CN112552342A - Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof - Google Patents
Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof Download PDFInfo
- Publication number
- CN112552342A CN112552342A CN202011419127.9A CN202011419127A CN112552342A CN 112552342 A CN112552342 A CN 112552342A CN 202011419127 A CN202011419127 A CN 202011419127A CN 112552342 A CN112552342 A CN 112552342A
- Authority
- CN
- China
- Prior art keywords
- compound
- cdcl
- nmr
- phosphine oxide
- difluoroalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 19
- -1 diaryl phosphine oxide compounds Chemical class 0.000 claims abstract description 11
- HGWXXIZVRRTDKT-UHFFFAOYSA-N ethyl 2,2-difluoro-2-iodoacetate Chemical compound CCOC(=O)C(F)(F)I HGWXXIZVRRTDKT-UHFFFAOYSA-N 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 10
- 239000003446 ligand Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 5
- 101150003085 Pdcl gene Proteins 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 claims description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical group [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010276 construction Methods 0.000 abstract description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 200
- 238000004679 31P NMR spectroscopy Methods 0.000 description 26
- 238000004293 19F NMR spectroscopy Methods 0.000 description 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- 239000007858 starting material Substances 0.000 description 23
- 229910052723 transition metal Inorganic materials 0.000 description 5
- 150000003624 transition metals Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 150000001345 alkine derivatives Chemical group 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- IZGDXVLRMHXOJV-SFHVURJKSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1CCP(O)(=O)C[C@@H](O)CC(O)=O IZGDXVLRMHXOJV-SFHVURJKSA-N 0.000 description 1
- RTTUBUXMNUJHRR-DXRVJIQQSA-N (3s)-4-[[(e)-2-[1-(4-fluorophenyl)-3-propan-2-ylindol-2-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2C(C(C)C)=C(\C=C\P(O)(=O)C[C@@H](O)CC(O)=O)N1C1=CC=C(F)C=C1 RTTUBUXMNUJHRR-DXRVJIQQSA-N 0.000 description 1
- AOSODOHQJJPEAM-VUVZNRFTSA-N (3s)-4-[[(e)-2-[3'-(4-fluorophenyl)spiro[cyclopentane-1,1'-indene]-2'-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)\C=C\C1=C(C=2C=CC(F)=CC=2)C2=CC=CC=C2C11CCCC1 AOSODOHQJJPEAM-VUVZNRFTSA-N 0.000 description 1
- WHQUHTXULUACFD-KRWDZBQOSA-N (3s)-4-[[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]methoxy-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1COP(O)(=O)C[C@@H](O)CC(O)=O WHQUHTXULUACFD-KRWDZBQOSA-N 0.000 description 1
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- BOOYHBPHFVNWNH-OAHLLOKOSA-N 1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C[C@H](C1=CC=C(C=C1)Cl)NC2=NC3=C(C=NN3C(C)(C)C)C(=O)N2CC4=CC=C(C=C4)F BOOYHBPHFVNWNH-OAHLLOKOSA-N 0.000 description 1
- PSWDQTMAUUQILQ-UHFFFAOYSA-N 2-[(6-methoxy-4-methylquinazolin-2-yl)amino]-5,6-dimethyl-1h-pyrimidin-4-one Chemical compound N1=C(C)C2=CC(OC)=CC=C2N=C1NC1=NC(=O)C(C)=C(C)N1 PSWDQTMAUUQILQ-UHFFFAOYSA-N 0.000 description 1
- JWHYSEDOYMYMNM-QGZVFWFLSA-N 2-[4-[(2r)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]sulfanyl-2-methylphenoxy]acetic acid Chemical compound C([C@@H](OCC)CSC=1C=C(C)C(OCC(O)=O)=CC=1)OC1=CC=C(C(F)(F)F)C=C1 JWHYSEDOYMYMNM-QGZVFWFLSA-N 0.000 description 1
- HZYLVYNCWLAIGF-UHFFFAOYSA-N 4-[[[2-(cyclohexylamino)-2-oxoethyl]-(4-propan-2-ylbenzoyl)amino]methyl]-N-hydroxybenzamide Chemical compound CC(C)c1ccc(cc1)C(=O)N(CC(=O)NC1CCCCC1)Cc1ccc(cc1)C(=O)NO HZYLVYNCWLAIGF-UHFFFAOYSA-N 0.000 description 1
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- VCUKKMIXURRDKL-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-ethylphenyl)pyrido[1,2]thieno[3,4-d]pyrimidin-4-one Chemical compound C1=CC(CC)=CC=C1N1C(=O)C(SC=2C3=C(N(C)C)C=CN=2)=C3N=C1 VCUKKMIXURRDKL-UHFFFAOYSA-N 0.000 description 1
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 1
- 229910020257 Cl2F2 Inorganic materials 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- HFIVLLBFACNAFN-UHFFFAOYSA-N [1-amino-2-[2-(4-methoxyphenyl)ethylamino]ethyl]phosphonic acid Chemical compound COc1ccc(CCNCC(N)P(O)(O)=O)cc1 HFIVLLBFACNAFN-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- YBFBENHWPRGUMU-UHFFFAOYSA-N chembl398496 Chemical compound OC(=O)C1=CC=CC=C1NC(=O)N1CCN(C=2N=C3C=CC(O)=CC3=NC=2)CC1 YBFBENHWPRGUMU-UHFFFAOYSA-N 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 229940125796 compound 3d Drugs 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 238000005954 phosphonylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
- C07F9/655354—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl and a preparation method thereof, wherein the structural general formula of the tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl is as follows:
Description
Technical Field
The invention belongs to the technical field of organic phosphine compounds, and particularly relates to a tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl and a preparation method thereof.
Background
The alkenyl phosphine oxide compound has wide application in a plurality of fields of synthetic chemistry, material chemistry, pharmaceutical chemistry, ligand chemistry and the like. The alkenyl phosphine oxide compounds are not only important components of many bioactive molecules and phosphorus-containing materials, but also are useful precursors for synthesis of many phosphorus ligands. The tetra-substituted alkenyl phosphine oxide compound has great application potential in the aspects of drug molecule development, molecular devices and liquid crystal materials due to unique structure, physical property and photoelectric property. On the other hand, fluorine atoms have small atomic radius and strong electronegativity, and the original physicochemical property and biological property can be remarkably adjusted by doping the fluorine atoms into organic molecules. As bioisosteres of oxygen atoms or carbonyl groups, difluoromethylene (CF)2) Has important application in the fields of medicine and material. Therefore, it is of great significance to develop a versatile synthesis method for introducing a difluoroalkyl group into a tetra-substituted alkenylphosphine oxide molecule.
At present, the synthesis method of the alkenyl phosphine oxide compound mainly comprises the following steps: 1) transition metal catalyzed addition of P (O) H compounds to terminal alkynes; 2) transition metal catalyzed oxidative coupling of P (O) H compounds to terminal olefins; 3) transition metal catalyzed coupling of P (O) H compounds with alkenyl halides; 4) transition metal catalyzed decarboxylation coupling of p (o) H compounds with cinnamic acid derivatives; 5) the transition metal catalyzes the decarboxylative addition of the P (O) H compound to the arylacetylenic acid. However, these synthetic methods are not basically suitable for the synthesis of tetra-substituted alkenylphosphine oxides. In addition, the synthesis of trisubstituted difluoroalkylated alkenylphosphine oxides by palladium-catalyzed difluoroalkylation-phosphonylation of terminal alkynes has also been reported. However, the synthesis method of the tetra-substituted alkenylphosphine oxide compound containing a difluoroalkyl group is still very deficient.
Disclosure of Invention
The invention solves the technical problem of providing a tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl and having a novel structure and a preparation method thereof.
The invention adopts the following technical scheme for solving the technical problems, and the tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl is characterized in that the structural general formula of the tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl is as follows:
wherein R is1Is H, methyl, fluorine or chlorine; r2Is H, methyl, ethyl, tert-butyl, phenyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, acetyl or cyano; r3Is H, methyl, methoxy, chlorine or phenyl; x is O, S or NTs.
The invention relates to a preparation method of a tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl, which is characterized by comprising the following specific steps: adding 1, 6-eneyne compounds 1, ethyl difluoroiodoacetate, diaryl phosphine oxide compounds 2, a catalyst, a ligand and alkali into a solvent, stirring and reacting completely at 60-90 ℃ in an inert gas atmosphere, and performing post-treatment to obtain target products, namely, tetra-substituted alkenyl phosphine oxide compounds 3 containing difluoroalkyl, wherein the reaction equation in the preparation process is as follows:
wherein R is1Is H, methyl, fluorine or chlorine; r2Is H, methyl, ethyl, tert-butyl, phenyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, acetyl or cyano; r3Is H, methyl, methoxy, chlorine or phenyl; x is O, S or NTs;
the catalyst is trans-bis (triphenylphosphine) dichloridePalladium (PdCl) base2(PPh3)2) Palladium chloride (PdCl)2) Palladium trifluoroacetate (Pd (TFA))2) Bis (dibenzylideneacetone) palladium (Pd)2(dba)3) Palladium acetate (Pd (OAc)2) Or tetratriphenylphosphine palladium (Pd (PPh)3)4)；
The ligand is triphenylphosphine (PPh)3) 1,1' -bisdiphenylphosphinoferrocene (dppf) or 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene (xanthphos);
the alkali is potassium carbonate, potassium phosphate, sodium carbonate or cesium carbonate;
the solvent is 1, 4-dioxane, toluene, tetrahydrofuran or 1, 2-Dichloroethane (DCE).
Preferably, the amount of the catalyst is 5 to 10% equiv, preferably 10% equiv; the dosage of the ligand is 10-20% equiv, preferably 20% equiv; the dosage of the alkali is 1-3 equiv, preferably 2 equiv; the dosage of the difluoro iodoacetic acid ethyl ester is 1-3 equiv, preferably 2.0 equiv; the dosage of the diaryl phosphine oxide compound is 1-4 equiv, and preferably 3.2 equiv.
Preferably, the reaction temperature in the preparation process is 80 ℃, and the reaction time is 10-24 h, preferably 24 h.
Preferably, the inert gas atmosphere is argon or nitrogen.
Preferably, the post-treatment comprises the following specific processes: extracting the reaction liquid after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, performing column separation after spin-drying, wherein a column-passing solvent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 3: 1.
The invention has the following beneficial effects: the invention provides a method for synthesizing tetra-substituted alkenyl phosphine oxide containing fluoroalkyl by taking 1, 6-eneyne compounds, difluoroiodoacetic acid ethyl ester and diaryl phosphine oxide compounds as raw materials with high efficiency and high selectivity; the preparation method has mild conditions, is simple and easy to operate, has good substrate applicability, and realizes the introduction of difluoroalkyl and the construction of tetra-substituted alkenyl phosphine by a one-pot method; the tetra-substituted alkenyl phosphine oxide containing difluoroalkyl prepared by the invention has stronger innovation in structure.
Detailed Description
The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.
Example 1
PdCl was added to a 10mL Schlenk flask in sequence2(PPh3)2(14.1mg，0.02mmol)，Xantphos(23.2mg，0.04mmol)，K2CO3(55.2mg, 0.4mmol), diphenylphosphine oxide 2a (129.3mg, 0.64mmol) and 1, 2-dichloroethane solvent (2mL) were added, followed by 1, 6-enyne compound 1a (44.0mg, 0.2mmol), ethyl difluoroiodoacetate (100.0mg, 0.4mmol), plugging with a stopper, rapidly purging argon three times with a double-row tube, reacting at 80 ℃ for 22h, extracting with 2x8mL ethyl acetate, combining the organic phases, drying over anhydrous sodium sulfate, filtering, spin-drying, passing through a column with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 3:1 to obtain the target compound (compound 3a)68.5mg, yield 63%.1H NMR(400MHz,CDCl3)δ7.59–7.46(m,6H),7.39–7.34(m,4H),7.26–7.22(m,2H),7.21–7.15(m,1H),7.12–7.08(m,1H),6.94–6.91(m,1H),6.80(d,J＝8.1Hz,1H),6.58–6.54(m,2H),6.52–6.48(m,1H),5.79(d,J＝8.0Hz,1H),4.39–4.25(m,2H),3.47–3.35(m,1H),2.78–2.63(m,1H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝32.2Hz),163.0,154.8(d,J＝8.1Hz),136.4(d,J＝9.4Hz),132.7(d,J＝10.1Hz),132.5,132.4(d,J＝9.6Hz),132.2(d,J＝2.7Hz),132.0(d,J＝2.6Hz),131.7(d,J＝104.7Hz),131.4(d,J＝104.9Hz),131.1(d,J＝3.9Hz),130.1(d,J＝3.8Hz),129.3–129.1(m),128.4(d,J＝9.1Hz),128.3(d,J＝9.2Hz),128.1(d,J＝2.1Hz),126.3,124.6(d,J＝94.7Hz),124.4(d,J＝14.5Hz),121.0,115.2(dd,J＝252.9,248.8Hz),111.4,79.7–79.6(m),62.9,41.5(t,J＝24.1Hz),14.1.31P NMR(243MHz,CDCl3)δ28.18(s).19F NMR(565MHz,CDCl3)δ-100.95(d,J＝264.3Hz,1F),-107.93(d,J＝265.5Hz,1F).HRMS:[M+H]+m/z calcd for C32H28F2O4P+:545.1688,found:545.1677。
Example 2
With Pd (PPh)3)4(23.1mg, 0.02mmol) in place of PdCl2(PPh3)2Otherwise, the same procedure as in example 1 was repeated, whereby the yield of the objective compound 3a was 53%.
Example 3
The desired product 3a was obtained in 46% yield from example 1, substituting dppf (22.2mg, 0.04mmol) for Xantphos.
Example 4
With Na2CO3(42.4mg, 0.4mmol) in place of K2CO3Otherwise, the same procedure as in example 1 was repeated, whereby the yield of the objective compound 3a was 44%.
Example 5
The same procedure as in example 1 was repeated except for using 1, 4-dioxane (2mL) in place of DCE to obtain the desired product 3a in 21% yield.
Example 6
The same procedures used in example 1 were repeated except for using 1, 6-enyne compound 1b (44.0mg, 0.2mmol) as a starting material to give 69.2mg of the objective compound (compound 3b) in a yield of 62%.1H NMR(400MHz,CDCl3)δ7.59–7.46(m,6H),7.40–7.33(m,4H),7.20–7.15(m,1H),7.03(d,J＝7.7Hz,1H),6.91(d,J＝7.7Hz,1H),6.81–6.78(m,2H),6.62–6.58(m,1H),6.52(t,J＝7.4Hz,1H),6.43–6.39(m,1H),5.84(d,J＝8.0Hz,1H),4.39–4.25(m,2H),3.45–3.33(m,1H),2.77–2.63(m,1H),2.31(s,3H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝31.9Hz),162.9,154.8(d,J＝8.0Hz),137.9(d,J＝2.4Hz),133.0(d,J＝9.5Hz),132.6,132.6(d,J＝9.4Hz),132.5(d,J＝9.6Hz),132.1(d,J＝2.4Hz),131.9(d,J＝2.8Hz),131.7(d,J＝103.6Hz),131.1(d,J＝3.9Hz),130.4(d,J＝103.5Hz),130.0–129.8(m),128.4(d,J＝6.0Hz),128.3(d,J＝5.6Hz),126.3,124.6(d,J＝95.0Hz),124.5(d,J＝14.6Hz),121.0,115.2(dd,J＝252.9,248.8Hz),111.3,79.7–79.5(m),62.9,41.6(t,J＝24.4Hz),21.4,14.1.31P NMR(243MHz,CDCl3)δ28.45.19F NMR(565MHz,CDCl3)δ-100.97(d,J＝264.1Hz,1F),-107.93(d,J＝265.2Hz,1F).HRMS:[M+H]+m/z calcd for C33H30F2O4P+:559.1844,found:559.1845。
Example 7
The same procedures used in example 1 were repeated except for using 1, 6-enyne compound 1c (46.8mg, 0.2mmol) as a starting material to give 69.2mg of the objective compound (compound 3c) in a yield of 62%. H NMR (400MHz, CDCl)3)δ7.64–7.45(m,6H),7.41–7.33(m,4H),7.20–6.98(m,3H),6.81–6.49(m,4H),6.42–6.24(m,1H),5.87–5.85(m,1H),4.40–4.24(m,2H),3.50–3.29(m,1H),2.77–2.62(m,1H),2.31(s,1.5H),2.02(s,1.5H),1.32–1.28(m,3H).13C NMR(100MHz,CDCl3)δ164.4(t,J＝32.2Hz),164.3(t,J＝32.2Hz),163.0,162.9,138.9(d,J＝6.9Hz),136.1(d,J＝9.4Hz),132.7(d,J＝9.7Hz),132.6(d,J＝9.6Hz),132.5,132.4(d,J＝9.4Hz),132.1(d,J＝2.6Hz),132.04(d,J＝3.0Hz),132.0(d,J＝2.4Hz),131.9(d,J＝3.4Hz),131.4(d,J＝105.3Hz),131.3(d,J＝109.3Hz),130.9(d,J＝3.7Hz),129.0,128.9,128.7(d,J＝1.6Hz),128.5(d,J＝12.2Hz),128.4(d,J＝12.1Hz),128.2(d,J＝12.8Hz),128.1(d,J＝11.2Hz),126.9(d,J＝4.1Hz),126.3(d,J＝8.0Hz),125.0(d,J＝94.6Hz),124.7(d,J＝93.3Hz),124.5(d,J＝14.7Hz),124.4(d,J＝14.2Hz),121.0(d,J＝3.7Hz),115.2(dd,J＝252.9,248.8Hz),115.1(dd,J＝252.9,248.8Hz),111.4,111.3,79.7–79.6(m),79.6–79.5(m),62.9,41.6(t,J＝24.0Hz),41.5(t,J＝24.3Hz),21.4,21.3,14.1.31P NMR(243MHz,CDCl3)δ28.30.19F NMR(471MHz,CDCl3)δ(-100.96(d,J＝264.8Hz),-107.76(d,J＝265.0Hz),1F),(-101.02(d,J＝265.0Hz),-107.90(d,J＝264.8Hz),1F).HRMS:[M+H]+m/z calcd for C33H30F2O4P+:559.1844,found:559.1832。
Example 8
Using 1, 6-eneyne compound 1d (46.8mg, 0.2mmol) as a starting material and the same conditions as in example 1, 53.6mg of the objective compound (compound 3d) was obtained in 48% yield.1H NMR(400MHz,CDCl3)δ7.82(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.69(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.58–7.53(m,4H),7.52–7.47(m,2H),7.39–7.36(m,4H),7.21–7.18(m,1H),7.08–7.06(m,1H),6.81(d,J＝8.2Hz,1H),6.70–6.68(m,1H),6.55–6.48(m,1H),6.50(t,J＝7.5Hz,1H),5.78(d,J＝8.0Hz,1H),4.37–4.27(m,2H),3.43–3.36(m,1H),2.76–2.66(m,1H),2.57(s,3H),1.30(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ197.7,164.2(t,J＝32.3Hz),163.2,155.1(d,J＝6.8Hz),141.8(d,J＝9.3Hz),136.4(d,J＝1.6Hz),133.1,132.5(d,J＝9.9Hz),132.4(d,J＝9.9Hz),132.3(d,J＝2.1Hz),131.6(d,J＝3.8Hz),131.4(d,J＝105.3Hz),131.0(d,J＝105.4Hz),130.5(d,J＝3.6Hz),129.0(d,J＝16.6Hz),128.6(d,J＝12.2Hz),128.5(d,J＝12.0Hz),126.0,123.9(d,J＝13.5Hz),123.7(d,J＝94.1Hz),121.2,115.2(dd,J＝254.7,254.8Hz),111.7,79.8–79.7(m),63.0,41.4(t,J＝23.2Hz),26.8,14.1.31P NMR(243MHz,CDCl3)δ28.06.19F NMR(565MHz,CDCl3)δ-101.01(d,J＝265.8Hz,1F),-107.71(d,J＝264.9Hz,1F).HRMS:[M+Na]+m/z calcd for C34H29F2NaO5P+:609.1613,found:609.1616。
Example 9
Using 1, 6-enyne compound 1e (49.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 51.3mg of the objective compound (compound 3e) was obtained with a yield of 61%.1H NMR(400MHz,CDCl3)δ7.59–7.45(m,6H),7.39–7.32(m,4H),7.20–7.15(m,1H),7.04(d,J＝7.8Hz,1H),6.92(d,J＝7.7Hz,1H),6.82–6.78(m,2H),6.59–6.56(m,1H),6.51(t,J＝7.4Hz,1H),6.46–6.43(m,1H),5.86(d,J＝8.0Hz,1H),4.39–4.24(m,2H),3.46–3.35(m,1H),2.78–2.65(m,1H),2.60(q,J＝7.5Hz,2H),1.30(t,J＝7.2Hz,3H),1.19(t,J＝7.5Hz,3H).13C NMR(100MHz,CDCl3)δ164.5(t,J＝32.6Hz),162.9,154.6(d,J＝7.9Hz),144.4(d,J＝2.3Hz),133.3(d,J＝9.5Hz),132.6,132.6(d,J＝9.4Hz),132.1(d,J＝2.6Hz),131.8(d,J＝104.8Hz),131.9(d,J＝3.5Hz),131.5(d,J＝104.8Hz),131.0(d,J＝4.0Hz),129.9(d,J＝4.0Hz),128.7–128.5(m),128.4(d,J＝7.3Hz),128.2(d,J＝7.2Hz),126.3,124.6(d,J＝96.0Hz),124.5(d,J＝14.4Hz),121.0,115.1(dd,J＝254.7,254.8Hz),111.3,79.7–79.5(m),62.9,41.5(t,J＝23.1Hz),28.7,15.9,14.1.31P NMR(243MHz,CDCl3)δ28.86.19F NMR(565MHz,CDCl3)δ-100.96(d,J＝266.0Hz,1F),-103.69(d,J＝265.5Hz,1F).HRMS:[M+H]+m/z calcd for C34H32F2O4P+:573.2001,found:573.2002。
Example 10
Using 1, 6-enyne compound 1f (55.2mg, 0.2mmol) as a starting material and the same conditions as in example 1, the objective compound (compound 3f) was obtained in 66.0mg, yield 55%.1H NMR(400MHz,CDCl3)δ7.57–7.45(m,6H),7.37–7.31(m,4H),7.23–7.15(m,2H),7.11–7.08(m,1H),6.83–6.78(m,2H),6.57–6.45(m,3H),5.87(d,J＝8.0Hz,1H),4.39–4.25(m,2H),3.46–3.35(m,1H),2.78–2.63(m,1H),1.30(t,J＝7.2Hz,3H),1.27(s,9H).13C NMR(100MHz,CDCl3)δ164.4(t,J＝32.6Hz),163.0,154.6(d,J＝7.9Hz),151.4(d,J＝2.6Hz),133.2(d,J＝9.5Hz),132.6(d,J＝2.7Hz),132.5(d,J＝3.4Hz),132.4,132.0(d,J＝2.8Hz),131.9(d,J＝104.3Hz),131.89(d,J＝2.7Hz),131.5(d,J＝104.4Hz),131.1(d,J＝4.0Hz),129.5(d,J＝3.9Hz),128.4(d,J＝8.7Hz),128.2(d,J＝8.9Hz),126.3,126.1(d,J＝1.2Hz),126.0(d,J＝2.1Hz),124.6(d,J＝95.3Hz),124.5(d,J＝14.5Hz),121.0,115.2(dd,J＝254.7,254.8Hz),111.4,79.7–79.6(m),62.9,41.5(t,J＝23.5Hz),34.7,31.5,27.1,14.1.31P NMR(243MHz,CDCl3)δ28.67.19F NMR(471MHz,CDCl3)δ-100.94(d,J＝265.0Hz,1F),-107.90(d,J＝265.0Hz,1F).HRMS:[M+H]+m/z calcd for C36H36F2O4P+:601.2314,found:601.2311。
Example 11
Using 1g (59.2mg, 0.2mmol) of the 1, 6-enyne compound as a starting material and the same conditions as in example 1, 73.1mg of the objective compound (compound 3g) was obtained with a yield of 59%.1H NMR(400MHz,CDCl3)δ7.64–7.57(m,6H),7.53–7.34(m,11H),7.20(t,J＝7.4Hz,1H),7.02–6.99(m,1H),6.82(d,J＝8.1Hz,1H),6.64–6.60(m,2H),6.53(t,J＝7.5Hz,1H),5.98(d,J＝8.0Hz,1H),4.39–4.28(m,2H),3.49–3.38(m,1H),2.81–2.67(m,1H),1.32(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.6(t,J＝32.3Hz),163.1,140.6(d,J＝2.3Hz),140.1,135.3(d,J＝9.4Hz),132.8,132.6(d,J＝9.8Hz),132.5(d,J＝9.8Hz),132.2(d,J＝2.5Hz),132.1(d,J＝2.5Hz),131.7(d,J＝104.0Hz),131.6(d,J＝4.0Hz),131.4(d,J＝105.1Hz),130.5(d,J＝4.7Hz),129.1,128.5(d,J＝6.7Hz),128.4(d,J＝6.7Hz),127.9,127.7–127.6(m),127.1,126.3,124.3(d,J＝14.3Hz),124.2(d,J＝94.8Hz),121.1,115.2(dd,J＝254.7,254.8Hz),111.5,79.7–79.6(m),62.9,41.5(t,J＝24.0Hz),14.1.31P NMR(243MHz,CDCl3)δ28.35.19F NMR(471MHz,CDCl3)δ-100.97(d,J＝265.0Hz,1F),-107.70(d,J＝265.0Hz,1F).HRMS:[M+Na]+m/z calcd for C38H31F2NaO4P+:643.1820,found:643.1811。
Example 12
Using 1, 6-eneyne compound 1h (47.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 65.2mg of the objective compound (compound 3h) was obtained in 58% yield.1H NMR(400MHz,CDCl3)δ7.59–7.48(m,6H),7.42–7.36(m,4H),7.26–7.18(m,1H),6.97–6.87(m,2H),6.84–6.79(m,2H),6.58–6.50(m,3H),5.83(d,J＝8.0Hz,1H),4.39–4.24(m,2H),3.45–3.34(m,1H),2.78–2.64(m,1H),1.30(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.4(t,J＝32.6Hz),163.1,162.5(dd,J＝248.9,2.5Hz),155.5(d,J＝7.7Hz),133.0(d,J＝4.4Hz),132.9,132.8(d,J＝4.0Hz),132.5(d,J＝9.7Hz),132.4(d,J＝9.5Hz),132.3(d,J＝2.5Hz),132.2(d,J＝2.6Hz),132.1(d,J＝21.3Hz),132.0(d,J＝4.8Hz),131.9(d,J＝4.2Hz),131.5(d,J＝104.1Hz),131.1(d,J＝105.0Hz),128.6(d,J＝5.7Hz),128.4(d,J＝5.7Hz),126.0,124.2(d,J＝14.3Hz),123.4(d,J＝95.4Hz),121.2,116.4(d,J＝11.4Hz),116.2(d,J＝9.6Hz),115.1(dd,J＝254.7,254.8Hz),111.6,79.7–79.6(m),62.9,41.5(t,J＝22.8Hz),14.1.31P NMR(243MHz,CDCl3)δ28.36.19F NMR(565MHz,CDCl3)δ-101.05(d,J＝265.6Hz,1F),-107.73(d,J＝264.8Hz,1F),-113.03(s,1F).HRMS:[M+H]+m/z calcd for C32H27F3O4P+:563.1594,found:563.1592。
Example 13
Using 1, 6-enyne compound 1i (50.8mg, 0.2mmol) as a starting material and the same conditions as in example 1, 65.9mg of the objective compound (compound 3i) was obtained with a yield of 57%.1H NMR(400MHz,CDCl3)δ7.59–7.48(m,6H),7.42–7.36(m,4H),7.26–7.18(m,1H),6.97–6.87(m,2H),6.84–6.79(m,2H),6.58–6.50(m,3H),5.83(d,J＝8.0Hz,1H),4.39–4.24(m,2H),3.45–3.34(m,1H),2.78–2.64(m,1H),1.30(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.4(t,J＝32.6Hz),163.1,162.5(dd,J＝248.9,2.5Hz),155.5(d,J＝7.7Hz),133.0(d,J＝4.4Hz),132.9,132.8(d,J＝4.0Hz),132.5(d,J＝9.7Hz),132.4(d,J＝9.5Hz),132.3(d,J＝2.5Hz),132.2(d,J＝2.6Hz),132.1(d,J＝21.3Hz),132.0(d,J＝4.8Hz),131.9(d,J＝4.2Hz),131.5(d,J＝104.1Hz),131.1(d,J＝105.0Hz),128.6(d,J＝5.7Hz),128.4(d,J＝5.7Hz),126.0,124.2(d,J＝14.3Hz),123.4(d,J＝95.4Hz),121.2,116.4(d,J＝11.4Hz),116.2(d,J＝9.6Hz),115.1(dd,J＝254.7,254.8Hz),111.6,79.7–79.6(m),62.9,41.5(t,J＝22.8Hz),14.1.31P NMR(243MHz,CDCl3)δ28.36.19F NMR(565MHz,CDCl3)δ-101.05(d,J＝265.6Hz,1F),-107.73(d,J＝264.8Hz,1F),-113.03(s,1F).HRMS:[M+H]+m/z calcd for C32H27F3O4P+:563.1594,found:563.1592。
Example 14
Using 1, 6-enyne compound 1j (59.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 46.0mg of the objective compound (compound 3j) was obtained with a yield of 37%.1H NMR(400MHz,CDCl3)δ7.60–7.50(m,6H),7.43–7.36(m,5H),7.26–7.19(m,2H),6.83–6.79(m,2H),6.59–6.55(m,2H),6.45–6.41(m,1H),5.88(d,J＝8.0Hz,1H),4.39–4.25(m,2H),3.44–3.33(m,1H),2.78–2.64(m,1H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.1(t,J＝32.6Hz),163.0,155.1(d,J＝7.4Hz),135.2(d,J＝9.6Hz),132.9,132.8(d,J＝4.8Hz),132.4(d,J＝9.7Hz),132.3(d,J＝11.0Hz),132.2,132.1(d,J＝2.7Hz),131.7(d,J＝3.9Hz),131.2(d,J＝104.6Hz),130.8(d,J＝104.9Hz),128.4(d,J＝4.4Hz),128.3(d,J＝3.9Hz),125.9,123.9(d,J＝14.1Hz),123.1(d,J＝94.7Hz),122.3(d,J＝2.8Hz),121.1,114.9(dd,J＝254.7,254.8Hz),111.5,79.6–79.4(m),62.8,41.3(t,J＝23.2Hz),13.9.31P NMR(243MHz,CDCl3)δ28.00.19F NMR(565MHz,CDCl3)δ-101.09(d,J＝264.3Hz,1F),-107.69(d,J＝265.7Hz,1F).C32H27BrF2O4P+:623.0793,found:623.0795。
Example 15
Using 1, 6-eneyne compound 1k (47.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 55.0mg of the objective compound (compound 3k) was obtained in 49% yield.1H NMR(600MHz,CDCl3)δ7.61–7.49(m,6H),7.44–7.36(m,4H),7.24–7.07(m,2H),6.98–6.94(m,1H),6.82(d,J＝8.2Hz,1H),6.77–6.65(m,1H),6.58–6.52(m,2H),6.40–6.26(m,1H),5.88–5.86(m,1H),4.39–4.25(m,2H),3.46–3.35(m,1H),2.78–2.64(m,1H),1.33–1.29(m,3H).13C NMR(100MHz,CDCl3)δ164.2(t,J＝32.3Hz),163.2,163.1(d,J＝248.6Hz),155.3(d,J＝7.1Hz),138.3(d,J＝8.3Hz),133.1,132.5(d,J＝4.0Hz),132.5(d,J＝2.3Hz),132.4(d,J＝9.9Hz),132.4(d,J＝1.3Hz),132.3(d,J＝2.0Hz),132.2(d,J＝2.9Hz),131.4(d,J＝104.4Hz),131.0(d,J＝105.4Hz),130.9–130.7(m),128.6(d,J＝12.5Hz),128.5(d,J＝12.1Hz),128.4(d,J＝12.1Hz),127.0(t,J＝3.4Hz),126.1(d,J＝6.1Hz),125.9(t,J＝3.6Hz),123.9(d,J＝14.2Hz),123.2(d,J＝94.9Hz),121.2(d,J＝6.5Hz),118.1(dd,J＝21.5,3.9Hz),117.1(dd,J＝21.7,3.6Hz),115.2(dd,J＝8.0,2.2Hz),115.0(dd,J＝254.7,254.8Hz),115.1–114.9(m),111.6,79.7–79.6(m),63.0,41.4(t,J＝24.0Hz),14.1.31P NMR(243MHz,CDCl3)δ31P NMR(243MHz,CDCl3)δ28.45(d,J＝25.2Hz).19F NMR(471MHz,CDCl3)δ-101.10(dd,J＝265.1,6.7Hz,1F),-107.63(dd,J＝265.3,39.2Hz,1F),-111.45(d,J＝65.3Hz,1F).HRMS:[M+H]+m/z calcd for C32H27F3O4P+:563.1594,found:563.1597。
Example 16
Using 1l (50.8mg, 0.2mmol) of the 1, 6-enyne compound as a starting material and the same conditions as in example 1, 49.7mg of the objective compound (compound 3l) was obtained with a yield of 43%.1H NMR(600MHz,CDCl3)δ7.63–7.49(m,6H),7.44–7.38(m,4H),7.25–7.04(m,3H),6.90–6.82(m,2H),6.59–6.50(m,3H),5.88(d,J＝7.8Hz,1H),4.38–4.27(m,2H),3.43–3.34(m,1H),2.79–2.63(m,1H)1.30(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl3)δ164.2(t,J＝32.3Hz),163.2(d,J＝2.4Hz),155.3(dd,J＝7.4,2.4Hz),138.3(dd,J＝9.6,2.2Hz),134.9(d,J＝1.8Hz),133.1(d,J＝1.4Hz),132.5(d,J＝5.1Hz),132.5(d,J＝7.5Hz),132.4(d,J＝5.1Hz),132.4(d,J＝9.5Hz),132.2(d,J＝2.9Hz),131.5(d,J＝104.7Hz),131.4(d,J＝104.9Hz),131.2(d,J＝3.6Hz),131.1(d,J＝104.9Hz),130.8(d,J＝105.2Hz),130.5(d,J＝1.4Hz),130.3(d,J＝2.7Hz),129.3(d,J＝3.8Hz),128.6(d,J＝1.2Hz),128.5(d,J＝5.9Hz),128.5,128.4(d,J＝3.4Hz),128.3–128.2(m),126.1(d,J＝8.0Hz),123.9(dd,J＝14.2,4.7Hz),123.2(dd,J＝94.8,9.0Hz),121.3(d,J＝3.8Hz),115.0(dd,J＝254.7,254.8Hz),111.6,79.7–79.6(m),63.0,41.4(t,J＝24.2Hz),14.1.31P NMR(243MHz,CDCl3)δ28.39(d,J＝8.6Hz).19F NMR(471MHz,CDCl3)δ-101.12(dd,J＝265.2,13.3Hz,1F),-107.60(dd,J＝265.2,75.9Hz,1F).HRMS:[M+H]+m/z calcd for C32H27ClF2O4P+:579.1298,found:579.1296。
Example 17
Using 1, 6-eneyne compound 1m (50.0mg, 0.2mmol) as a starting material and the same conditions as in example 1, 50.5mg of the objective compound (compound 3m) was obtained in a yield of 43%.1H NMR(400MHz,CDCl3)δ7.59–7.47(m,6H),7.41–7.34(m,4H),7.21–7.16(m,1H),6.83–6.74(m,3H),6.66–6.51(m,3H),6.45–6.41(m,1H),5.88(d,J＝8.0Hz,1H),4.39–4.24(m,2H),3.77(s,3H),3.46–3.32(m,1H),2.77–2.62(m,1H),1.30(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝32.6Hz),163.0,159.4(d,J＝2.9Hz),155.2(d,J＝8.6Hz),132.7,132.6(d,J＝9.5Hz),132.5(d,J＝9.5Hz),132.4(d,J＝3.6Hz),131.7(d,J＝103.9Hz),132.1(d,J＝2.7Hz),132.0(d,J＝2.9Hz),131.4(d,J＝105.8Hz),131.3(d,J＝3.7Hz),128.4(d,J＝3.4Hz),128.3(d,J＝3.5Hz),126.3,124.5(d,J＝14.0Hz),124.1(d,J＝96.2Hz),121.1,115.2(dd,J＝254.7,254.8Hz),114.6–114.5(m),111.4,79.7–79.5(m),62.9,55.4,41.6(t,J＝23.2Hz),14.1.31P NMR(243MHz,CDCl3)δ28.48.19F NMR(565MHz,CDCl3)δ-100.96(d,J＝266.6Hz,1F),-107.83(d,J＝264.8Hz,1F).HRMS:[M+H]+m/z calcd for C33H30F2O5P+:575.1793,found:575.1792。
Example 18
Using 1, 6-eneyne compound 1n (57.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 57.5mg of the objective compound (compound 3n) was obtained in a yield of 47%.1H NMR(400MHz,CDCl3)δ7.59–7.47(m,7H),7.42–7.35(m,5H),7.25–7.19(m,1H),7.08(d,J＝8.1Hz,1H),6.83(d,J＝8.2Hz,1H),6.71(d,J＝8.1Hz,1H),6.58–6.52(m,2H),5.78(d,J＝8.0Hz,1H),4.39–4.25(m,2H),3.47–3.35(m,1H),1.30(t,J＝7.2Hz,3H).3C NMR(100MHz,CDCl3)δ164.2(t,J＝32.6Hz),163.3,155.3(d,J＝6.7Hz),140.6(d,J＝9.3Hz),133.2,132.5(d,J＝8.1Hz),132.4(d,J＝11.7Hz),132.4(d,J＝9.2Hz),131.6(d,J＝3.9Hz),131.3(d,J＝104.8Hz),130.8(d,J＝105.1Hz),130.7(d,J＝3.7Hz),128.7(d,J＝6.7Hz),128.5(d,J＝7.2Hz),126.2–126.0(m),125.9,124.0(q,J＝272.1Hz),123.9(d,J＝14.0Hz),123.3(d,J＝94.3Hz),121.3,115.0(dd,J＝254.7,254.8Hz),111.8,79.8–79.7(m),63.0,41.4(t,J＝25.5Hz),14.1.31P NMR(243MHz,CDCl3)δ28.31.19F NMR(565MHz,CDCl3)δ-62.56(s,3F),-101.11(d,J＝266.0Hz,1F),-107.67(d,J＝265.7Hz,1F).HRMS:[M+H]+m/z calcd for C32H27F5O4P+:613.1562,found:613.1566。
Example 19
Using 1, 6-eneyne compound 1o (55.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, the objective compound (compound 3o) was obtained in 71.0mg, yield 59%.1H NMR(400MHz,CDCl3)δ7.90(dd,J1＝8.2Hz,J2＝1.6Hz,1H),7.78(dd,J1＝8.2Hz,J2＝1.6Hz,1H),7.59–7.46(m,6H),7.40–7.35(m,4H),7.23–7.17(m,1H),7.05–7.02(m,1H),6.81(d,J＝8.2Hz,1H),6.68–6.65(m,1H),6.57–6.53(m,1H),6.49(t,J＝7.3Hz,1H),5.77(d,J＝8.0Hz,1H),4.38–4.23(m,2H),3.90(s,3H),3.46–3.35(m,1H),2.78–2.64(m,1H),1.29(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ166.7,164.2(t,J＝32.6Hz),163.2,154.9(d,J＝6.8Hz),141.5(d,J＝9.4Hz),133.1,132.5(d,J＝9.6Hz),132.4(d,J＝6.6Hz),132.3(d,J＝2.5Hz),131.3(d,J＝104.7Hz),131.3(d,J＝2.8Hz),130.9(d,J＝104.9Hz),130.4–130.2(m),130.3(d,J＝3.8Hz),129.7(d,J＝2.1Hz),128.6(d,J＝8.7Hz),128.5(d,J＝8.7Hz),126.0,123.9(d,J＝14.0Hz),123.8(d,J＝94.5Hz),121.2,115.2(dd,J＝254.7,254.8Hz),111.6,79.7–79.6(m),62.9,52.5,41.4(t,J＝23.2Hz),14.1.31P NMR(243MHz,CDCl3)δ28.03.19F NMR(565MHz,CDCl3)δ-101.05(d,J＝279.0Hz,1F),-107.74(d,J＝264.9Hz,1F).HRMS:[M+H]+m/z calcd for C34H30F2O6P+:603.1743,found:603.1735。
Example 20
The same procedures used in example 1 were repeated except for using 1, 6-enyne compound 1p (101.2mg, 0.2mmol) as a starting material to give 69.7mg of the objective compound (compound 3p) in a yield of 42%.1H NMR(400MHz,CDCl3)δ7.92–7.85(m,1H),7.79–7.72(m,1H),7.60–7.49(m,6H),7.43–7.35(m,4H),7.24–7.19(m,1H),7.11–7.02(m,1H),6.83(d,J＝8.3Hz,1H),6.73–6.64(m,1H),6.58–6.49(m,2H),5.96–5.94(m,1H),5.77(d,J＝7.8Hz,1H),5.47(s,1H),4.66(d,J＝3.7Hz,1H),4.38–4.23(m,4H),4.12–4.04(m,2H),3.46–3.34(m,1H),2.80–2.65(m,1H),1.56(s,3H),1.42(s,3H),1.33(s,3H),1.32–1.28(m,6H).13C NMR(100MHz,CDCl3)δ164.9,164.2(td,J＝32.3,3.7Hz),163.3(d,J＝2.9Hz),155.2(d,J＝6.1Hz),142.2(dd,J＝9.4,2.7Hz),133.7(d,J＝2.8Hz),133.2,132.56,132.51,132.47,132.41,132.38,132.32,131.7–131.6(m),131.5(d,J＝4.9Hz),131.46,131.44(d,J＝104.8Hz),130.7(d,J＝105.4Hz),130.68,130.64,130.61,130.54,130.51,130.48,130.41,130.35,130.3,129.2–129.0(m),128.9,128.7(d,J＝6.7Hz),128.6(d,J＝1.8Hz),128.6(d,J＝2.8Hz),128.5(d,J＝6.6Hz),126.0,123.9(d,J＝14.0Hz),123.8(d,J＝14.0Hz),123.6(d,J＝94.6Hz),123.4(d,J＝94.0Hz),121.2,115.1(dd,J＝254.4,254.8Hz),112.6,111.7(d,J＝2.2Hz),109.6,105.3,83.5,80.0,79.9,79.9–79.6(m),77.1,72.7,67.5,63.0,41.5(t,J＝24.2Hz),27.0,26.9,26.4,25.5,14.1.31P NMR(243MHz,CDCl3)δ28.21.19F NMR(471MHz,CDCl3)δ-101.16(dd,J＝265.3,16.9Hz,1F),-107.49(dd,J＝265.3,39.9Hz,1F).HRMS:[M+Na]+m/z calcd for C45H45F2NaO11P+:853.2560,found:853.2562。
Example 21
1, 6-eneyne compound 1q (47.6mg, 0.2mmol) is used as a raw material, and the rest conditions are the same as those of the aboveExample 1 gave 67.4mg of the objective compound (compound 3q) in a yield of 60%.1H NMR(400MHz,CDCl3)δ7.58–7.48(m,6H),7.41–7.35(m,4H),7.30–7.23(m,2H),7.15–7.10(m,1H),6.92–6.87(m,2H),6.74–6.71(m,1H),6.63–6.60(m,1H),6.54–6.52(m,1H),5.40–5.37(m,1H),4.39–4.26(m,2H),3.43–3.32(m,1H),2.80–2.64(m,1H),1.32(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝32.3Hz),159.1,157.0(d,J＝237.7Hz),154.1(dd,J＝7.9,3.0Hz),135.8(d,J＝9.4Hz),132.6(d,J＝9.9Hz),132.5(d,J＝10.3Hz),132.3(d,J＝2.8Hz),132.2(d,J＝2.7Hz),131.4(d,J＝104.5Hz),131.0(d,J＝105.5Hz),130.8(d,J＝4.0Hz),129.8(d,J＝3.8Hz),129.4(d,J＝1.2Hz),129.3(d,J＝1.2Hz),128.5(d,J＝4.4Hz),128.4(d,J＝2.3Hz),128.4(d,J＝4.0Hz),126.2(d,J＝93.5Hz),125.2(dd,J＝14.2,9.5Hz),119.7(d,J＝25.3Hz),115.1(dd,J＝254.4,254.8Hz),112.3(d,J＝26.6Hz),111.7(d,J＝8.5Hz),80.5–80.4(m),63.0,41.5(t,J＝24.9Hz),14.1.31P NMR(243MHz,CDCl3)δ28.21.19F NMR(471MHz,CDCl3)δ-101.27(d,J＝265.3Hz,1F),-107.41(d,J＝265.3Hz,1F),-122.27(s,1F).HRMS:[M+H]+m/z calcd for C32H27F3O4P+:563.1594,found:563.1600。
Example 22
Using 1, 6-eneyne compound 1r (50.8mg, 0.2mmol) as a starting material and the same conditions as in example 1, 63.6mg of the objective compound (compound 3r) was obtained in 55% yield.1H NMR(400MHz,CDCl3)δ7.59–7.48(m,6H),7.42–7.35(m,4H),7.32–7.24(m,2H),7.16–7.11(m,2H),6.92–6.89(m,1H),6.73(d,J＝8.6Hz,1H),6.65–6.61(m,1H),6.53–6.51(m,1H),5.62–5.61(m,1H),4.39–4.25(m,2H),3.44–3.32(m,1H),2.79–2.65(m,1H),1.32(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.2(t,J＝32.3Hz),161.5,153.5(d,J＝7.9Hz),135.8(d,J＝9.1Hz),132.6(d,J＝9.5Hz),132.5(d,J＝7.5Hz),132.4,132.3(d,J＝2.6Hz),132.2(d,J＝2.7Hz),131.4(d,J＝104.5Hz),130.9(d,J＝105.6Hz),130.8(d,J＝3.8Hz),129.7(d,J＝4.9Hz),129.4(d,J＝1.2Hz),129.3(d,J＝1.5Hz),128.5(d,J＝2.4Hz),128.4(d,J＝2.1Hz),128.4(d,J＝2.3Hz),126.4(d,J＝94.6Hz),126.0,125.9(d,J＝14.7Hz),115.1(dd,J＝254.4,254.8Hz),112.3,80.6–80.4(m),63.0,41.5(t,J＝23.8Hz),14.1.31P NMR(243MHz,CDCl3)δ28.22.19F NMR(471MHz,CDCl3)δ-101.34(d,J＝265.5Hz,1F),-107.25(d,J＝265.5Hz,1F).HRMS:[M+H]+m/z calcd for C32H27F3O4P+:579.1298,found:579.1296。
Example 23
Using 1, 6-enyne compound 1s (49.0mg, 0.2mmol) as a starting material and the same conditions as in example 1, 52.3mg of the objective compound (compound 3s) was obtained with a yield of 46%.1H NMR(400MHz,CDCl3)δ7.59–7.50(m,7H),7.43–7.39(m,5H),7.25–7.22(m,1H),7.10(d,J＝8.0Hz,1H),6.83(d,J＝8.4Hz,1H),6.71(d,J＝8.1Hz,1H),6.58–6.49(m,2H),5.74(d,J＝8.0Hz,1H),4.36–4.25(m,2H),3.45–3.34(m,1H),2.79–2.65(m,1H),1.32(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.1(t,J＝32.2Hz),163.4,155.6(d,J＝6.6Hz),142.0(d,J＝9.5Hz),133.5,132.9(d,J＝8.1Hz),132.6(d,J＝2.5Hz),132.5(d,J＝2.8Hz),132.4(d,J＝6.4Hz),132.3(d,J＝6.4Hz),132.0(d,J＝4.3Hz),131.2(d,J＝105.2Hz),131.2–131.1(m),130.6(d,J＝103.6Hz),128.8(d,J＝7.8Hz),128.7(d,J＝8.0Hz),125.8,123.6(d,J＝13.9Hz),122.9(d,J＝93.9Hz),121.4,118.5,115.0(dd,J＝254.7,254.8Hz),111.2(d,J＝2.3Hz),111.9,79.8–79.7(m),63.0,41.3(t,J＝25.2Hz),14.1.31P NMR(243MHz,CDCl3)δ28.15.19F NMR(471MHz,CDCl3)δ-101.21(d,J＝265.4Hz,1F),-107.38(d,J＝265.5Hz,1F).HRMS:[M+H]+m/z calcd for C34H30F2O6P+:570.1640,found:570.1646。
Example 24
Using 1t (47.2mg, 0.2mmol) of the 1, 6-enyne compound as a starting material and the same conditions as in example 1, 43.7mg of the objective compound (compound 3t) was obtained in 39% yield.1H NMR(400MHz,CDCl3)δ7.83–7.77(m,2H),7.55–7.51(m,1H),7.47–7.42(m,2H),7.39–7.34(m,3H),7.24–7.18(m,3H),7.14–7.00(m,4H),6.79–6.72(m,2H),6.64–6.60(m,1H),6.14(d,J＝8.0Hz,1H),5.50–5.46(m,1H),4.31–4.26(m,2H),3.37–3.25(m,1H),2.67–2.52(m,1H),1.26(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.2(t,J＝32.2Hz),158.5(d,J＝6.8Hz),144.0,136.8(d,J＝9.5Hz),134.8(d,J＝14.0Hz),133.1(d,J＝101.5Hz),132.6(d,J＝9.2Hz),132.2(d,J＝2.2Hz),132.0(d,J＝9.9Hz),131.7(d,J＝104.8Hz),131.6(d,J＝4.0Hz),131.4(d,J＝3.3Hz),131.1(d,J＝91.3Hz),130.6,129.2,129.1(d,J＝4.6Hz),128.9(d,J＝12.2Hz),128.6(d,J＝5.7Hz),127.9(d,J＝12.1Hz),127.7(d,J＝1.8Hz),124.1,123.8,115.5(dd,J＝254.4,254.8Hz),63.0,46.8–46.7(m),41.8(t,J＝23.2Hz),14.0.31P NMR(243MHz,CDCl3)δ28.88.19F NMR(471MHz,CDCl3)δ-101.12(d,J＝263.0Hz,1F),-105.76(d,J＝263.1Hz,1F).HRMS:[M+H]+m/z calcd for C32H28F2O3PS+:561.1459,found:561.1458。
Example 25
Using 1, 6-eneyne compound 1u (74.6mg, 0.2mmol) as a starting material and the same conditions as in example 1, 48.8mg of the objective compound (compound 3u) was obtained with a yield of 35%.1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.1Hz,1H),7.62–7.56(m,2H),7.54–7.49(m,4H),7.46–7.41(m,2H),7.33–7.27(m,2H),7.27–7.14(m,5H),6.98(d,J＝8.1Hz,2H),6.93–6.89(m,1H),6.82–6.79(m,1H),6.69–6.64(m,1H),6.62–6.58(m,1H),5.68(d,J＝8.1Hz,1H),5.58(d,J＝7.4Hz,1H),4.45–4.29(m,2H),3.37–3.24(m,1H),3.12–3.00(m,1H),2.28(s,3H),1.39(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ163.9(t,J＝32.2Hz),153.1(d,J＝7.3Hz),144.9,144.0,132.8(d,J＝8.9Hz),132.4(d,J＝10.2Hz),132.3,131.5,132.0(d,J＝104.2Hz),132.0(d,J＝2.6Hz),130.9(d,J＝3.5Hz),130.6(d,J＝4.1Hz),130.1(d,J＝105.5Hz),129.7,129.1–128.9(m),128.7(d,J＝12.1Hz),128.3(d,J＝2.0Hz),128.1,127.9(d,J＝12.0Hz),126.6(d,J＝93.1Hz),126.3,125.4,119.6,115.6(t,J＝251.9Hz),63.3,60.4–60.2(m),41.7(t,J＝23.5Hz),21.6,14.0.31P NMR(243MHz,CDCl3)δ27.57(s).19F NMR(565MHz,CDCl3)δ-102.04(d,J＝248.6Hz,1F),-102.75(d,J＝280.5Hz,1F).HRMS:[M+H]+m/z calcd for C39H35F2NO5PS+:698.1936,found:698.1934。
Example 26
Using diarylphosphine oxide 2b (147.2mg, 0.64mmol) as a starting material and the same conditions as in example 1, 60.6mg of the objective compound (compound 3v) was obtained in 53% yield.1H NMR(400MHz,CDCl3)δ7.46–7.38(m,4H),7.26–7.22(m,2H),7.19–7.09(m,6H),6.94–6.91(m,1H),6.79(d,J＝8.1Hz,1H),6.60–6.55(m,2H),6.52–6.47(m,1H),5.77(d,J＝8.0Hz,1H),4.40–4.25(m,2H),3.47–3.36(m,1H),2.77–2.63(m,1H),2.37(s,6H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝32.5Hz),163.0,154.1(d,J＝7.5Hz),142.5(d,J＝2.9Hz),142.4(d,J＝2.8Hz),136.6(d,J＝9.2Hz),132.6(d,J＝9.8Hz),132.5,132.49(d,J＝9.9Hz),131.2(d,J＝4.0Hz),130.1(d,J＝4.3Hz),129.1(d,J＝9.1Hz),129.0(d,J＝8.5Hz),128.7(d,J＝106.3Hz),128.3(d,J＝107.7Hz),128.0(d,J＝2.0Hz),126.2,125.3(d,J＝93.4Hz),124.5(d,J＝14.3Hz),121.0,115.1(dd,J＝254.4,254.8Hz),111.4,79.7–79.6(m),62.9,41.5(t,J＝23.9Hz),21.8(d,J＝3.2Hz),14.1.31P NMR(243MHz,CDCl3)δ28.47.19F NMR(471MHz,CDCl3)δ-100.91(d,J＝265.1Hz,1F),-107.89(d,J＝265.0Hz,1F).HRMS:[M+H]+m/z calcd for C34H32F2O4P+:573.2001,found:573.2002。
Example 27
Using diarylphosphine oxide 2c (167.7mg, 0.64mmol) as a starting material and the same conditions as in example 1, 45.9mg of the objective compound (compound 3w) was obtained in a yield of 38%.1H NMR(400MHz,CDCl3)δ7.48–7.41(m,4H),7.26–7.22(m,2H),7.19–7.10(m,2H),6.93–6.91(m,1H),6.89–6.84(m,4H),6.79(d,J＝8.4Hz,1H),6.59–6.47(m,3H),5.77(d,J＝8.0Hz,1H),4.40–4.26(m,2H),3.84(s,3H),3.83(s,3H),3.47–3.36(m,1H),2.77–2.64(m,1H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.4(t,J＝32.3Hz),162.9,162.6(d,J＝2.9Hz),162.5(d,J＝2.9Hz),153.6(d,J＝7.7Hz),136.8(d,J＝9.3Hz),134.5(d,J＝9.9Hz),134.4(d,J＝11.0Hz),132.5,131.2(d,J＝4.0Hz),130.1(d,J＝3.4Hz),129.1(d,J＝17.1Hz),128.0(d,J＝1.9Hz),126.2,125.7(d,J＝95.6Hz),124.5(d,J＝14.3Hz),123.2(d,J＝110.9Hz),122.8(d,J＝111.7Hz),121.0,115.2(dd,J＝254.4,254.8Hz),114.0(d,J＝9.8Hz),113.9(d,J＝9.4Hz),111.4,79.7–79.6(m),62.9,55.5,41.5(t,J＝23.9Hz),14.1.31P NMR(243MHz,CDCl3)δ27.82.19F NMR(471MHz,CDCl3)δ-100.89(d,J＝264.9Hz,1F),-107.90(d,J＝265.0Hz,1F).HRMS:[M+H]+m/z calcd for C34H32F2O6P+:605.1899,found:605.1898。
Example 28
The same procedures used in example 1 were repeated except for using diarylphosphine oxide 2d (226.6mg, 0.64mmol) as a starting material to give 66.8mg of the objective compound (Compound No. 3X) in a yield of 48%.1H NMR(400MHz,CDCl3)δ7.69–7.59(m,12H),7.48–7.44(m,4H),7.41–7.36(m,2H),7.27–7.23(m,2H),7.22–7.17(m,1H),7.16–7.11(m,1H),7.01–6.99(m,1H),6.82(d,J＝8.1Hz,1H),6.66–6.63(m,2H),6.54–6.49(m,1H),5.83(d,J＝8.0Hz,1H),4.41–4.26(m,2H),3.59–3.42(m,1H),2.84–2.69(m,1H),1.31(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.3(t,J＝32.4Hz),163.0,144.8(d,J＝2.8Hz),144.7(d,J＝2.4Hz),140.0(d,J＝1.5Hz),136.3(d,J＝9.3Hz),133.1(d,J＝9.8Hz),133.0(d,J＝9.6Hz),132.8,131.2(d,J＝3.8Hz),130.3(d,J＝105.7Hz),130.2(d,J＝4.5Hz),130.0(d,J＝106.4Hz),129.3(d,J＝9.3Hz),129.1,128.4,128.2(d,J＝2.5Hz),127.4,127.1(d,J＝6.2Hz),127.0(d,J＝6.1Hz),126.3,124.5(d,J＝95.3Hz),124.4(d,J＝15.4Hz),121.1,115.2(dd,J＝254.4,254.8Hz),111.4,79.7–79.6(m),62.9,41.6(t,J＝23.8Hz),14.1.31P NMR(243MHz,CDCl3)δ28.14.19F NMR(471MHz,CDCl3)δ-100.90(d,J＝265.0Hz,1F),-107.71(d,J＝265.0Hz,1F).HRMS:[M+H]+m/z calcd for C44H36F2O4P+:697.2314,found:697.2308。
Example 29
Using diarylphosphine oxide 2e (172.8mg, 0.64mmol) as a starting material and the same conditions as in example 1, 70.9mg of the objective compound (compound 3y) was obtained in a yield of 58%.1H NMR(400MHz,CDCl3)δ7.49–7.41(m,4H),7.38–7.34(m,4H),7.32–7.27(m,2H),7.23–7.15(m,2H),6.93–6.90(m,1H),6.82(d,J＝8.0Hz,1H),6.59–6.50(m,3H),5.79(d,J＝8.0Hz,1H),4.40–4.26(m,2H),3.45–3.28(m,1H),2.78–2.63(m,1H),1.32(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ164.2(t,J＝32.3Hz),163.2,139.0(dd,J＝9.9,3.3Hz),135.8(d,J＝9.5Hz),133.9(d,J＝10.4Hz),133.7(d,J＝10.4Hz),133.1,131.2(d,J＝3.9Hz),130.1(d,J＝3.8Hz),129.9(d,J＝105.5Hz),129.7(d,J＝106.7Hz),129.6(d,J＝1.3Hz),129.5(d,J＝1.3Hz),128.9(d,J＝6.6Hz),128.8(d,J＝6.4Hz),128.5(d,J＝2.1Hz),126.3,124.1(d,J＝14.8Hz),123.1(d,J＝97.2Hz),121.2,115.1(dd,J＝254.4,254.8Hz),111.6,79.6–79.5(m),63.0,41.6(t,J＝23.4Hz),14.1.31P NMR(243MHz,CDCl3)δ26.94.19F NMR(471MHz,CDCl3)δ-101.03(d,J＝265.1Hz,1F),-107.63(d,J＝265.1Hz,1F).HRMS:[M+Na]+m/z calcd for C32H25Cl2F2NaO4P+:635.0728,found:635.0718。
The foregoing embodiments illustrate the principles, principal features and advantages of the invention, and it will be understood by those skilled in the art that the invention is not limited to the foregoing embodiments, which are merely illustrative of the principles of the invention, and that various changes and modifications may be made therein without departing from the scope of the principles of the invention.
Claims (7)
1. A tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl is characterized in that the structural general formula of the tetra-substituted alkenyl phosphine oxide compound containing difluoroalkyl is as follows:
wherein R is1Is H, methyl, fluorine or chlorine; r2Is H, methyl, ethyl, tert-butyl, phenyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, acetyl or cyano; r3Is H, methyl, methoxy, chlorine or phenyl; x is O, S or NTs.
2. The preparation method of the difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound as claimed in claim 1, which is characterized by comprising the following steps: adding 1, 6-eneyne compounds 1, ethyl difluoroiodoacetate, diaryl phosphine oxide compounds 2, a catalyst, a ligand and alkali into a solvent, stirring and reacting completely at 60-90 ℃ in an inert gas atmosphere, and performing post-treatment to obtain target products, namely, tetra-substituted alkenyl phosphine oxide compounds 3 containing difluoroalkyl, wherein the reaction equation in the preparation process is as follows:
wherein R is1Is H, methyl, fluorine or chlorine; r2Is H, methyl, ethyl, tert-butyl, phenyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, acetyl or cyano; r3Is H, methyl, methoxy, chlorine or phenyl; x is O, S or NTs;
the catalyst is trans-bis (triphenylphosphine) palladium dichloride (PdCl)2(PPh3)2) Palladium chloride (PdCl)2) Palladium trifluoroacetate (Pd (TFA))2) Bis (dibenzylideneacetone) palladium (Pd)2(dba)3) Palladium acetate (Pd (OAc)2) Or tetratriphenylphosphine palladium (Pd (PPh)3)4)；
The ligand is triphenylphosphine (PPh)3) 1,1' -bisdiphenylphosphinoferrocene (dppf) or 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene (xanthphos);
the alkali is potassium carbonate, potassium phosphate, sodium carbonate or cesium carbonate;
the solvent is 1, 4-dioxane, toluene, tetrahydrofuran or 1, 2-Dichloroethane (DCE).
3. The method of claim 2, wherein the compound is selected from the group consisting of: the dosage of the catalyst is 5 to 10 percent equiuv; the dosage of the ligand is 10 to 20 percent equiuv; the dosage of the alkali is 1-3 equiuv; the dosage of the ethyl difluoroiodoacetate is 1-3 equiv; the dosage of the diaryl phosphine oxide compound is 1-4 equiuv.
4. The method of claim 2, wherein the compound is selected from the group consisting of: the amount of the catalyst is 10% equiuv; the amount of the ligand is 20% equiuv; the amount of the alkali is 2 equiuv; the dosage of the difluoro iodoacetic acid ethyl ester is 2 equiuv; the dosage of the diaryl phosphine oxide compound is 3.2 equiuv.
5. The method of claim 2, wherein the compound is selected from the group consisting of: the reaction temperature in the preparation process is 80 ℃, and the reaction time is 10-24 h.
6. The method of claim 2, wherein the compound is selected from the group consisting of: the inert gas atmosphere is argon or nitrogen.
7. The method of claim 2, wherein the compound is selected from the group consisting of: the post-treatment comprises the following specific processes: extracting the reaction liquid after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, performing column separation after spin-drying, wherein a column-passing solvent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 3: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011419127.9A CN112552342A (en) | 2020-12-07 | 2020-12-07 | Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011419127.9A CN112552342A (en) | 2020-12-07 | 2020-12-07 | Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112552342A true CN112552342A (en) | 2021-03-26 |
Family
ID=75059574
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011419127.9A Pending CN112552342A (en) | 2020-12-07 | 2020-12-07 | Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112552342A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113603719A (en) * | 2021-08-16 | 2021-11-05 | 新乡医学院 | Difluoroalkyl substituted sulfur phosphate compound and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB939619A (en) * | 1961-09-01 | 1963-10-16 | Albright & Wilson Mfg Ltd | Aromatic phosphine oxides |
| WO2002064604A1 (en) * | 2001-02-14 | 2002-08-22 | Japan Science And Technology Corporation | Process for preparation of alkenylphosphine oxides or alkenylphosphinic esters |
| JP2002241386A (en) * | 2001-02-14 | 2002-08-28 | Japan Science & Technology Corp | Method for producing alkenylphosphine oxides |
| CN108456227A (en) * | 2018-04-18 | 2018-08-28 | 南京师范大学 | A kind of chloro- 3- cyclobutenyls phosphonate compound of bis- fluoro- 3- sulfonyls -2- of 1,1- and its synthetic method and application |
| CN108774263A (en) * | 2018-06-26 | 2018-11-09 | 广东工业大学 | A kind of synthetic method of allyl oxidation phosphine compound |
| CN109503658A (en) * | 2019-01-03 | 2019-03-22 | 南京师范大学 | The fluoro- 1,3- butadiene phosphonate ester compound of one kind (E) -3- aryl -1- and its synthetic method and application |
-
2020
- 2020-12-07 CN CN202011419127.9A patent/CN112552342A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB939619A (en) * | 1961-09-01 | 1963-10-16 | Albright & Wilson Mfg Ltd | Aromatic phosphine oxides |
| WO2002064604A1 (en) * | 2001-02-14 | 2002-08-22 | Japan Science And Technology Corporation | Process for preparation of alkenylphosphine oxides or alkenylphosphinic esters |
| JP2002241386A (en) * | 2001-02-14 | 2002-08-28 | Japan Science & Technology Corp | Method for producing alkenylphosphine oxides |
| CN108456227A (en) * | 2018-04-18 | 2018-08-28 | 南京师范大学 | A kind of chloro- 3- cyclobutenyls phosphonate compound of bis- fluoro- 3- sulfonyls -2- of 1,1- and its synthetic method and application |
| CN108774263A (en) * | 2018-06-26 | 2018-11-09 | 广东工业大学 | A kind of synthetic method of allyl oxidation phosphine compound |
| CN109503658A (en) * | 2019-01-03 | 2019-03-22 | 南京师范大学 | The fluoro- 1,3- butadiene phosphonate ester compound of one kind (E) -3- aryl -1- and its synthetic method and application |
Non-Patent Citations (5)
| Title |
|---|
| DA-PENG LI等: "Manganese(III)-Mediated Selective Diphenylphosphinoyl Radical Reaction of 1,4-Diaryl-1-butynes for the Synthesis of 2‑Phosphinoylated 3,4-Dihydronaphathalenes", 《J. ORG. CHEM.》 * |
| G. GANGADHARARAO等: "Unusual nitrogen based heterocycles via allenic intermediates from the reaction of propargyl alcohols with P(III) substrates", 《TETRAHEDRON》 * |
| PENG SHI等: "Palladium/silver reagent-promoted aryl phosphorylation:flexible synthesis of substituted-3-benzylidene-2-(2-(diphenylphosphoryl)-aryl)-isoindolin-1-one", 《RSC ADV.》 * |
| PENGBO ZHANG等: "Palladium-Catalyzed Cascade Difluoroalkylation and Phosphinoylation of 2‑Vinyloxy Arylalkynes: Selective Synthesis of Difluoroalkyl-Containing Tetrasubstituted Alkenylphosphine Oxides", 《J. ORG. CHEM.》 * |
| VENU SRINIVAS等: "To stay as allene or go further? Synthesis of novel phosphono-heterocycles and polycyclicsviapropargyl alcohols", 《CHEM. COMMUN.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113603719A (en) * | 2021-08-16 | 2021-11-05 | 新乡医学院 | Difluoroalkyl substituted sulfur phosphate compound and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gavryushin et al. | An efficient Negishi cross-coupling reaction catalyzed by nickel (II) and diethyl phosphite | |
| CN102844288B (en) | Carbon nano ring and preparation method thereof, with suitable as this carbon nano ring compound preparing raw material and preparation method thereof | |
| JP5803042B2 (en) | Monophosphorus ligands and their use in cross-coupling reactions | |
| CN108178770B (en) | Method for synthesizing α -amino boron compound | |
| CN105348321B (en) | One kind synthesis α, the method for α difluoro methylene alkenyl phosphonates | |
| Lightfoot et al. | A stereoselective synthesis of 1, 6-diphenyl-1, 3, 5-hexatrienes utilising 4, 4, 6-trimethyl-2-vinyl-1, 3, 2-dioxaborinane as a two-carbon alkenyl building block | |
| CN112552342A (en) | Difluoroalkyl-containing tetra-substituted alkenyl phosphine oxide compound and preparation method thereof | |
| CN111454286A (en) | Synthetic method of difluoroalkenyl boron compound | |
| CN110494439B (en) | Chiral biphenyl diphosphine ligand and preparation method thereof | |
| CN113603719A (en) | Difluoroalkyl substituted sulfur phosphate compound and preparation method thereof | |
| Maillard et al. | Chiral perfluorous analogues of MOP. Synthesis and applications in catalysis | |
| CN113402553A (en) | 2-alkyl-indole skeleton phosphine ligand and preparation method and application thereof | |
| CN101195641A (en) | Novel phosphine ligand, production and uses in catalytic reaction thereof | |
| Mahrwald et al. | Ti (OiPr) 4-Mediated nucleophilic substitution of propargylic esters | |
| CN108299340B (en) | Method for synthesizing 2-fluoro-N-substituted aryl acetamide compound | |
| CN113773201B (en) | Trifluoromethyl-containing spiro [4,5] decane compound and preparation method thereof | |
| CN108659028B (en) | (Z) -type fluoroalkyl alkenyl borate and preparation method and application thereof | |
| CN113651863B (en) | Unsaturated thioglycoside compound and selective synthesis method and application thereof | |
| CN113354500A (en) | Method for preparing 1, 5-diene derivative | |
| CN110551024B (en) | Preparation method of difluoro iodo olefin | |
| JP7418768B1 (en) | Method for producing diarylacetylene derivatives | |
| CN114315894B (en) | Chiral alpha-aryl phosphate, chiral alpha-aryl phosphine compound and synthesis thereof | |
| Ma | Palladium-Catalyzed Stereoselective CF Bond Activation of Gem-Difluoroalkenes and Copper-Mediated Trifluoromethylation of α-Diazo Compounds | |
| CN116947921A (en) | Method for preparing alkenyl phosphate compound | |
| CN115894556A (en) | Synthesis method of beta-fluoroallylphosphine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210326 |