metal here is preferably palladium, nickel, platinum, rhodium, cobalt, iridium and ruthenium, more preferably palladium or nickel.
7. The present invention also provides a palladium complex coordinated by a phosphine ligand as defined in the preceding claims, having the structure of formulae V, VI, VII, VIII, IX, X and XI:
wherein the content of the first and second substances,
l is a phosphine ligand as defined in claims 1 to 5;
X 5 、X 6 、X 7 、X 8 、X 9 and X 10 Is Cl - 、Br - 、I - Mesylate, triflate, benzenesulfonate, p-toluenesulfonate, formate, acetate, trifluoroacetate or benzoate;
R 9 、R 10 、R 11 、R 12 、R 13 and R 14 Each independently selected from H, methyl or phenyl.
8. Use according to claim 6, characterized in that the phosphine ligands are used in catalysis of coupling reactions in which (pseudo) halogenated arene-biaryls form new C-C, C-N, C-O and C-F bonds as substrates.
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