CN111620911A - 手性螺环磷酸双铑配合物及其制备方法与应用 - Google Patents
手性螺环磷酸双铑配合物及其制备方法与应用 Download PDFInfo
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- CN111620911A CN111620911A CN202010502942.5A CN202010502942A CN111620911A CN 111620911 A CN111620911 A CN 111620911A CN 202010502942 A CN202010502942 A CN 202010502942A CN 111620911 A CN111620911 A CN 111620911A
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- 238000002360 preparation method Methods 0.000 title abstract description 8
- 238000010668 complexation reaction Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- -1 bis-rhodium phosphate Chemical compound 0.000 claims abstract description 27
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 12
- 239000010452 phosphate Substances 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 claims abstract description 3
- OPELWUSJOIBVJS-UHFFFAOYSA-N 3,3'-spirobi[1,2-dihydroindene] Chemical group C12=CC=CC=C2CCC11C2=CC=CC=C2CC1 OPELWUSJOIBVJS-UHFFFAOYSA-N 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 47
- 239000003054 catalyst Substances 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 5
- 230000037431 insertion Effects 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 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 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- 150000001347 alkyl bromides Chemical class 0.000 claims description 2
- 229910052796 boron Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 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
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 150000003961 organosilicon compounds Chemical class 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 abstract description 18
- 229910000147 aluminium phosphate Inorganic materials 0.000 abstract description 15
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 abstract description 9
- 238000006713 insertion reaction Methods 0.000 abstract description 7
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical group [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 abstract description 2
- 150000003377 silicon compounds Chemical class 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 239000010948 rhodium Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- 229910052703 rhodium Inorganic materials 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 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 5
- 238000001816 cooling Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000006276 transfer reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 1
- 241000029094 Acanthurus bahianus Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- SYTWTVZNCBCOHU-UHFFFAOYSA-N OBO.CC(C)(O)C(C)(C)O.CC(C)(O)C(C)(C)O Chemical compound OBO.CC(C)(O)C(C)(C)O.CC(C)(O)C(C)(C)O SYTWTVZNCBCOHU-UHFFFAOYSA-N 0.000 description 1
- 239000006004 Quartz sand Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000003723 Smelting Methods 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- USLKCMBGQFYUFI-UHFFFAOYSA-N dichloromethane;tribromoborane Chemical compound ClCCl.BrB(Br)Br USLKCMBGQFYUFI-UHFFFAOYSA-N 0.000 description 1
- OIKHZBFJHONJJB-UHFFFAOYSA-N dimethyl(phenyl)silicon Chemical compound C[Si](C)C1=CC=CC=C1 OIKHZBFJHONJJB-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000001282 organosilanes Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WMFZVLIHQVUVGO-UHFFFAOYSA-N phenyl-(4-phenylphenyl)methanol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(O)C1=CC=CC=C1 WMFZVLIHQVUVGO-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005303 weighing 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium compounds
- C07F15/008—Rhodium compounds without a metal-carbon linkage
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2213—At least two complexing oxygen atoms present in an at least bidentate or bridging ligand
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
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Abstract
本发明涉及一种手性螺环磷酸双铑配合物及其制备方法和应用。该手性螺环磷酸双铑配合物是具有式I所示的化合物,能够通过具有手性螺双二氢茚骨架的磷酸与醋酸铑反应制备,其主要结构特点是四个手性螺环磷酸阴离子配位到两个铑原子上。该配合物可以催化双芳基重氮衍生的卡宾对硅氢键的插入反应,制备手性有机硅化合物。
Description
技术领域
本发明属于有机合成技术领域,涉及一种手性螺环磷酸双铑配合物及其制备方法与应用,具体涉及一类具有螺双二氢茚骨架的手性螺环磷酸双铑配合物的制备方法和其在卡宾对硅氢键的不对称插入反应方面的应用。
背景技术
手性化合物的一对对映异构体通常表现出不同的生物活性,因而选择性地获得单一构型的手性化合物成为合成化学家普遍关注的问题[Nicolaou,K.C.;Montagnon,T.Molecules that Changed the World;Wiley-VCH,2008]。不对称催化合成因其具有手性增殖、效率高等优点,已经成为获得手性化合物最为有效的方法之一[Jacobsen,E.N.;Pfaltz,A.;Yamamoto,H.Comprehensive Asymmetric Catalysis I-III Vol.1,Springer,1999]。不对称催化反应的手性诱导来源于手性催化剂,因此发展新型的手性催化剂一直是不对称催化反应研究的重要内容。手性双铑催化剂是一类非常优秀的催化剂,特别是在卡宾不对称转移反应,如环丙烷化反应,碳氢键插入反应,叶立德形成及转化反应中表现出优秀的催化活性及手性诱导效果[Hansen,J.;Davies,H.M.Coord.Chem.Rev.2008,252,545.;Deng,Y.;Qiu,H.;Srinivas,H.D.;Doyle,M.P.Curr.Org.Chem.2016,20,61.;Davies,H.M.L.;Liao,K.Nat.Rev.Chem.2019,3,347.]。在过去几十年里,化学家们合成了多种手性双铑催化剂,然而,真正获得广泛应用的并不多,主要是手性酰胺双铑催化剂和手性羧酸双铑催化剂。有限的结构类型阻碍了该类催化剂更为广泛的应用。因此,发展新型手性双铑催化剂具有重要的意义。1992年以来,人们发展了多种联芳环骨架手性磷酸作为配体的双铑催化剂,并且将其应用于很多卡宾转移反应中,然而对映选择性并不理想[McCarthy,N.;McKervey,M.-A.;Ye,T.;McCann,M.;Murphy,E.;Doyle,M.-P.Tetrahedron Lett.1992,33,5983.;Pirrung,M.C.;Zhang,J.Tetrahedron Lett.1992,33,5987.;Hrdina,R.;Guénée,L.;Moraleda,D.;Lacour,J.Organometallics 2013,32,473.]。
手性有机硅是重要的合成砌块[Fleming,I.;Barbero,A.;Walter,D.Chem.Rev.1997,97,2063.]。过渡金属催化卡宾对硅氢键的不对称插入反应是合成手性有机硅化合物的重要手段。目前,该类反应研究主要集中于带有吸电子取代基(酯基、酰胺、氰基等)的卡宾,这就导致反应类型局限,插入产物结构单一[Keipour,H.;Carreras,V.;Ollevier,T.Org.Biomol.Chem.2017,15,5441.]。然而,不含吸电子取代基的卡宾,如双芳基卡宾,芳基烷基卡宾,芳基炔基卡宾等的不对称硅氢键插入反应报道很少,特别是双芳基卡宾类型,由于其两个芳基空间位阻差异小,难以区分,因而难以获得高对映选择性。
发明内容
本发明的目的在于提供一类新型手性螺环磷酸双铑配合物及其制备方法和应用。相对于文献报道的酰胺和羧酸类型的双铑配合物,这类手性螺环磷酸双铑配合物具有更强的路易斯酸性。就空间结构而言,由于手性螺环磷酸具有C2对称性,这类手性螺环磷酸双铑配合物具有D4对称性,骨架刚性高,其形成的金属卡宾中间体在进行后续不对称转化时,过渡态构象更少,有利于手性控制。
本发明提供的手性螺环磷酸双铑配合物,是具有式I的化合物或所述化合物的对映体、消旋体。
其中,n=0~3,R1、R2分别独立选自C1~C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基,所述的苯基上的取代基为C1~C10的烃基、烷氧基,取代基数量为1~5,杂芳基为呋喃基、噻吩基或吡啶基,R1、R2可以相同也可以不同。
R3、R4、R5、R6分别独立选自H、C1~C10烷基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基,所述的苯基上的取代基为C1~C10的烃基、烷氧基,取代基数量为1~5,杂芳基为呋喃基、噻吩基或吡啶基;或C1~C10烷氧基;或R3~R4、R4~R5、R5~R6为C3~C7脂肪环;或R3~R4、R5~R6为芳香环;R3、R4、R5、R6可以相同也可以不同;
本发明提供手性螺环磷酸双铑配合物的制备方法,其特征在于:以式1所示的消旋或旋光活性的7,7′-二甲氧基-1,1′-螺双二氢茚类化合物为起始原料,经过下述反应式合成:
在有机溶剂、硼试剂和铱催化剂及含氮配体存在的条件下,具有式1所示的化合物在反应器中反应4~12小时制备得到式2a所示的化合物;在有机溶剂,溴化钠和双氧水存在条件下,式1所示的化合物在反应器中反应12~24小时制备得到式2b所示的化合物;式2a所示的化合物在钯催化剂下与芳基或烷基溴代物反应得到式3所示的化合物;式2b所示的化合物在钯催化剂下与芳基或烷基硼酸反应得到式3所示的化合物。
在有机溶剂、三溴化硼或二乙氨基乙硫醇钠存在的条件下,式3所示的化合物脱除甲基得到4所示的化合物;在有机溶剂存在条件下,式4所示的化合物与三氯氧磷反应得到磷酰氯,然后水解得到式5所示的化合物。
式5所示化合物与醋酸铑反应,交换掉醋酸根得到式I所示的化合物。
在上述合成方法中,所述的有机溶剂可以是甲苯、四氢呋喃、环戊基甲基醚、二氯甲烷、N,N-二甲基甲酰胺、吡啶、氯苯中的一种或其中几种的混合溶剂。
本发明所述的手性螺环磷酸双铑的应用,其特征是用于催化卡宾对硅氢键的不对称插入反应,经过下述反应式:
其中:R为烷基,芳基,R1,R2分别独立选自烷基、苯基、取代苯基、2-萘基,酯基,所述的苯基上的取代基为烷基、芳基,R1、R2不同。
作为优先方案,其特征是在二氯甲烷溶剂中,手性螺环磷酸双铑配合物I为手性催化剂,有机硅烷为反应试剂,将重氮化合物溶液滴加至反应体系中就可得到高对映选择性的手性硅烷化合物。
作为更进一步的优先方案,其特征是双芳基重氮底物与催化剂的比为(1000∶1~100∶1);底物浓度为0.1M;反应温度为0℃。
作为更进一步的优先方案,手性磷酸双铑配合物选自如下化合物的对映体、消旋体:
本发明提供的手性螺环磷酸双铑配合物,主要结构特征是具有手性螺双二氢茚骨架和具有磷酸双铑中心,可催化卡宾对硅氢键的不对称插入反应,取得高活性以及高对映选择性(高达99%ee)。
具体实施方式
下面结合实施实例对本发明作进一步详细、完整的说明,列出的实施实例将有助于理解本发明,但不应将此理解为本发明上述主题的范围仅限于以下的实例,凡基于本发明上述内容所实现的技术均属于本发明的范围。
一般说明:
实施实例中使用了缩写,其含义如下:
Me是甲基,tBu是叔丁基,Ph是苯基,THF是四氢呋喃,DCM是二氯甲烷,PE是石油醚,EA是乙酸乙酯,B2pin2是双联频哪醇硼酸酯。TLC是薄层色谱,NMR是核磁共振,HRMS是高分辨质谱。
所用溶剂在使用前用标准方法提纯,干燥;所用试剂均为市售或按照已有文献方法合成得到,并在使用前提纯。
实施例1:
(S)-5,5′-二(频哪醇硼酸酯基)-7,7′-二(甲氧基)-1,1′-螺双二氢茚(2a)的合成
在装有磁力搅拌子的120mL干燥的封管中加入化合物1(2.3g,8.0mmol),双联频哪醇硼酸酯(B2pin2,4.5g,17.6mmol),[Ir(OMe)(cod)]2(212mg,0.32mmol),及配体(151mg,0.64mmol)。将体系置换为氩气氛围,用注射器加入干燥的四氢呋喃(30mL),搅拌均匀。油浴加热至80℃反应8小时,TLC监测反应完全。冷却至室温,用旋转蒸发仪脱除溶剂,残余物经硅胶柱层析(二氯甲烷)得到3.8g粗产物,粗收率90%,在重蒸的石油醚中加热重结晶,得到纯的白色固体2a,收率70%,熔点:190-192℃,[α]D 25=-34.0(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.34(s,2H,ArH),7.04(s,2H,ArH),3.56(s,6H,2OCH3),3.10-2.90(m,4H,2CH2),2.33-2.25(m,2H,CH2),2.16-2.10(m,2H,CH2),1.34(s,24H,8CH3).
13C NMR(101MHz,CDCl3)
δ156.1,145.0,140.5,123.6,114.3,83.6,59.5,55.3,38.5,31.3,24.9,24.9.
11B NMR(128MHz,CDCl3)
δ33.9.
HRMS(ESI)
Calcd for[C31H42B2O6,M+Na]+:555.3065,Found:555.3070.
实施例2:
(S)-5,5′-二苯基-7,7′-二(甲氧基)-1,1′-螺双二氢茚(3a)的合成
向250mL三口圆底烧瓶中依次加入化合物2a(1.3g,2.5mmol),溴苯(PhBr,2.36g,15.0mmol)和四三苯基膦钯(Pd(PPh3)4,443mg,0.375mmol),置换氩气后,依次加入甲苯(30mL),乙醇(14mL)和碳酸钾水溶液(1N,20mL),冷冻脱气,之后,将反应体系置于90℃油浴中加热搅拌过夜。TLC监测反应完全后,冷却至室温并加入乙酸乙酯稀释,分液,乙酸乙酯萃取水相(3×20mL),合并有机相并用饱和食盐水洗涤,无水硫酸镁干燥。抽滤,脱溶后经硅胶柱层析(石油醚/二氯甲烷=4∶1),得到0.8g白色固体3a,收率78%,熔点:58-60℃,[α]D 25=-1.4(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.61(d,J=7.3Hz,4H,ArH),7.41(t,J=7.0Hz,4H,ArH),7.32(d,J=6.2Hz,2H,ArH),7.10(s,2H,ArH),6.85(s,2H,ArH),3.61(s,6H,2OCH3),3.24-2.99(m,4H,2CH2),2.50-2.38(m,2H,CH2),2.30-2.16(m,2H,CH2).
13C
NMR(101MHz,CDCl3)
δ156.7,146.0,142.0,141.3,136.1,128.7,127.2,127.0,115.9,108.1,58.9,55.4,39.2,31.8.
HRMS(ESI)
Calcd for[C31H28O2,M+Na]+:455.1987,Found:455.1985.
实施例3:
(S)-5,5′-二苯基-1,1′-螺双二氢茚-7,7′-二酚(4a)的合成
在装有磁力搅拌的250mL干燥的三口瓶中加入化合物3a(0.85g,2.0mmol),置换为氩气氛围,用注射器加入干燥的二氯甲烷(20mL),搅拌均匀。将体系降温至-78℃,缓慢滴加三溴化硼的二氯甲烷溶液(BBr3,1M,15mL),自然恢复室温,搅拌过夜。TLC监测反应完全,加入二氯甲烷稀释反应体系,合并有机相,依次用饱和亚硫酸氢钠溶液、饱和碳酸氢钠溶液和饱和食盐水洗涤,无水硫酸镁干燥。抽滤,脱溶后经硅胶柱层析(石油醚/二氯甲烷=1∶1),得到0.46g白色固体4a,收率57%,熔点:101-102℃。[α]D 25=+40.6(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.53(d,J=7.8Hz,4H,ArH),7.42-7.34(m,4H,ArH),7.34-7.26(m,2H,ArH),7.10(s,2H,ArH),6.90(s,2H,ArH),4.85(s,2H,2OH),3.15-2.92(m,4H,2CH2),2.39-2.14(m,4H,2CH2).
13C
NMR(101MHz,CDCl3)
δ153.0,146.6,143.5,140.9,129.9,128.8,127.5,127.2,116.7,113.4,57.2,37.8,31.4.
HRMS(ESI)
Calcd for[C29H24O2,M+Na]+:427.1674,Found:427.1673.
实施例4:
(S)-5,5′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸(5a)的合成
在50mL三口圆底瓶中加入化合物4a(460mg,1.2mmol),置换氮气后,加入吡啶(4mL)搅拌溶解,冰浴冷却下小心滴加三氯氧磷(370mg,2.4mmol),滴完后置于100℃油浴中加热10小时。TLC监测二酚反应完全后,自然恢复室温后缓慢滴加水(4mL),滴完后置于90℃油浴中继续加热10小时。冰浴冷却下缓慢滴加浓盐酸(20mL),滴完后保持搅拌1小时。二氯甲烷萃取水相(3×20mL),合并有机相,减压脱除溶剂,得到粗产品,柱层析(甲醇/二氯甲烷=1∶5)得到440mg白色固体5a,收率79%,熔点:275-277℃,[α]D 25=-395(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ12.35(s,1H,OH),7.48(d,J=7.2Hz,4H,ArH),7.38-7.17(m,10H,ArH),3.20-3.05(m,2H,CH2),2.88-2.77(m,2H,CH2),2.35-2.25(m,2H,CH2),2.15-1.92(m,2H,CH2).
13C
NMR(101MHz,CDCl3)
δ147.0(d,J=2.2Hz),145.5(d,J=7.6Hz),142.3(d,J=2.0Hz),139.9,137.9(d,J=3.6Hz),128.6,127.3,127.1,121.6,120.1(d,J=3.3Hz),58.8,38.4,30.6.
31P
NMR(162MHz,CDCl3)
δ-9.2(s).
HRMS(ESI)
Calcd for[C29H23O4P,M+Na]+:489.1232,Found:489.1230.
实施例5:
(S)-5,5′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ia)的合成
在100mL干燥的装有索氏提取器(内含石英砂和无水碳酸钠1∶1混合物)的两口圆底烧瓶中依次加入化合物5a(1.4g,1.5mmol)、醋酸双铑(120mg,0.18mmol),置换为氩气氛围,用注射器加入干燥氯苯(25mL),搅拌均匀,加热回流。反应24小时后停止加热,减压脱溶后柱层析(二氯甲烷),得到500mg粗产物Ia,在二氯甲烷和甲醇的混合液中重结晶得到260mg淡绿色透明针状晶体,收率50%,熔点:>300℃,[α]D 25=+289(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.64(s,8H,ArH),7.42-7.37(m,16H,ArH),7.33(s,8H,ArH),7.22-7.13(m,24H,ArH),3.17-3.06(m,8H,4CH2),2.94(s,3H,H2O),2.92-2.80(m,8H,4CH2),2.33-2.24(m,8H,4CH2),2.07-1.95(m,14H,4CH2+(CH3)2(CO)).
13C
NMR(101MHz,CDCl3)
δ146.6(p,J=3.3Hz),146.3,141.7,140.2,138.4,128.5,127.1,127.0,120.8,120.8,58.6,38.6,30.9((CH3)2(CO)),30.7.
31P
NMR(162MHz,CDCl3)
δ6.6(s).
HRMS(MALDI)
Calcd for[C116H88O16P4Rh2,M+Na]+:2090.3064,Found:2090.3034.
(以下实施例中只是改变反应物,操作过程同实例2-5,制备化合物5b-5h及化合物Ib-Ih)。
实施例6:
(S)-5,5′-二(4-三氟甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5b)和(S)-5,5′-二(4-三氟甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ib)的合成
具体操作参考实例2-5。
(S)-5,5′-二(4-三氟甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5b)
Ar=4-CF3C6H4
灰白色固体,收率91%,熔点:>280℃,[α]D 21=-393(c 0.2,CHCl3)。
1H
NMR(400MHz,DMSO-d6)
δ7.92(d,J=7.9Hz,4H,ArH),7.82(d,J=8.1Hz,4H,ArH),7.54(s,2H,ArH),7.30(s,2H,ArH),3.26-3.14(m,2H,CH2),2.95-2.86(m,2H,CH2),2.42-2.34(m,2H,CH2),2.01-1.83(m,2H,CH2).
31P
NMR(162MHz,DMSO-d6)
δ-6.6(br).
19F
NMR(376MHz,DMSO-d6)
δ-61.3(s,3F).
HRMS(ESI)
Calcd for[C33H26F6O4P,M+H]+:603.1160,Found:603.1158.
(S)-5,5′-二(4-三氟甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ib)
Ar=4-CF3C6H4
浅绿色晶体,收率30%,熔点:>300℃,[α]D 20=+122(c 0.4,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.61(s,8H,ArH),7.50(d,J=8.4Hz,16H,ArH),7.45(d,J=8.4Hz,16H,ArH),7.40(s,8H,ArH),3.25-3.08(m,8H,4CH2),2.95-2.83(m,8H,4CH2),2.42-2.30(m,8H,4CH2),2.02-1.89(m,8H,4CH2).
13C
NMR(101MHz,CDCl3)
δ147.0,143.4,140.5,139.2,129.3,129.0,127.2,125.5(q,J=3.7Hz),125.4,122.9,121.1,58.6,38.6,30.6.
31P
NMR(162MHz,CDCl3)
δ6.5(s).
19F
NMR(376MHz,CDCl3)
δ-62.9(s,3F).
HRMS(ESI)
Calcd for[C124H80F24O16P4Rh2,M+Na]+:2634.2055,Found:2634.2056.
实施例7:
(S)-5,5′-二(4-(4-叔丁基苯基)苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5c)和(S)-5,5′-二(4-(4-叔丁基苯基)苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ic)的合成
具体操作参考实例2-5。
(S)-5,5′-二(4-(4-叔丁基苯基)苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5c)
Ar=4-(4-tBuC6H4)C6H4
白色固体,收率88%,熔点:>300℃。
HRMS(ESI)
Calcd for[C49H47O4P,M+Na]+:753.3110,Found:753.3108.
(S)-5,5′-二(4-(4-叔丁基苯基)苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ic)
Ar=4-(4-tBuC6H4)C6H4
浅绿色固体,收率53%,熔点:>320℃,[α]D 21=+22.4(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.60(s,8H,ArH),7.54-7.36(m,72H,ArH),3.19-3.02(m,8H,4CH2),2.91-2.79(m,8H,4CH2),2.36(s,3H,CH3O),2.38-2.27(m,8H,4CH2),2.16-2.02(m,8H,2CH2),1.36(s,72H,24CH3).
13C
NMR(101MHz,CDCl3)
δ150.1,146.7,146.4,141.1,139.6,138.8,138.5,137.8,127.3,127.0,126.5,125.7,121.0,120.3,58.6,38.6,34.5,31.4,30.8.
31P
NMR(162MHz,CDCl3)
δ5.8(s)(methanol in coordination sphere).
HRMS(ESI)
Calcd for[C196H184O16P4Rh2,M+Na]+:3148.0610,Found:3148.0600.
实施例8:
(S)-5,5′-二(2-萘基)-1,1′-螺双二氢茚-7,7′-磷酸(5d)和(S)-5,5′-二(2-萘基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Id)的合成
具体操作参考实例2-5。
(S)-5,5′-二(2-萘基)-1,1′-螺双二氢茚-7,7′-磷酸(5d)
白色固体,收率95%,熔点:>300℃。
1H
NMR(400MHz,DMSO-d6)
δ8.30(s,2H,ArH),8.10-8.01(m,4H,ArH),8.00-7.96(m,2H,ArH),7.93-7.89(m,2H,ArH),7.66(s,2H,ArH),7.61-7.50(m,4H,ArH),7.44(s,2H,ArH),3.32-3.19(m,2H,CH2),3.09-2.98(m,2H,CH2),2.50-2.40(m,2H,CH2),2.05-1.93(m,2H,CH2).
31P
NMR(162MHz,DMSO-d6)
δ-11.3(br).
HRMS(ESI)
Calcd for[C37H27O4P,M+H]+:567.1725,Found:567.1725.
(S)-5,5′-二(2-萘基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Id)
浅绿色固体,收率62%,熔点:>300℃,[α]D 21=+515(c 0.5,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.96(d,J=14.9Hz,16H,ArH),7.75(d,J=7.7Hz,8H,ArH),7.68(q,J=8.5Hz,16H,ArH),7.51(s,8H,ArH),7.46(d,J=7.5Hz,8H,ArH),7.42-7.31(m,16H,ArH),3.48(s,3H,CH3O),3.10-2.96(m,8H,4CH2),2.72-2.64(m,8H,4CH2),2.52(s,1H,OH),2.21-2.12(m,8H,4CH2),1.91-1.75(m,8H,4CH2).
13C
NMR(101MHz,CDCl3)
δ146.8,146.6,141.3,138.7,137.2,133.6,132.6,128.3,128.1,127.4,125.9,125.6,125.2,121.1,120.6,58.5,51.8(CH3OH),38.6,30.8.
31P
NMR(162MHz,CDCl3)
δ6.6(s)(methanol in coordination sphere).
HRMS(ESI)
Calcd for[C148H104O16P4Rh2,M+Na]+:2490.4316,Found:2490.4314.
实施例9:
(S)-5,5′-二(3,5-二甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5e)和(S)-5,5′-二(3,5-二甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ie)的合成
具体操作参考实例2-5。
(S)-5,5′-二(3,5-二甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸(5e)
Ar=3,5-Me2C6H3
白色固体,收率90%,熔点:>300℃;[α]D 25=-382(c 0.5,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.40-7.23(m,4H,ArH),7.15(s,4H,ArH),6.94(s,2H,ArH),3.21-3.08(m,2H,CH2),2.93-2.81(m,2H,CH2),2.41-2.21(m,14H,CH2+4CH3),2.11-2.01(m,2H,CH2).
13C
NMR(101MHz,CDCl3)
δ146.9,145.5,142.8,140.0,138.2,137.8,129.2,125.1,121.7,120.2,58.8,38.6,30.7,21.4.
31P
NMR(162MHz,CDCl3)
δ-7.3(s).
HRMS(ESI)
Calcd for[C33H31O4P,M+Na]+:545.1858,Found:545.1856.
(S)-5,5′-二(3,5-二甲基苯基)-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ie)
Ar=3,5-Me2C6H3
绿色晶体,收率30%,熔点:>320℃;[α]D 25=+172(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.42(s,8H,ArH),7.25(s,8H,ArH),7.12-7.01(m,16H,ArH),6.84(s,8H,ArH),3.12-2.98(m,8H,4CH2),2.83(s,2H,H2O),2.81-2.70(m,8H,4CH2),2.30-2.21(m,8H,4CH2),2.15(s,48H,16CH3),2.00-1.87(m,8H,4CH2).
13C
NMR(101MHz,CDCl3)
δ146.7,146.0,141.6,140.2,138.2,137.9,128.6,124.9,121.1,120.6,58.6,38.6,30.8,21.3.
31P
NMR(162MHz,CDCl3)
δ5.3(s).
HRMS(MALDI)
Calcd for[C132H120O16P4Rh2,M+Na]+:2314.5568,Found:2314.5550.
实施例10:
(S)-4,4′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸(5f)和(S)-4,4′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸双铑(If)的合成
具体操作参考实例4-5。
(S)-4,4′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸(5f)
白色固体,收率84%,熔点:209-211℃;[α]D 25=-224(c 0.5,CHCl3)。
1H
NMR(400MHz,DMSO-d6)
δ7.54(d,J=7.6Hz,4H,ArH),7.50-7.43(m,4H,ArH),7.39-7.34(m,2H,ArH),7.29(d,J=8.3Hz,2H,ArH),7.06(d,J=8.3Hz,2H,ArH),3.47-3.27(m,2H,CH2),2.72-2.62(m,2H,CH2),2.50(s,2H,DMSO),2.45-2.38(m,2H,CH2),1.92-1.82(m,2H,CH2).
13C
NMR(101MHz,DMSO-d6)
δ146.1,143.8,140.5(d,J=3.5Hz),140.2,135.6,129.0,128.9,128.9,127.6,122.9,59.6,38.6,30.7.
31P
NMR(162MHz,DMSO-d6)
δ-11.2(s).
HRMS(ESI)
Calcd for[C29H23O4P,M+Na]+:489.1232,Found:489.1230.
(S)-4,4′-二苯基-1,1′-螺双二氢茚-7,7′-磷酸双铑(If)
深绿色固体,收率95%,熔点:>320℃,[α]D 25=+143(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.48-7.36(m,31H,ArH),7.35-7.27(m,16H,ArH),7.19(d,J=8.4Hz,9H,ArH),3.86(s,1H,OH),3.43(s,3H,CH3O),3.30-3.12(m,8H,4CH2),2.81-2.71(m,8H,4CH2),2.38-2.28(m,8H,4CH2),2.11-1.98(m,8H,4CH2).
13C
NMR(101MHz,CDCl3)
δ145.7,143.4,140.4,139.7,136.3,129.5,128.7,128.3,127.0,122.8,59.7,38.3,30.8.
31P
NMR(162MHz,CDCl3)
δ5.9(s).
HRMS(MALDI)
Calcd for[C116H88O16P4Rh2,M+Na]+:2090.3064,Found:2090.3030.
实施例11:
(S)-4,4′-二溴-1,1′-螺双二氢茚-7,7′-磷酸(5g)和(S)-4,4′-二溴-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ig)的合成
具体操作参考实例4-5。
(S)-4,4′-二溴-1,1′-螺双二氢茚-7,7′-磷酸(5g)
白色固体,收率80%,熔点:186-188℃;[α]D 25=-211(c 0.5,CHCl3)。
1H
NMR(400MHz,CD3OD)
δ7.40(d,J=8.2Hz,2H,ArH),6.95(d,J=8.2Hz,2H,ArH),5.02(s,1H,OH),3.31(s,1H,CH3O),3.11-2.98(m,2H,CH2),2.90-2.78(m,2H,CH2),2.38-2.28(m,2H,CH2),1.98-1.89(m,2H,CH2).
13C
NMR(101MHz,CD3OD)
δ147.1(d,J=7.9Hz),145.2(d,J=2.0Hz),141.6(d,J=3.2Hz),130.9(d,J=2.1Hz),124.1(d,J=3.1Hz),115.0(d,J=3.1Hz),61.3,37.2,31.6.
31P
NMR(162MHz,CD3OD)
δ-9.8(s).
HRMS(ESI)
Calcd for[C17H13Br2O4P,M-H]-:470.8819,Found:470.8830.
(S)-4,4′-二溴-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ig)
深绿色固体,收率85%,熔点:>320℃,[α]D 25=+148(c 1.0,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.27(d,J=8.6Hz,8H,ArH),6.89(d,J=8.6Hz,8H,ArH),3.35(s,3H,CH3O),3.04-2.95(m,8H,4CH2),2.94-2.84(m,8H,4CH2),2.28-2.21(m,8H,4CH2),2.02-1.92(m,8H,4CH2).
13C
NMR(101MHz,CDCl3)
δ145.8,145.2(p,J=3.8Hz),140.6,132.1,124.1,117.1,61.4,37.6,32.1.
31P
NMR(162MHz,CDCl3)
δ4.5(s)(methanol in coordination sphere).
HRMS(MALDI)
Calcd for[C68H48Br8O16P4Rh2,M+Na]+:2112.3286,Found:2112.3303.
实施例12:
(R)-4,4′-二十二烷基-1,1′-螺双二氢茚-7,7′-磷酸(5h)和(R)-4,4′-二十二烷基-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ih)的合成
具体操作参考实例4-5。
(R)-4,4′-二十二烷基-1,1′-螺双二氢茚-7,7′-磷酸(5h)
无色油状液体,收率65%。
HRMS(ESI)
Calcd for[C41H63O4P,M-H]-:649.4386,Found:649.4388.
(R)-4,4′-二十二烷基-1,1′-螺双二氢茚-7,7′-磷酸双铑(Ih)
浅绿色固体,收率70%,熔点:260-265℃,[α]D 21=-135(c 0.5,CHCl3)。
1H
NMR(400MHz,CDCl3)
δ7.13-7.04(m,8H,ArH),6.92-6.87(m,8H,ArH),2.95-2.83(m,8H,4CH2),2.81-2.68(m,8H,4CH2),2.57-2.42(m,16H,8CH2),2.24-2.14(m,8H,4CH2),2.03-1.89(m,8H,4CH2),1.58-1.48(m,16H,8CH2),1.34-1.23(m,144H,72CH2),0.88(t,J=6.4Hz,24H,8CH3).
13C
NMR(101MHz,CDCl3)
δ144.6-144.2(m),143.5(t,J=6.0Hz),139.0-138.8(m),135.9(t,J=7.6Hz),128.5,122.3,59.4,38.0,32.9,31.9,30.1(2C signal),29.7,29.6(2C signal),29.5,29.3,28.9,22.7,14.1.
31P
NMR(162MHz,CDCl3)
δ5.9(s).
HRMS(ESI)
Calcd for[C164H248O16P4Rh2,M+Na]+:2827.5585,Found:2827.5575.
实施例13:
手性螺环磷酸双铑催化双芳基卡宾的不对称硅氢键插入反应。
在氩气氛围下,将苯基二甲基硅烷(32.7mg,0.24mmol)和手性螺环磷酸双铑(S)-Ia的二氯甲烷溶液(0.42mg,0.0002mmol,2mL)加入干燥的25mL Schlenk管。将其置于冰水浴中降温至0℃,使用注射器将双芳基重氮甲烷的二氯甲烷溶液(0.2mmol,1mL)滴加至反应体系中,用时3分钟。滴加完之后,待重氮颜色褪去,减压脱溶,硅胶柱层析(石油醚/乙酸乙酯=50∶1,v/v)得到目标产物,称重计算收率。使用高效液相色谱分析目标产物的光学纯度,所得实验结果见表1。
表1.手性螺环磷酸双铑(S)-Ia催化双芳基卡宾的不对称硅氢键插入反应
Claims (5)
1.一种手性螺环磷酸双铑配合物,是具有通式I的化合物或所述化合物的对映体、消旋体。
其中,n=0~3,R1、R2分别独立选自C1~C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基,所述的苯基上的取代基为C1~C10的烃基、烷氧基,取代基数量为1~5,杂芳基为呋喃基、噻吩基或吡啶基,R1、R2可以相同也可以不同。
R3、R4、R5、R6分别独立选自H、C1~C10烷基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基,所述的苯基上的取代基为C1~C10的烃基、烷氧基,取代基数量为1~5,杂芳基为呋喃基、噻吩基或吡啶基;或C1~C10烷氧基;或R3~R4、R4~R5、R5~R6并为C3~C7脂肪环;或R3~R4、R5~R6为芳香环;R3、R4、R5、R6可以相同也可以不同。
3.根据权利要求1和2所述的手性螺环磷酸双铑配合物的制备方法,其特征在于:以具有手性螺双二氢茚骨架的式1所示的消旋或旋光活性的7,7′-二甲氧基-1,1′-螺双二氢茚类化合物为起始原料,经过下述反应式:
其中:R1、R2如权利要求1所定义。
在有机溶剂、硼试剂和铱催化剂及含氮配体存在的条件下,具有式1所示的化合物在反应器中反应4~12小时制备得到式2a所示的化合物;在有机溶剂、溴化钠和双氧水存在条件下,式1所示的化合物在反应器中反应12~24小时制备得到式2b所示的化合物;式2a所示的化合物在钯催化剂下与芳基或烷基溴代物反应得到式3所示的化合物;式2b所示的化合物在钯催化剂下与芳基或烷基硼酸反应得到式3所示的化合物。
在有机溶剂、三溴化硼或二乙氨基乙硫醇钠存在的条件下,式3所示的化合物脱除甲基得到4所示的化合物;在有机溶剂存在条件下,式4所示的化合物与三氯氧磷反应得到磷酰氯,然后水解得到式5所示的化合物。
式5所示化合物与醋酸铑反应,交换掉醋酸根得到式I所示的化合物。
在上述合成方法中,所述的有机溶剂可为甲苯、四氢呋喃、环戊基甲基醚、二氯甲烷、N,N-二甲基甲酰胺、吡啶、氯苯中的一种或其中几种的混合溶剂。
4.根据权利要求1和2中所述的手性螺环磷酸双铑配合物的应用,其特征是用于催化卡宾对硅氢键的不对称插入反应。
5.根据权利要求4中所述的应用,其特征是在有机溶剂中,以权利要求1所述的具有通式I的化合物为手性催化剂,催化双芳基卡宾对硅氢键对映选择性插入,并获得手性有机硅化合物。
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CN114085385A (zh) * | 2021-12-02 | 2022-02-25 | 苏州金宏气体股份有限公司 | 一种除去储氢材料中杂质的改性金属有机框架的制备方法 |
CN115611716A (zh) * | 2022-10-26 | 2023-01-17 | 武汉大学 | 3,3’-二甲基取代的手性螺环二酚类化合物及其制备方法 |
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