CN1190397A - 作为手性配体的杂芳香二膦 - Google Patents
作为手性配体的杂芳香二膦 Download PDFInfo
- Publication number
- CN1190397A CN1190397A CN95194093A CN95194093A CN1190397A CN 1190397 A CN1190397 A CN 1190397A CN 95194093 A CN95194093 A CN 95194093A CN 95194093 A CN95194093 A CN 95194093A CN 1190397 A CN1190397 A CN 1190397A
- Authority
- CN
- China
- Prior art keywords
- phenyl
- chiral
- lian
- general formula
- linearity
- 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
- 239000003446 ligand Substances 0.000 title claims abstract description 9
- 125000001072 heteroaryl group Chemical group 0.000 title description 2
- 238000002360 preparation method Methods 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 26
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 13
- 150000003624 transition metals Chemical class 0.000 claims abstract description 13
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 114
- 230000002829 reductive effect Effects 0.000 claims description 48
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 35
- 239000001301 oxygen Substances 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 238000013507 mapping Methods 0.000 claims description 20
- -1 substituted-phenyl Chemical group 0.000 claims description 17
- 150000002240 furans Chemical class 0.000 claims description 15
- 239000003205 fragrance Substances 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 10
- 150000003233 pyrroles Chemical class 0.000 claims description 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 7
- 238000006317 isomerization reaction Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000003217 pyrazoles Chemical class 0.000 claims description 6
- 238000005516 engineering process Methods 0.000 claims description 5
- IAAQEGBHNXAHBF-UHFFFAOYSA-N 3-thiophen-3-ylthiophene Chemical compound S1C=CC(C2=CSC=C2)=C1 IAAQEGBHNXAHBF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 240000000233 Melia azedarach Species 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000000129 anionic group Chemical group 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 150000002790 naphthalenes Chemical class 0.000 claims description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 2
- 238000001640 fractional crystallisation Methods 0.000 claims description 2
- 238000005691 oxidative coupling reaction Methods 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- 238000006722 reduction reaction Methods 0.000 abstract description 20
- 230000008569 process Effects 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 62
- 239000002904 solvent Substances 0.000 description 58
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
- 229910052757 nitrogen Inorganic materials 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- 150000002475 indoles Chemical class 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 229930192474 thiophene Natural products 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
- 238000004821 distillation Methods 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 239000011259 mixed solution Substances 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 239000010948 rhodium Substances 0.000 description 11
- 229940074386 skatole Drugs 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- SCHRRICRQNJJKN-UHFFFAOYSA-N P.[O] Chemical compound P.[O] SCHRRICRQNJJKN-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 10
- 239000002184 metal Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 8
- 238000013019 agitation Methods 0.000 description 7
- 230000006837 decompression Effects 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910020366 ClO 4 Inorganic materials 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- OMSUIQOIVADKIM-UHFFFAOYSA-N ethyl 3-hydroxybutyrate Chemical compound CCOC(=O)CC(C)O OMSUIQOIVADKIM-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000004679 31P NMR spectroscopy Methods 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000012069 chiral reagent Substances 0.000 description 5
- 238000005194 fractionation Methods 0.000 description 5
- 229910052703 rhodium Inorganic materials 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229960001866 silicon dioxide Drugs 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 230000005526 G1 to G0 transition Effects 0.000 description 4
- 239000005792 Geraniol Substances 0.000 description 4
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229940113087 geraniol Drugs 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- WRGLZAJBHUOPFO-UHFFFAOYSA-N methyl 3-oxo-3-phenylpropanoate Chemical compound COC(=O)CC(=O)C1=CC=CC=C1 WRGLZAJBHUOPFO-UHFFFAOYSA-N 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 229910052707 ruthenium Inorganic materials 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VYXHVRARDIDEHS-QGTKBVGQSA-N (1z,5z)-cycloocta-1,5-diene Chemical compound C\1C\C=C/CC\C=C/1 VYXHVRARDIDEHS-QGTKBVGQSA-N 0.000 description 3
- NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 3
- PRPSHVVAZDXSJJ-UHFFFAOYSA-N 4,6-dimethyl-1-benzofuran-3-one Chemical compound CC1=CC(C)=CC2=C1C(=O)CO2 PRPSHVVAZDXSJJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000013375 chromatographic separation Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 125000004437 phosphorous atom Chemical group 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 230000000707 stereoselective effect Effects 0.000 description 3
- YSFLQVNTBBUKEA-UHFFFAOYSA-N 1-bromo-2,4-dimethylbenzene Chemical compound CC1=CC=C(Br)C(C)=C1 YSFLQVNTBBUKEA-UHFFFAOYSA-N 0.000 description 2
- UIERETOOQGIECD-ARJAWSKDSA-M 2-Methyl-2-butenoic acid Natural products C\C=C(\C)C([O-])=O UIERETOOQGIECD-ARJAWSKDSA-M 0.000 description 2
- ONPJWQSDZCGSQM-UHFFFAOYSA-N 2-phenylprop-2-enoic acid Chemical compound OC(=O)C(=C)C1=CC=CC=C1 ONPJWQSDZCGSQM-UHFFFAOYSA-N 0.000 description 2
- LPEKGGXMPWTOCB-UHFFFAOYSA-N 8beta-(2,3-epoxy-2-methylbutyryloxy)-14-acetoxytithifolin Natural products COC(=O)C(C)O LPEKGGXMPWTOCB-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- UIERETOOQGIECD-UHFFFAOYSA-N Angelic acid Natural products CC=C(C)C(O)=O UIERETOOQGIECD-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229910052693 Europium Inorganic materials 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- MIOPJNTWMNEORI-ZDFGOMNRSA-N [2,2,3,3,4,5,5-heptadeuterio-7-methyl-6-oxo-7-(trideuteriomethyl)-1-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C12(C(=O)C(C(C(C1([2H])[2H])([2H])[2H])(C2(C([2H])([2H])[2H])C)[2H])([2H])[2H])CS(=O)(=O)O MIOPJNTWMNEORI-ZDFGOMNRSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000002902 bimodal effect Effects 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- NQBWNECTZUOWID-QSYVVUFSSA-N cinnamyl cinnamate Chemical compound C=1C=CC=CC=1\C=C/C(=O)OC\C=C\C1=CC=CC=C1 NQBWNECTZUOWID-QSYVVUFSSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229960003280 cupric chloride Drugs 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 2
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- 229940057867 methyl lactate Drugs 0.000 description 2
- YLHXLHGIAMFFBU-UHFFFAOYSA-N methyl phenylglyoxalate Chemical class COC(=O)C(=O)C1=CC=CC=C1 YLHXLHGIAMFFBU-UHFFFAOYSA-N 0.000 description 2
- CWKLZLBVOJRSOM-UHFFFAOYSA-N methyl pyruvate Chemical compound COC(=O)C(C)=O CWKLZLBVOJRSOM-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000000711 polarimetry Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- UIERETOOQGIECD-ONEGZZNKSA-N tiglic acid Chemical compound C\C=C(/C)C(O)=O UIERETOOQGIECD-ONEGZZNKSA-N 0.000 description 2
- UAXOELSVPTZZQG-UHFFFAOYSA-N tiglic acid Natural products CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 2
- 239000005052 trichlorosilane Substances 0.000 description 2
- QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical compound COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
- GLZPCOQZEFWAFX-JXMROGBWSA-N (E)-Geraniol Chemical compound CC(C)=CCC\C(C)=C\CO GLZPCOQZEFWAFX-JXMROGBWSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- 229930007886 (R)-camphor Natural products 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- YPGCWEMNNLXISK-ZETCQYMHSA-N (S)-hydratropic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC=C1 YPGCWEMNNLXISK-ZETCQYMHSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- QPVRKFOKCKORDP-UHFFFAOYSA-N 1,3-dimethylcyclohexa-2,4-dien-1-ol Chemical compound CC1=CC(C)(O)CC=C1 QPVRKFOKCKORDP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- CXNFOKYCSXHBFJ-UHFFFAOYSA-N 2-(oxomethylidene)cyclopentane-1-carboxylic acid Chemical compound OC(=O)C1CCCC1=C=O CXNFOKYCSXHBFJ-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- SRWDQSRTOOMPMO-UHFFFAOYSA-N 3-bromo-1-benzothiophene Chemical compound C1=CC=C2C(Br)=CSC2=C1 SRWDQSRTOOMPMO-UHFFFAOYSA-N 0.000 description 1
- SXPOMOHAHKKGGA-UHFFFAOYSA-N 4-(2,3-dimethylbenzoyl)oxy-2,3-dihydroxy-4-oxobutanoic acid Chemical compound CC1=C(C(=CC=C1)C(=O)OC(=O)C(C(C(=O)O)O)O)C SXPOMOHAHKKGGA-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ITATYELQCJRCCK-UHFFFAOYSA-N Mandelic Acid, Methyl Ester Chemical compound COC(=O)C(O)C1=CC=CC=C1 ITATYELQCJRCCK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 108091006503 SLC26A1 Proteins 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- AOWPVIWVMWUSBD-RNFRBKRXSA-N [(3r)-3-hydroxybutyl] (3r)-3-hydroxybutanoate Chemical compound C[C@@H](O)CCOC(=O)C[C@@H](C)O AOWPVIWVMWUSBD-RNFRBKRXSA-N 0.000 description 1
- WHLQQRGHOPIIMQ-UHFFFAOYSA-N [2-(2-diphenylphosphanyl-6-methylphenyl)-3-methylphenyl]-diphenylphosphane Chemical compound CC=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=1C(C)=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 WHLQQRGHOPIIMQ-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N alpha-phenylpropionic acid Natural products OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- FWXAUDSWDBGCMN-ZEQRLZLVSA-N chiraphos Chemical compound C=1C=CC=CC=1P([C@@H](C)[C@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-ZEQRLZLVSA-N 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- SLLGVCUQYRMELA-UHFFFAOYSA-N chlorosilicon Chemical compound Cl[Si] SLLGVCUQYRMELA-UHFFFAOYSA-N 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- OMSUIQOIVADKIM-YFKPBYRVSA-N ethyl (3s)-3-hydroxybutanoate Chemical compound CCOC(=O)C[C@H](C)O OMSUIQOIVADKIM-YFKPBYRVSA-N 0.000 description 1
- OMSUIQOIVADKIM-RXMQYKEDSA-N ethyl (R)-3-hydroxybutanoate Chemical compound CCOC(=O)C[C@@H](C)O OMSUIQOIVADKIM-RXMQYKEDSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000005669 hydrocyanation reaction Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- ITATYELQCJRCCK-QMMMGPOBSA-N methyl (2s)-2-hydroxy-2-phenylacetate Chemical compound COC(=O)[C@@H](O)C1=CC=CC=C1 ITATYELQCJRCCK-QMMMGPOBSA-N 0.000 description 1
- LPEKGGXMPWTOCB-VKHMYHEASA-N methyl (S)-lactate Chemical compound COC(=O)[C@H](C)O LPEKGGXMPWTOCB-VKHMYHEASA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003579 shift reagent Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000001291 vacuum drying 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
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
- B01J31/1865—Phosphonites (RP(OR)2), their isomeric phosphinates (R2(RO)P=O) and RO-substitution derivatives thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
- B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- 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
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- 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
-
- 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
- C07F9/655—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
-
- 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
- C07F9/6553—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
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
- B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/50—Complexes comprising metals of Group V (VA or VB) as the central metal
- B01J2531/52—Antimony
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/822—Rhodium
-
- 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
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
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)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Pyridine Compounds (AREA)
- Catalysts (AREA)
- Liquid Crystal Substances (AREA)
Abstract
由芳香五元联杂环系统构成的适合作为手性配体的手性二膦,所说的二膦与过渡金属间的配合物及其作为手性催化剂在立体控制反应如非对映和对映选择还原反应中的应用。制备手性二膦和配合物的方法及其在作为手性催化剂在立体控制反应中的应用。
Description
本发明的目的是手性二膦、所述二膦与过渡金属间形成的配合物、以及它们作为手性催化剂在立体选择性(立体控制)反应中的应用,如象一般的非对映和对映选择性还原反应,或一般的不对称异构化反应。
本发明的另一目的是制备所说的手性二膦,和制备所说的手性配合物的方法以及它们在非对映和对映选择性反应中作为催化剂的应用方法。
本发明的再一个目的是立体选择性方法,特别是使用所说手性催化剂的一般非对映和对映选择性还原反应。
现有技术
已知立体选择反应,特别是象非对映或对映氢化反应这样的立体控制的还原反应,是非常重要的,并已被研究了很长时间;事实上,此类反应直接导致光学活性化合物的形成,而此类化合物以前只能以消旋体获得,需要对对映体进行随后的分离,以及与完成此分离有关的缺点是在进行分离过程中,有时发现具有极大的可能性使得不能得到纯的对映体;除此之外,在这种情况下,再一个缺点是存在非希望的对映体,必须将其加以回收或丢弃。
一般地,通过手性催化剂实现的立体控制还原反应允许获得光学活性的反应产物,也常具有好的对映体过量百分数。
例如,第一个不饱和化合物的对映选择氢化反应是通过使用附着在手性载体上的金属催化剂来完成的,而这可以追溯到30年代。以后,均相非对称氢化反应得以研究及阐述。通过由过渡金属和作为金属配体的手性二膦形成的配合物组成的特殊手性催化剂,实现了此反应。
文献报道了不同类型的手性膦,可作为配体并与过渡金属,如钌(Ru)、铑(Rh)、钯(Pd)、铱(Ir)和铂(Pt),形成手性配合物。特别是手性膦可以一个或两个立体生产性的磷原子为特点,在此情况,磷上有三个不同的取代基,例如DIPAMP,其中(R,R)对映体有如下通式:[KNOWLES W.S.等,J.Chem.Soc.Chem.Commun.10(1972);VINEYARD B.D.等,J.Am.Chem.Soc.99,5946(1977)];也有报道认为膦的手性是由于基于碳的立体中心的存在,例如已知为CHIRAPHOS的化合物,其(S,S)对映体有如下结构:[FRYZUK M.D.等,J.Am.Chem.Soc.99,6262(1977)];也有报道认为膦的手性是由于atropisomeric联芳基体系的存在,即围绕连接两个芳基的单键的转动被阻止;此种类型的二膦有BINAP,BIPHEMP或BICHEP,它们的(R)对映体有如下的通式:[NOYORI R.等,J.Am.Chem.Soc.102,7932(1980);SCHMID R.等,Helv.Chim.Acta71,897(1988);MIYASHITA A.等,Chem.Lett.1849(1989)]。
例如目前,用于立体控制还原反应,象可获得最好的二级手性醇之非对映和对映超量百分数的羰基非对映和对映选择性氢化的催化剂,是那些由过渡金属与atropisomery造成的手性二膦组成的配合物,特别是Ru和BINAP形成的配合物。
当然,主要的问题在于做为配体的手性二膦的合成。前面提到的实例中,手性膦的合成过程相当复杂,除涉及许多步骤之外,所获得的是一外消旋体,需要费力的拆分过程,收率低且费用很高。结果,通过手性二膦与过渡金属配合物的形成而得到的手性催化剂是非常昂贵的。
本发明的目的
本发明的一个目的是提供手性二膦,其通过特殊稳定的配价键的形成,适于做为过渡金属的配体。
本发明的另一个目的是提供一种手性二膦,以便与已知技术相比从合成的观点更容易得到。
本发明的再一个目的是提供一种制备适宜做为过渡金属配体的手性二膦的方法,其包括简单的步骤,成本低廉,并且是工业上能应用的。
本发明的进一步目的是提供一种新的手性催化剂,用于立体控制的合成反应。
本发明的另一个目的是提供一种手性催化剂,用于立体控制的合成反应,象具有高活性,以及高的位置、化学、非对映、对映选择性。
本发明的再一个目的是提供一种手性催化剂,用于立体控制的合成反应,象允许在温和反应条件操作,无论怎样都得到高的反应速率。
本发明的另一个目的是允许实现立体控制的反应,特别是还原反应或异构化反应,其中涉及手性催化剂的使用,以及导致高非对映体或对映体过量百分数的光学活性产物的生成。
发明的描述
这些以及仍存在的其它目的和在以下描述中将清晰解释的相关优点,是通过由芳香五元联杂环系统构成的手性二膦来实现的。
更为特别的是,所说的由芳香五元联杂环系统构成的手性二膦具有下列通式:其中:R2选自氢,苯基,芳基,C1-C10的线性、支链、环状烷基,COOR3,其中R3是C1-C10的线性、支链、环状烷基;Y选自苯基,取代苯基,芳基,取代芳基,C3-C10的线性、支链、环状烷基;R1选自苯基,取代苯基,芳基,取代芳基,C1-C10的线性、支链、环状烷基,OR5,其中R5是C1-C10的线性、支链、环状烷基,或;根据下面的通式,所说系统的每一个五元杂环芳香环缩合到取代的或未取代的苯或萘环上:其中n从0到6,R2也可以等于零,R4选自氢,C1-C10的线性、支链、环状、取代或未取代的烷基。
芳香五元联杂环系统选自:1,1′-联吡咯,2,2′-联吡咯,3,3′-联吡咯3,3′-联噻吩3,3′-联呋喃1,1′-联咪唑以及相应的苯并的(IIA)(IIB),(VA)(VB),4,4′-联吡唑,5,5′-联吡唑1,1′-联-1,3,4-三氮唑4,4′-联异噁唑4,4′-联异噻唑5,5′-联咪唑3,3′-联苯并噻吩3,3′-联苯并呋喃2,2′-联吲哚1,1′-联苯并咪唑。
根据本发明,具有以下通式手性二膦:证明是特别有利的。
而且根据本发明,具有如下结构式的手性二膦:证明是特别有利的。
而且根据本发明,具有如下结构式的手性二膦:证明是特别有利的。
特别地,所说的二膦(IA)(IB),(IIA)(IIB),(VA)(VB)的手性是由于五元芳香联杂环系统的存在,该系统是C2对称atropisomeric系统,即特征为沿连接两个杂环系统的键存在高的旋转障碍[Eliel;Stereochemistry of Carbon Compounds,Int.Stud.Edition McGraw Hill-Tokyo 1962-p.156 foll.]。
而且,所说的根据本发明的二膦特征是,杂环系统,当其富电子时,增加磷原子的电子效力。由于有这些特征,根据本发明的二膦被有利地用做在与过渡金属形成配合物的制备中的手性配体,其中配体的电子效力正好有助于与金属间的共价键,此电子效力是通过杂环系统给予磷原子的;此配合物反过来在立体控制的合成,特别是非对映和对映选择的还原反应,如氢化反应中被用做手性催化剂。
而且根据本发明,所说的手性二膦是根据包括简单步骤的方法制备的。
根据本发明以及单独地经由实施例,示意性地阐述制备具有总式(IA)(IB)手性二膦的一般方法。所说的方法包括以下步骤:-通过相应五元杂环阴离子的氧化偶合,合成五元芳香联杂环系统;-形成联杂环系统的联阴离子;-所说的联阴离子与P(Y)2Cl或PO(Y)2Cl反应,其中Y选自苯基,取代苯基,芳基,取代芳基,C3-C10的线性、支链、环状烷基,获得外消旋的二膦(IA)+(IB)或外消旋的二膦氧;-根据已知的技术用氧化反应把所说的外消旋二膦(IA)+(IB)转化为相应的外消旋二膦氧;-所说的外消旋二膦氧与酸性手性拆分试剂反应,获得非对映加合物;-用分级结晶分离所说的非对映加合物;-碱性处理所说的两个分离的非对映加合物的每一个,产生相应的对映体纯的二膦氧;-用已知的还原剂,如硅烷类,还原所说的对映体纯的二膦氧,产生所说的对映体纯的手性二膦(IA)和(IB)。
显然,芳香联杂环系统也可以根据其它对本部分的技术人员来说已知的技术来制备。除此之外,遇到含氮产生的杂环时,所说的联杂环系统的联阴离子的形成也可以在氮原子上发生。
更特别地,总是根据本发明,通过利用手性方法的柱层析,如固定相,洗脱系统等,有助于所说的外消旋二膦(IA)+(IB)被直接地拆分。
而所说的手性拆分试剂优选自,例如,二苯甲酰酒石酸,二甲苯甲酰酒石酸,樟脑磺酸等。
如已上述的,根据本发明的手性二膦被用做过渡金属配位的配体,特别是VIII族金属,如Ru,Rh,Pd,Ir,以形成手性配合物,作为立体控制的反应的催化剂。
根据本发明,手性配体与金属间形成的配合物,优选地通过手性二膦与所选金属的配合物之间的交换反应来获得,其中金属与配体间的键要比将在金属与二膦间形成的键更不稳定;这样,二膦将取代那个与金属配合的配体,构成优选的配合键。特别地在上面的交换反应中,金属用来与配体,例如象1,5-顺,顺-环辛二烯,降冰片二烯,(乙烯)2,三芳基月弟,苄腈等配位。
特别地,所选金属与配体组成的配合物溶于合适的溶剂中,然后加入以固体状态或溶于合适的溶剂中的手性二膦;反应的进行以及后来手性配合物的形成,由可能的颜色变化检查来跟踪,同样也可用光谱的方法,如31P-NMR和GC来跟踪。在反应末了,除去溶剂,形成的手性配合物可以其存在的形式使用,或根据已知的技术经进一步的纯化。
优选用于手性配合物制备的溶剂是,例如,氯化生成的溶剂,醇,芳香烃(甲苯),醚类,二甲基甲酰胺。上述手性配合物优选地在它们被用做立体控制反应的催化剂时制备。
总是根据本发明,由手性二膦与过渡金属形成的配合物组成的手性催化剂,与在已知技术中应用的手性催化剂相比证明是更具选择性;事实上,与已知的传统配体相比,基于本发明的二膦配体的几何形状可以决定不同的键长和键角,因而使用所说的手性催化剂的立体选择反应提供了有利条件,如惊人的反应速度,温和的反应条件,例如它涉及压力和温度条件以及使用的催化剂量,也有使用低生态影响的溶剂的可能性。
除此之外,所说的手性催化剂具有高的化学,对映以及非对映选择性,并且被有利地用于完成立体控制的反应,特别是非对映和对映选择性还原反应,例如,链烯(-C=C-)的还原,酮羰基(-C=O)的还原,亚氨基(-C=N-)的还原,烯胺基(-N-C=C)的还原,得到具有高非对映体和对映体过量百分数的光学活性化合物。
根据本发明,所说的手性催化剂被用于完成羰基化反应,氢氰化反应和双键异构化反应。通过本发明的非限制性实施例的方法,一些手性二膦(IIIR)(IIIS),(IVR)(IVS),(VIR)(VIS),(VIIR)(VIIS),(VIIIR)(VIIIS)的制备,一些由所说的二膦分别与金属Ru和Rh形成的手性配合物的制备,以及根据本发明所说的配合物做为手性催化剂的应用描述如下;例如,它们在3-羰基丁酸乙酯,2-羰基环戊烷羧酸甲酯,α-乙酰胺基肉桂酸及其它物质还原中的应用。
实施例1
手性二膦(III R)和(III S)的制备a)4,4’,6,6’-四甲基-3,3’-二苯并[b]噻吩的合成
溶解于11ml无水乙醚的4.1g 3-溴-4,6-二甲基-苯并噻吩,在搅拌下滴入到并冷却至-70℃的含1.6M BuLi(12ml)的11ml无水乙醚溶液中。让反应混合物静置30分钟,然后加入2.7g CuCl2并保持搅拌反应混合物6小时,在0℃冷却,然后加入17ml 2MHCl,让反应液静置过夜。然后把形成的有机盐除去,有机相用乙醚萃取,Na2SO4干燥,减压除去溶剂。得到的残留物经硅胶柱层析,用己烷作洗脱剂,收集中间组分,减压除溶剂,这样获得0.70g 4,4’,6,6’-四甲基-3,3’-二苯并[b]噻吩。
1H-NMR(300MHz)(CDCl3)(ppm):1.9(6H,s,2CH3),2.4(6H,s,2CH3),6.9(2H,s,5,5′位芳香氢),7.2(2H,s,噻吩),7.5(2H,s,7,7′位芳香氢)。
质谱(EI):(M+)322b)合成2,2′-双(二苯基膦)-4,4’,6,6’-四甲基-3,3’-二苯并[b]噻吩
向含0.35g 4,4’,6,6’-四甲基-3,3’二苯并[b]噻吩和0.39g TMEDA的20ml无水THF溶液中,在惰性环境和-50℃温度下,滴入1.1ml 1.6M BuLi。半小时后,温度升到0℃并滴入0.5ml二苯基氯膦。反应混合物反应12小时,然后减压除去溶剂并用水处理。有机相用乙醚萃取,Na2SO4干燥,减压除去溶剂。异丙基醚处理得到的残留物,获得0.4g 2,2′-双(二苯基膦)-4,4’,6,6’-四甲基-3,3’-二苯并[b]噻吩.。
1H-NMR(300MHz)(CDCl3)(ppm):1.6(6H,s,2CH3),2.4(6H,s,2CH3),6.7(2H,s,5,5′位芳香氢),6.9-7.5(22H,m,7,7′位芳香氢+4C6H5)。
质谱(EI):(M+)690
31P-NMR(200MHz)(CDCl3)(ppm):-24.98(2P,s)c)外消旋二膦到二膦氧的氧化
在0℃,2ml H2O2滴加入到溶于80ml CH2Cl2的由b)得到的1.4g二膦溶液中。温度保持0℃ 1小时和25℃ 1小时,然后加入10ml水并分离出有机相,除水后减压除去溶剂。
1.5g反应混合物进行层析,用AcOEt/CH2Cl2/Et3N 3/7/0.1混合液(V/V)洗脱。收集尾部组分,得到1.4g外消旋二膦氧,收率96%。
1H-NMR(300MHz)(CDCl3)(ppm):1.5(6H,s,2CH3),2.4(6H,s,2CH3),6.7(2H,s,5,5′位芳香氢),7.0-7.8(22H,m,7,7′位芳香氢+4C6H5)。
质谱(EI):(M+)772
31P-NMR(200MHz)(CDCl3)(ppm):20.36(2P=O,s)。d)拆分:二膦氧(-)
1.2g由c)获得的外消旋二膦氧和0.36g(-)-O,O′-二苯甲酰-L-酒石酸(DBTA)热溶解于58ml包含AcOEt/CHCl3 50∶8(v/v)的混合液。24小时后,过滤得到500mg二膦氧(-)与DBTA(-)形成的加合物,熔点=218-220℃,[α]D 25=-143°(c=0.55EtOH)。e)对d)加合物的处理
用9.6ml 0.75N的NaOH处理500mg加合物,此混合物用2×9.6ml CHCl3萃取两次。合并如此获得的有机相,用6.4ml 0.75N的NaOH,6.4ml水洗并用Na2SO4干燥。
过滤出混合物,溶剂减压蒸除,得到320mg手性二膦氧(-)。如此得到的二膦氧具有[α]D 25=-226°(c=0.45溶剂苯)。f)拆分:二膦氧(+)
由d)方法得到的滤液减压除去溶剂,获得的1g残留物用18ml 0.75N的NaOH处理,并用18ml CHCl3萃取两次。收集的有机相用12ml 0.75N的NaOH和12ml水洗,然后用Na2SO4干燥并减压除去溶剂。得到0.60g杂有二膦氧(-)的二膦氧(+)。如此得到的混合物与0.312g DBTA(+)混合并一同热溶解于29ml包含AcOEt/CHCl3 25/4(v/v)的混合液。24小时后,过滤混合物,得到0.4g由二膦氧(+)与DBTA(+)加合物组成的固体,熔点=216-220℃,[α]D 25=+147°(c=0.55 EtOH)。
如e)所述的处理加合物并获得二膦氧(+),特征为[α]D 25=+229°(c=0.56溶剂苯)。g)还原
将0.4g在f)所述的二膦氧(+)溶于6ml二甲苯,然后在惰性条件下,加入0.59ml Et3N和0.42ml HSiCl3。反应混合物在100℃加热1小时,120℃加热1小时和140℃加热6小时。剩余的二甲苯和三氯硅烷在减压下除去,残留物用水处理并用20ml CH2Cl2萃取。然后干燥反应混合物,减压除去溶剂,如此获得的粗产物在惰性环境下用闪式层析分离,用己烷/CH2Cl2(v/v)混合液做洗脱液。得到350mg二膦(+),特征为[α]D 25=+215°(c=0.4,溶剂苯)。
在e)所述获得的二膦氧(-)通过类似的方法被还原为二膦(-),得到类似的收率;二膦(-)的特征为[α]D 25=-222°(c=0.4,溶剂苯)。
实施例2
手性二膦(IV R)和(IV S)的制备a)2,2’,5,5’-四甲基-3,3’-二噻吩的合成
溶解于5ml乙醚的5.46g 3-溴-2,5-二甲基噻吩,滴入到处于氮气环境和-70℃温度的18ml BuLi 1.5M溶液中。30分钟后,剧烈搅拌下加入4.13g CuCl2并保持搅拌反应混合物3小时。温度升至0℃,然后加入6N HCl溶液至氯化铜溶解。水相用120ml乙醚萃取,乙醚相用15ml水洗,然后用12ml碳酸钠饱和溶液洗,再用12ml水洗。溶液用Na2SO4干燥,减压除去溶剂;这样得到的残留物经硅胶柱层析,用己烷作洗脱剂,收集中间组分,获得1.73g 2,2’,5,5’-四甲基-3,3’-二噻吩,收率55%。
1H-NMR(300MHz)(CDCl3)(ppm):6.52(2H,宽单峰,4,4′位芳香氢),2.41(6H,s,2CH3),2.27(6H,s,2CH3)。b)4,4′-二溴-2,2’,5,5’-四甲基-3,3’-二噻吩的合成
溶解在四氯化碳的0.5ml溴滴入到0℃含有1.97g 2,2’,5,5’-四甲基-3,3’-二噻吩的12ml四氯化碳溶液中;温度升高,15分钟后,保持温度在40℃,滴入溶于同样体积四氯化碳的同样量的溴。30分钟后,加入100ml二氯甲烷,混合液分别用20ml碳酸钠饱和溶液,20ml水洗,然后有机相用硫酸钠干燥。减压除去溶剂得到3.60g油状残留物,所说的残留物经硅胶柱层析,用己烷洗脱。收集初组分,减压蒸除溶剂,获得1.47g 4,4′-二溴-2,2’,5,5’-四甲基-3,3’-二噻吩,收率44%,特征为熔点m.p.=93-95℃。
1H-NMR(300MHz)(CDCl3)(ppm):2.40(6H,s,2CH3),2.15(6H,s,2CH3)。c)4,4′-双二苯基膦氧-2,2’,5,5’-四甲基-3,3’-二噻吩的制备
在-15℃,2分钟的时间内,向溶于25ml无水THF的1.37g 4,4′-二溴-2,2’,5,5’-四甲基-3,3’-二噻吩溶液中,滴入5ml 1.6M的BuLi溶液。20分钟后,在0℃滴入1.46ml二苯基氯膦,让反应混合物静置1小时30分钟。然后加入100ml乙醚,混合液用10ml水洗,有机相用硫酸钠脱水。溶剂减压除去,得到2.70g残留物。通过溶解在100mlCH2Cl2并在0℃温度滴加3.6ml 30%过氧化氢,把残留物全部氧化成二膦氧。2小时后,加入15ml水,分离出有机相并用Na2SO4干燥。减压除去溶剂,得到残留物。此残留物经硅胶柱层析,用包含CH2Cl2/AcOEt/Et3N 7/3/0.2(v/v/v)的混合液洗脱。收集尾部组分,减压除去溶剂,获得的油状物用乙醚处理,得到0.190g 4,4′-双二苯基膦氧-2,2’,5,5’-四甲基-3,3’-二噻吩。
1H-NMR(300MHz)(CDCl3)(ppm):7.60(20H,m,芳香氢),1.95(6H,d,2,2′位CH3),1.65(6H,s,5,5′位CH3)。
根据类似于实施例1 d)的步骤利用在THF中的DBTA,可以通过结晶非对映体的盐来拆分此产物。0.7g的二膦氧和0.42g(-)-二苯甲酰酒石酸(DBTA)混合物热溶解在20ml THF中。12小时后,过滤得到0.2g(-)-二膦氧与(-)-DBTA形成的加合物,熔点为180℃,[α]D 25=-44°(c=0.5,EtOH)。
根据普通方法处理加合物,得到560mg膦氧。
掺杂(-)-膦氧的0.56g(+)-膦氧与0.34g(+)-DBTA热溶于40ml THF。12小时后,回收0.185g(+)-二膦氧与(+)-DBTA形成的加合物,熔点为178℃,[α]D 25=+39.5°(c=0.55,EtOH)。d)4,4′-双二苯基膦氧-2,2’,5,5’-四甲基-3,3’-二噻吩的制备
在氩气环境下,向溶于5ml二甲苯的0.053g 4,4′-双二苯基膦氧-2,2’,5,5’-四甲基-3,3’-二噻吩溶液中,加入0.14ml三乙胺和0.10ml三氯硅烷。反应混合物在100℃加热1小时,120℃加热1小时和140℃加热6小时。用4ml水处理反应混合物,并用20ml CH2Cl2萃取。有机相用无水硫酸钠干燥,用机械泵蒸发掉溶剂,获得4,4′-双二苯基膦-2,2’,5,5’-四甲基-3,3’-二噻吩。
所得到的外消旋二膦的拆分通过HPLC来完成,用DAICEL CHIRALCEL OD(25cm×4mm)柱,己烷/异丙醇做洗脱液,流速=0.7ml/min。
实施例3
配合物{Ru[化合物(IIIR)(+)]Cl2}的制备
带有侧插口,底部圆锥型和涂有特氟龙的搅拌子的试管被反复抽出和压入氩气;该操作至少重复5次。以如下次序向尾试管中加入16.0mg光学纯的手性二膦(IIIR)(+)(2.3×10-2mmols),根据文献报道的方法制备的5.6mg[RuCl2(C6H6)]2(1.15×10-2mmols),以及4ml在惰性环境下新蒸出的二甲基甲酰胺,并氩气脱气15分钟。红棕色悬浮物搅拌下在100℃加热15分钟;该悬液快速转变为澄清的橙黄色溶液。该溶液冷至50℃并蒸发干燥,残留物机械真空1小时,然后压入氩气。这样得到的钌配合物不用进一步纯化,用于酮酯的对映选择性还原。
实施例4
配合物{Rh[1,5-环辛二烯][化合物(III S)(-)]ClO4}的制备
带有侧插口,底部圆锥型和涂有特氟龙的搅拌子的试管被反复抽出和压入氩气;该操作至少重复5次。11.0mg光学纯的手性二膦(III S)(-)(1.59×10-2mmols)加入试管中并溶于在惰性气体中蒸出的CH2Cl2中,使用前氩气脱气15分钟。过量的[Rh(1,5-COD)2]ClO4被称重并加入到尾试管,闪光并压入氩气;加入准确计算体积的CH2Cl2,得到黄色溶液。用注射器抽取准确含有1.59×10-2mmol的体积,加入到二膦III溶液中。溶液快速转变为橙黄色;该溶液搅拌30分钟,蒸发至剩{Rh[1,5-COD][化合物(IIIS)(-)]ClO4}的橙黄色固体。这样得到的铑配合物不用进一步纯化,用于链烯的对映选择性还原。
实施例5
3-羰基-丁酸乙酯还原为(R)-(-)-3-羟基丁酸乙酯
带有玻璃衬里,磁力搅拌器和加热器的75ml不锈钢高压釜几次压入氢至4.90MPa和抽空(此循环至少重复5次),并在70℃恒温。2.993g(23.0mmoles)3-羰基-丁酸乙酯和20ml预先氩气脱气15分钟的甲醇加入到根据实施例3所述的方式制备的催化剂中。此溶液用注射器转移至高压釜内,该高压釜加压到9.81MPa。120分钟后,高压釜冷却,打开,溶剂蒸除至只剩棕色油状残留物。样品通过GC(柱PEG 20M,炉温100℃,FID 200℃,注射器200℃)和1H-NMR谱检测;结果显示底物定量的转变,3-羟基丁酸乙酯的选择性等于95%;副产物是3-二甲氧基丁酸乙酯。残留物真空蒸馏,收集在17mmHg的75-80℃的馏分。得到的样品是化学纯的氢化产物。
3-羟基丁酸乙酯:1H-NMR(200MHz)(CDCl3)(ppm):4.2(3H,重叠的四重峰和多重峰),2.4(2H,双峰),1.2(6H,重叠的三重峰和双重峰)。
用旋光及三[3-(+)樟脑三氟甲基羟基亚甲基]铕做位移手性试剂的1H-NMR谱测定立体还原作用。比旋光度是[α]D 20=-41.5(c=1,CHCl3),相当于99%光学纯(O.P.),为R对映体[文献报道(S)-(+)对映体:[α]D 20=+42±1(c=1,CHCl3);A.FISCHLI,Modern synthetic methods Vol.2,269,1980,R.Scheffold Publishing House,Salle+Sauerlander]。用位移手性试剂通过1H-NMR谱测定对映体过量百分数。在外消旋还原产物上加入位移试剂造成在1.2ppm处的三重峰分离为分别在1.40和1.55ppm处的两个三重峰。同样的手性试剂加入到对映选择性还原产物中造成三重峰移至1.4ppm处,而无论如何未显示出在1.55ppm处三重峰的存在。这一结果使对映体过量百分数超过99%得到证实。
实施例6
2-羰基环己酸甲酯还原为(R,R)-(-)-2-羟基环己酸甲酯
设备的准备步骤与实施例5的相同。将在20ml脱气甲醇中的3.270g(23.0mmoles)2-羰基环己酸甲酯加入到如实施例3制备的催化剂中,高压釜在70℃恒温并加压到9.81MPa。120分钟后,高压釜冷却,打开,溶剂蒸除至只剩棕色油状残留物。样品GC检查(柱:PEG 20M,炉温160℃,FID 200℃,注射器200℃);转变证明是定量的,反/顺比例等于30,所以非对映体过量百分数等于94%。残留物真空蒸馏,收集在17mmHg的100-110℃的馏分。得到的样品证明是化学纯的氢化产物。
2-羟基环己酸甲酯:1H-NMR(200MHz)(CDCl3)(ppm):4.35(1H,多重峰),3.71(3H,单峰),2.65(1H,多重峰),2.4-1.5(6H,多重峰)。用1H-NMR谱和三[(+)樟脑3-八氟甲基羟基亚甲基]铕位移手性试剂测定立体还原作用。在外消旋还原产物上加入位移反应剂造成在4.40ppm处的四重峰分离为分别在5.2和5.85ppm处的两个四重峰。同样的手性试剂加入到立体选择性还原产物中造成四重峰移至5.85ppm处,而无论如何未显示出在5.2ppm处四重峰的存在。这一结果使对映体过量百分数超过99%得到证实。
实施例7
α-乙酰胺肉桂酸的还原
带有磁力搅拌的100ml玻璃高压釜被几次在98.1MPa压入氢和抽空(此循环至少重复5次),并在30℃恒温;溶于40ml预先氩气脱气15分钟的甲醇中的500mgα-乙酰胺肉桂酸(2.06 mmoles)加入到根据实施例4所述的方式制备的催化剂中;这样得到的溶液用注射器移入到高压釜中。高压釜加压至0.3MPa。反应过程用压力计压力下降来跟踪。180分钟后,氢吸收作用停止,打开高压釜,溶液的样品用1H-NMR谱分析。底物乙酰基在2.1ppm的信号的消失以及N-乙酰基苯基丙氨酸在1.90ppm的甲基的出现表明100%转化。溶液通过短的硅胶柱过滤以除去铑配合物。旋光测定立体选择作用。残留物样品(0.211),溶解于25ml甲醇给出α=+0.193°,对应的[α]D 25=+22.9°。
实施例8
手性二膦(VIR)和(VIS)的制备a)N-(苯磺酰基)-3-甲基吲哚的制备
50%氢化钠(1.1g)加入到溶于无水DMF(50ml)的3-甲基吲哚(4g)溶液中,保持温度低于30℃。搅拌15分钟,然后小心地滴入溶在无水DMF(20ml)的苯磺酰氯(4.7ml)。在25℃搅拌2小时。然后加入甲醇(5ml)以分解可能存在的微量BuLi;减压除去溶剂,加入水(20ml)并用二氯甲烷充分萃取。有机相用硫酸钠除水,溶剂减压除去。残留物(9.5)在二氯甲烷/己烷1∶1中研磨,得到N-(苯磺酰基)-3-甲基吲哚(2g)(m.p.116-120℃)。母液层析分离以回收更多的产物,用二氯甲烷/己烷1∶1洗脱。从中间组分回收N-(苯磺酰基)-3-甲基吲哚(7g),减压除去溶剂。总反应收率:85%。
1H-NMR详细数据:7.99(1H,双重峰,J=8Hz,7位H);7.86(1H,双重峰,J=8Hz,苯环邻位上H);7.85(1H,双重峰,J=8Hz,苯环邻位上H);7.38(6H,多重峰,芳香);7.31(1H,单峰,2位H);2.25(3H,单峰,3位CH3)。b)N,N′-双(苯磺酰基)-3,3′-二甲基-2,2′-双吲哚的制备
在保持于-30℃由N-苯磺酰基-3-甲基吲哚(30g)和TMEDA(100ml)和无水THF(10ml)组成的溶液中,滴入1.6M(61ml)的BuLi。在同样温度搅拌30分钟,加入无水氯化铜(13g)并让其在室温静置1小时。溶剂减压除去,然后加入水(5ml),用二氯甲烷充分萃取。有机相用无水硫酸钠干燥并减压除去溶剂。
在异丙醇中热研磨残留物,获得N,N′-双(苯磺酰基)-3,3′-二甲基-2,2′-双吲哚(6g)(m.p.234℃)。
1H-NMR详细数据:8.35(2H,双重峰,J=8Hz,7和7′位H);7.48(10H,多重峰,芳香H);7.3(6H,多重峰,芳香);1.62(6H,单峰,3和3′位CH3)。
质谱(EI):(M+)540。
滤液用异丙醇冷研磨,回收未反应的N-苯磺酰基-3-甲基吲哚(8g)。母液硅胶层析分离,用二氯甲烷/己烷1∶1洗脱。头流出组分是N-苯磺酰基-3-甲基吲哚(7g)。收集尾部组分并除去溶剂,产生N,N′-双(苯磺酰基)-3,3′-二甲基-2,2′-双吲哚(4.5g)。
c)制备2-[2-(3-甲基-3-羟基)-δ1-二氢吲哚基]-3-甲基吲哚
N,N′-双(苯磺酰基)-3,3′-二甲基-2,2′-双吲哚(10g),氢氧化钾(8.3g),二氧六环(80ml)在乙醇(300ml)中的悬浮液回流5小时,然后除去溶剂。反应混合物用水处理,并用二氯甲烷充分地萃取。有机相用硫酸钠干燥,溶剂减压除去。所得到的混合物在二氯甲烷中充气搅拌24小时,过滤回收起始产物。此固体是2-[2-(3-甲基-3-羟基)-δ1-二氢吲哚基]-3-甲基吲哚(2g)(m.p.94℃)。1H-NMR详细数据:9(1H,单峰,NH);7.52(1H,双重峰,J=7.9Hz,4′位H),7.29(1H,双重峰,J=5.6Hz,7位H);7.14(1H,三重峰,J=7.9Hz,6′位H),7(5H,多重峰,芳香氢);1.52(3H,单峰,靠近OH的CH3)。
母液层析分离,先用二氯甲烷及随后用二氯甲烷/乙酸乙酯10∶0.1洗脱。从尾部组分回收2-[2-(3-甲基-3-羟基)-δ1-二氢吲哚基]-3-甲基吲哚(0.7g),减压除去溶剂。d)制备3,3′-二甲基-2,2′-二吲哚
2-[2-(3-甲基-3-羟基)-δ1-二氢吲哚基]-3-甲基吲哚(2.5g)热溶解在已充氮气除去任何残留氧的乙醇中。滴加溶于最少量水(10ml)的硼氢化钠(0.51g)并在25℃保持搅拌2小时。滴入10%盐酸溶液到pH 6并继续搅拌12小时。残留物在氮气下过滤,以定量的产率产生3,3′-二甲基-2,2′-二吲哚(m.p.146-149℃)。1H-NMR详细数据:8(2H,宽单峰,NH);7.63(2H,双重峰,J=8Hz,4和4′位H),7.39(2H,双重峰,J=8Hz,7和7′位H);7.25(2H,三重峰,J=8Hz,5和5′H),7.18(2H,三重峰,J=8Hz,5和5′H);2.40(6H,单峰,3和3′位的CH3)。e)N,N′-双(二苯基膦)-3,3′-二甲基-2,2′-双吲哚的制备
1.6M(1.1ml)BuLi滴入到溶在-20℃并充分脱气的无水THF(85ml)中的3,3′-二甲基-2,2′-二吲哚(0.24g)溶液,2分钟后,再滴入溶于无水THF(5ml)的二苯基氯化膦(0.4g)。
保持搅拌16小时,减压除去溶剂并加入水(20ml)。用二氯甲烷充分萃取,硫酸钠除水并减压除去溶剂。残留物硅胶层析,用己烷/二氯甲烷8∶2洗脱;从头流出物中回收的组分在异丙醇中研磨,产生N,N′-双(二苯基膦)-3,3′-二甲基-2,2′-双吲哚(m.p.>230℃),收率95%。
1H-NMR详细数据:7.59(2H,双峰,J=8Hz,,4和4′位H);7.3(14H,多重峰,芳香氢);7.1(611,多重峰,芳香氢),6.85(2H,三重峰,J=5Hz,6和6′H);6.7(2H,双重峰,J=8Hz,,7和7′位H),2.05(6H,单峰,3和3′位的CH3)。31P-NMR:37(1P,单峰)
质谱(EI):(M+)628。f)N,N′-双(二苯基氧膦基)-3,3′-二甲基-2,2′-双吲哚的制备
在-30℃,35%H2O2(0.16ml)滴加入到溶于CH2Cl2(5m1)的N,N′-双(二苯基膦基)-3,3′-二甲基-2,2′-双吲哚(0.1g)溶液中。温度保持-30℃ 2小时。加入水并分离出有机相,该有机相除水后减压除去溶剂,得到外消旋N,N′-双(二苯基氧膦基)-3,3′-二甲基-2,2′-双吲哚(0.1g)。
1H-NMR详细数据:1.8(6H,s,3和3′位的2CH3),7.3(28H,m,芳香氢)。g)拆分1,1′-双(二苯基氧膦基)-3,3′-二甲基-2,2′-双吲哚
0.28g二膦氧混合物和0.21g d-10-樟脑磺酸热溶解在9ml由甲苯/CH2Cl2 8∶1(v/v)组成的混合液中。60小时后,得到78mg二膦氧与d-10-樟脑磺酸形成的加合物,熔点=125-1127℃,[α]D=+34°(c=1.56。MeOH)。
二膦氧的还原用如实施例1 g)描述的同样方法来实现。
实施例9
手性二膦(VIIR)和(VIIS)的制备a)制备3,3′-二苯并[b]噻吩
溶于无水THF(40ml)的3-溴-苯并[b]噻吩(15.1g),搅拌下被滴入到处于-70℃的n-BuLi 1.6M(48ml)溶液中。让其反应15分钟,加入CuCl2(13g),继续搅拌1小时。升温到0℃并加入HCl 2M(98ml)。所形成的有机盐过滤除去,溶剂减压蒸馏并向残留物中加入水。CH2Cl2萃取,硫酸钠于燥,减压蒸馏出溶剂。残留物硅胶层析,用己烷作洗脱剂,收集中间组分得到3,3′-二苯并[b]噻吩(56%收率)。
1H-NMR:7.38(4H,多重峰,5,6,5′,6′位H);7.55(2H,单峰,2位H),7.72-7.98(4H,多重峰,4,7,4′,7′位H)。b)制备2,2′-双(二苯基膦)-3,3′-二苯并[b]噻吩
在氮气环境及搅拌下,1.6M(8.4ml)n-BuLi滴入到处于-50℃,溶于无水THF(40ml)的3,3′-二苯并[b]噻吩(1.7g)和四甲基二胺(1.15ml)溶液中,温度升至0℃。滴入Ph2PCl(2.4ml)并在室温静置。减压蒸馏出溶剂,向残留物中加入水并用CH2Cl2萃取。有机相用硫酸钠干燥,减压蒸馏出溶剂。残留物用石油醚研磨产生2,2′-双(二苯基膦)-3,3′-二苯并[b]噻吩(3.12g,m.p.=177℃)(99%产率)。c)制备2,2′-双(二苯基氧膦基)-3,3′-二苯并[b]噻吩
在0℃,35%H2O2(5.5ml)滴加入到溶于CH2Cl2(100ml)的2,2′-双(二苯基膦)-3,3′-二苯并[b]噻吩溶液中。温度保持0℃ 1小时和25℃ 1小时。加入水并分离出有机相,该有机相除水后减压除去溶剂。残留物硅胶层析(洗脱液AcOEt/CH2Cl2/Et3N3/7/0.1),收集尾部组分,得到外消旋2,2′-双(二苯基氧膦基)-3,3′-二苯并[b]噻吩(3.65g,m.p.=286℃)(收率68.5%)。d)制备(+)2,2′-双(二苯基氧膦基)-3,3′-二苯并[b]噻吩和(-)2,2′-双(二苯基氧膦基)-3,3′-二苯并[b]噻吩
用AcOEt(90ml)和CHCl3(43ml)溶液热溶解(±)2,2′-双(二苯基氧膦基)-3,3′-二苯并[b]噻吩(2.15g)及(-)-0,0′-二苯甲酰基-L-酒石酸(DBTA)(1.2g)的混合物。24小时后,过滤回收(+)膦氧和(-)-DBTA形成的加合物(0.54g),m.p.=185-190℃,[α]D 25=+100.6°(c=0.50,EtOH)。此加合物在硅胶柱上过滤,用CH2Cl2/AcOEt/TEA=7/3/0.1的混合液作洗脱剂,回收(+)膦氧(0.212g),[α]D 25=+325°(c=0.48,苯),m.p.=206℃。
(+)膦氧拆分的母液减压除去溶剂,得到的残留物在硅胶柱上过滤,用CH2Cl2/AcOEt/TEA=7/3/0.1的混合液作洗脱剂。回收的夹杂有(+)膦氧的(-)膦氧(6g)用(+)-DBTA(3.4g)处理。此混合物用AcOEt(255ml)和CHCl3(147ml)溶液热溶解。24小时后,过滤回收(-)膦氧和(+)-DBTA形成的加合物(4g),[α]D 25=-97.4°(c=0.47,EtOH),m.p.=190℃。此加合物在硅胶柱上过滤,用CH2Cl2/AcOEt/TEA=7/3/0.1的混合液作洗脱剂,回收(-)膦氧(2.7g),[α]D 25=-329°(c=0.5,苯),m.p.=206℃。e)制备(+)2,2′-双(二苯基膦)-3,3′-二苯并[b]噻吩和(-)2,2′-双(二苯基膦)-3,3′-二苯并[b]噻吩
二膦氧的还原用如实施例1,g)描述的同样方法来实现。二膦氧(+)特征为[α]D 25=+119°(c=0.551,IMF),而二膦氧(-)特征为[α]D 25=-119°(c=0.51,DMF)。产物熔点为117℃。
实施例10
制备(R)和(S)N,N′-双(二苯基膦)-1,1′-二苯并咪唑a)制备1,1′-二苯并咪唑
200ml高锰酸钾(1.6g)溶液滴入到2,2′-diphormyl-1,1′-二苯并咪唑(3.00g)在水(200ml),苯(70ml)以及1.12g碳酸钠中的悬浮液中。混合物搅拌48小时。加入亚硫酸氢钠至二氧化锰消失,然后用10%盐酸把溶液调到酸性pH,有机相用二氯甲烷萃取,硫酸钠干燥,减压除去溶剂,产生的残留物用异丙基醚除去表层,得到1.5g m.p.188℃的产物(61.7%收率)。
1H-NMR:7.02(2H,双重峰,4和4′位的H),7.3-7.5(4H,多重峰,5和5′,6和6′位的H),7.92(2H,双重峰,7和7′位的H),8.17(2H,单峰,2和2′位的H)。
M.W.(质谱):294b)制备N,N′-双(二苯基膦)-1,1′-二苯并咪唑
在-60℃和惰性环境中,9.4ml 1.6M BuLi滴入到1,1′-二苯并咪唑(1.5g)在无水THF(70ml)和2.25ml TMEDA的溶液中。温度升到0℃,滴入2.78ml二苯基氯化膦。反应混合物搅拌2小时,温度升到20℃并加入甲醇。此混合物减压除去溶剂,残留物用水和二氯甲烷处理。有机相用硫酸钠处理并减压除去溶剂,产生残留物,用乙酸乙酯结晶(3.00g用450ml),得到m.p.=227℃的产物(78%产率)。
1H-NMR:6.3(2H,双重峰,7和7′位的H),6.93(2H,三重峰,6和6′位H),7.11-7.39(20H,多重峰,在对位和间位芳香H及5和5′位H),7.51-7.59(2H,多重峰,邻位芳香H),7.88(2H,双重峰,4和4′位芳香H)。
31P NMR谱在-28.3ppm处显示一个单峰。
M.W.(质谱):分子峰缺失,525(M+-C6H5)。c)二膦的拆分
外消旋体二膦的拆分以如实施例2,d)同样的方法用HPLC完成。
实施例11
制备[Ru{化合物(III S)}(-)]Cl2 1
制备方法与实施例3的类似,但采用37.0mg的[(III S)(-)]和13.0mg的[RuCl2(C6H5)]2。
实施例12
苯甲酰乙酸甲酯还原成(R)-(+)-3-苯基-3-羟基-丙酸甲酯
带有玻璃衬里,磁力搅拌和加热的75ml不锈钢高压釜被几次压入氢至4.90MPa并抽空(此循环至少重复5次),并在25℃恒温。溶在50ml预先氩气脱气15分钟的甲醇的9.25g(52mmoles)苯甲酰乙酸甲酯加入到根据实施例11所述的方式制备的催化剂中。
此溶液用注射器转移至加压到10.2MPa的高压釜内。100小时后,高压釜降压,溶剂蒸除至剩固体。通过1H-NMR谱测定的转化为92%,。
反应产物用制备柱层析(SiO2,CH2Cl2)纯化。对映体纯度用旋光测定。产品样本比旋光度为[α]D 25=+15.3°(c=4.6,EtOH),对应于90%的光谱纯度,为(R)-(+)异构体。([α]D 25=+17.22°(c=4.6,EtOH);[A.McKezie和G.Martin,J.Chem.Soc.,1913,103,112])。
实施例13
苯酰甲酸甲酯还原为(S)-(+)-扁桃酸甲酯
重复实施例12的步骤,将苯甲酰乙酸甲酯替换为苯酰甲酸甲酯(8.5g,51.8mmoles)。
100小时后,打开高压釜,溶剂蒸除。通过柱层析(SiO2,己烷/CH2Cl2 7/3 v/v)得到化学纯扁桃酸甲酯。通过带有手性固定相(DAICEL,Chiralcel OD;流速0.5ml/min,己烷/异丙醇90∶10)的HPLC检测对映体纯度,结果等于90%,为对映体(s)-(+)。
实施例14
丙酮酸甲酯还原为(S)-(-)-乳酸甲酯
重复实施例12的步骤,将苯甲酰乙酸甲酯替换为丙酮酸甲酯(3.13mg,30.74mmoles)。
100小时后转化为100%(1H-NMR),蒸除溶剂并蒸出乳酸甲酯(50℃,17mmHg)。乳酸甲酯转化为相应的(+)MTPA酯后,根据常规方法,通过HPLC分析检测对映体过量百分数,88%为对映体(S)。
实施例15
制备[Ru{化合物(VII S)}(-)]Cl2 1
制备同实施例11,但使用10.6mg[(VII S)(-)]和3.7mg[RuCl2(C6H5)]2。
实施例16
3-羰基丁酸乙酯还原为(S)(+)3-羟基丁酸乙酯
重复实施例5的相同的方法,差别在于称重1.95g 3-羰基-丁酸乙酯并溶于MeOH/H2O19/1(v/v),并用实施例15的催化剂。反应结束,所得3-羟基丁酸乙酯为91%,而3-二甲氧基丁酸乙酯为9%。有利于对映体(S)的立体还原作用>99%。
实施例17
制备[Ru(化合物III S)(-)(CH3COO)2]
[Ru(化合物III S)(-)Cl2]配合物如实施例11那样制备,但使用47mg[(III S)(-)]和17mg[RuCl2(C6H5)]2。22.7mg乙酸银和7ml无水甲苯被加入到如此获得的残留物中。悬液搅拌1小时,随后在短微晶纤维素柱上过滤,用更多的甲苯洗脱所有的催化剂。甲苯溶液包含[Ru(化合物III S)(-)(CH3COO)2],保持在氩气环境下,未进一步纯化被用做催化还原。
实施例18
香叶醇还原成(R)-(+)-β-香茅醇
含有0.015mmoles由实施例17制备的催化剂的甲苯溶液蒸干,889mg的香叶醇和10ml的甲醇被加入到残留物中。生成的溶液转移到钢制高压釜中,高压釜在10.2MPa加压,在于25℃恒温的浴器中保持搅拌85小时。
结束时,打开高压釜并蒸发掉溶剂。转化结果是100%(1H-NMR)。
残留物bulb-to-bulb蒸馏(110℃,10mmHg)。(R)-(+)-β-香茅醇的比旋光度结果是[α]D 25=+4.44(净值),产生的光谱纯等于83%([α]D 25=+5.33,净值)。
实施例19
惕各酸还原成(S)-(+)-2-二甲基丁酸
重复如实施例18的相同方法,差别在于使用600mg的惕各酸代替香叶醇。
高压釜在10.2MPa加压,置于25℃恒温的浴器中并且磁力搅拌85小时。
经通常的处理后,得到100%转化(1H-NMR)。产物bulb-to-bulb蒸馏(78℃,15mmHg)。对映体纯度由HPLC在手性固定相(DAICEL,Chiralcel OD;流速0.7ml/min,己烷/异丙醇95/5)上,通过酸与苯胺缩合得到的酰胺测定,结果等于90%。
实施例20
阿托酸还原成(S)-(+)-2-苯基丙酸
重复如实施例18的相同方法,差别在于使用742mg的阿托酸代替香叶醇。高压釜在10.2MPa加压,置于25℃恒温的浴器中并且磁力搅拌90小时。
经通常的处理后,得到100%转化(1H-NMR)。产物bulb-to-bulb蒸馏(115℃,1mmHg)。对映体纯度由HPLC在手性固定相(DAICEL,Chiralcel OD;流速0.5ml/min,己烷/异丙醇90/10)上,通过酸与苯胺缩合得到的酰胺测定,结果等于90%,为对映体(S)-(+)。
实施例21
制备[Ru[(化合物III S)(-)]2]ClO4
1.1ml 0.0424M的AgClO4无水甲苯溶液,在氩气环境下加入到含有11.6ml[Rh(1,5-COD)Cl]n的尾管内。室温搅拌1小时后,混合物通过一短硅藻土柱过滤。向如此获得的淡黄色溶液中加入32.5mg(化合物III S)(-)。溶液搅拌3小时,然后再加入32.5mg(化合物III S)(-)。此混合物在氢环境下保持再搅拌16小时,然后减压蒸出溶剂,桔红色残留物用石油醚洗三次并真空干燥过夜。如此形成的配合物[Rh[(化合物IIIS)(-)]2ClO4未进一步纯化,用于N,N-二乙基-香叶胺异构化。配合物的NMR、质谱以及元素分析与前面提到的结构一致。
实施例22
N,N-二乙基-香叶胺的异构化。(R)(+)-香茅醛的制备
如前面实施例21所述方法制备的15mg[Ru[(化合物III S)(-)]2]ClO4的无水THF溶液和0.99g N,N-二乙基-香叶胺的12mlTHF溶液,用注射器转移至预先充氩气的高压釜中。高压釜磁力搅拌下置于110℃恒温的浴器中。9小时后,取出溶液样品(1ml),用9ml二异丙基醚稀释并在0℃用冰乙酸/水(v/v)1∶4溶液5ml处理10′。在20℃再过10′后,分离有机相,用饱和NaHCO3溶液洗,硫酸钠干燥,GC分析。转化结果约是80%。进一步反应10小时后,溶液浓缩至于并如上所述处理,用20ml二异丙基醚及10ml 1∶4的冰乙酸/水(v/v)。最后,有机相浓缩,残留物蒸馏获得(R)(+)-香茅醛,比旋光度是[α]D 25=+15.2(净值),对应于约92%的光谱纯。
实施例23
2,2′-双(二苯基氧膦基)-4,4′-四甲基-3,3′-[b]呋喃的制备a)2-(3,5-二甲基苯氧基)乙酸乙酯
3,5-二甲基苯酚(0.082moles)的甲醇(30ml)溶液滴入到甲醇钠(0.098moles)的甲醇溶液中并保持搅拌30分钟。混合物减压除去溶剂。产生3,5-二甲基苯酚钠。溶解在DMF(20ml)中的2-溴乙酸乙酯(0.098moles),被滴入到由盐溶解在无水DMF(150ml)中所得到的溶液中。混合物室温搅拌4小时,然后减压除去溶剂,用水处理并用二氯甲烷萃取。有机相分离,除水(NaSO4),减压除去溶剂后产生22.7g粗2-(3,5-二甲基苯氧基)乙酸乙酯,未进一步纯化(定量的产率)就被用于随后的反应。
分析和谱数据:1H-NMR:δH(300MHz,CDCl3)1.28(3H,三重峰,CH2CH3),2.25(6H,单峰,3,5-Me),4.25(2H,四重峰,CH2CH3),4.5(2H,单峰,CH2CO),6.5(2H,单峰,2,6-H),6.6(1H,单峰,4-H)。b)2-(3,5-二甲基苯氧基)乙酸
KOH(0.11moles)加入到2-(3,5-二甲基苯氧基)乙酸乙酯(0.11moles)的乙醇(159ml)溶液中,加热1小时至出沉淀物。过滤所形成的钾盐并溶解在水中。向溶液中加入20%盐酸到pH酸性。过滤得到2-(3,5-二甲基苯氧基)乙酸(80%收率)。
分析和谱数据:1H-NMR:δH(80MHz,CDCl3)2.30(6H,单峰,3,5位甲基),4.65(2H,单峰,CH2CO),6.55(2H,单峰,2,6位氢),2.65(1H,单峰,4-H)。c)4,6-二甲基-3-苯并呋喃酮
聚磷酸和2-(3,5-二甲基苯氧基)乙酸的混合物在50℃加热8小时。混合物倾入冰中,用氨处理到pH7。混合物用二氯甲烷萃取,有机相用碳酸氢钠溶液处理,除水(Na2SO4)并减压除去溶剂,得到4,6-二甲基-3-苯并呋喃酮(40%转化,100%产率)。
分析和谱数据:m.p.55-60℃1H-NMR:δH(80MHz,CDCl3)2.25(3H,单峰,Me),2.45(3H,单峰,Me),4.40(2H,单峰,CH2),6.50(1H,单峰,芳香氢),6.60(1H,单峰,芳香氢)。d)4,6-二甲基-3-溴苯并呋喃
4,6-二甲基-3-苯并呋喃酮(0.09moles)慢慢加入到预先加热到100℃的三溴化磷(30ml)中。混合物小心地用冰处理,二氯甲烷萃取。有机相除水(Na2SO4)并减压除去溶剂,得到4,6-二甲基-3-溴苯并呋喃(60%产率)。
分析和谱数据:1H-NMR:δH(80MHz,CDCl3)2.40(3H,单峰,Me),2.70(3H,单峰,Me),6.85(1H,单峰,5-H),7.15(1H,单峰,7-H),7.50(1H,单峰,2-H)。e)4,4′,6,6′-四甲基-3,3′-二苯并[b]呋喃
溶于无水THF(20ml)的4,6-二甲基-3-溴苯并呋喃(0.012moles),搅拌下滴入到温度-105℃的n-BuLi 1.6M(9ml)的己烷溶液中。混合物反应20分钟,加入CuCl2(0.014moles),搅拌混合物3小时。在0℃加入HCl 2M(20ml)。溶剂减压蒸馏,向残留物中加入水。用CH2Cl2萃取后,混合物除水(Na2SO4)并且减压蒸馏出溶剂。残留物在硅胶柱上层析,用己烷作洗脱剂,收集尾部组分,得到4,4′,6,6′-四甲基-3,3′-二苯并[b]呋喃(30%产率)。
分析和谱数据:m.p.98-100℃1H-NMR:δH(80MHz,CDCl3)2.10(6H,单峰,2Me),2.45(6H,单峰,2Me),6.85(2H,单峰,5,5′-H),7.18(2H,单峰,7,7′-H),7.50(2H,单峰,2,2′-H)。质谱:M+=290f)2,2′-双(二苯基膦基)-4,4′,6,6′-四甲基-3,3′-[b]呋喃
在氮气环境和搅拌下,1.6M n-BuLi(2ml)滴入到4,4′,6,6′-四甲基-3,3′-二苯并[b]呋喃(0.0014mmoles)和四甲基二胺的-50℃无水THF(10ml)溶液中,然后温度升至25℃。滴入Ph2PCl(0.63ml)。减压蒸馏出溶剂,残留物中加入水并用CH2Cl2萃取有机相。有机相除水(Na2SO4)并减压除去溶剂。残留物用石油醚研磨,产生2,2′-双(二苯基膦基)-4,4′,6,6′-四甲基-3,3′-[b]呋喃(60%产率)。
分析和谱数据:1H-NMR:δH(300MHz,CDCl3)1.90(6H,单峰,2Me),2.40(6H,单峰,2Me),6.75(2H,单峰,5,5′-H),7.80(22H,多重峰,芳香氢)。31P δH(200MHz,CDCl3)-32.15质谱:M+=658。g)2,2′-双(二苯基氧膦基)-4,4′,6,6′-四甲基-3,3′-[b]呋喃
35% H2O2(5.5ml)滴加入到2,2′-双(二苯基膦基)-4,4′,6,6′-四甲基-3,3′-[b]呋喃(0.45g)的0℃ CH2Cl2(30ml)溶液中。温度保持在0℃ 15分钟,在25℃ 1小时。加入水,分离出有机相,有机相除水后减压除去溶剂。残留物硅胶柱层析(洗脱剂:AcOEt/CH2Cl2=2/8),收集尾部组分,得到外消旋2,2′-双(二苯基氧膦基)-4,4′,6,6′-四甲基-3,3′-[b]呋喃(90%收率)。
分析和谱数据:1H-NMR:δH(300MHz,CDCl3)1.80(6H,单峰,2Me),2.20(6H,单峰,2Me),6.35(2H,单峰,5,5′-H),7.00-7.80(22H,多重峰,芳香氢)。31P=+16.9按照实施例2 d)同样的方法,用HPLC手性柱完成拆分。
Claims (15)
1.手性二膦,其特征在于其是由芳香五元联杂环系统构成的。
2.如权利要求1的手性二膦,其特征在于由按照下列通式的芳香五元联杂环系统构成:其中:R2选自氢,苯基,芳基,C1-C10的线性、支链、环状烷基,COOR3,其中R3是C1-C10的线性、支链、环状烷基;Y选自苯基,取代苯基,芳香基,取代芳香基,C3-C10的线性、支链、环状烷基;R1选自苯基,取代苯基,芳香基,取代芳香基,C1-C10的线性、支链、环状烷基,OR5,其中R5是C1-C10的线性、支链、环状烷基,或根据下面的通式,所说系统的每一个五元杂环芳香环缩合到取代的或未取代的苯或萘环上:或根据下面的通式:其中R4选自氢,C1-C10的线性、支链、环状,取代的或未取代的烷基,n的范围从0-6,R2可以等于零。
3.如权利要求1的手性二膦,其特征在于所说的芳香五元联杂环系统选自:1,1′-联吡咯,2,2′-联吡咯,3,3′-联吡咯3,3′-联噻吩3,3′-联呋喃1,1′-联咪唑以及相应的苯并缩合物(IIA)(IIB),(VA)(VB),5,5′-联咪唑4,4′-联异噻唑4,4′-联异噁唑4,4′-联吡唑,5,5′-联吡唑1,1′-联-1,3,4-三氮唑3,3′-联苯并噻吩3,3′-联苯并呋喃2,2′-联吲哚1,1′-联苯并咪唑。
4.如权利要求2的手性二膦,其特征在于所说的R2等于零,Y是苯基,五元芳环是噻吩并根据分子式(IIA),(IIB)缩合到二取代的苯环上,其中R4是甲基,n等于2,通式如下:
5.如权利要求2的手性二膦,其特征在于所说的R2是甲基,Y是苯基,R1是甲基,所说的芳香五元联杂环系统是3,3′-联噻吩,通式如下:
6.权利要求2的手性二膦的制备方法,其特征在于它包含以下步骤:-通过相应五元杂环阴离子的氧化偶合,合成五元芳香联杂环系统;-形成联杂环系统的联阴离子;-所说的联阴离子与P(Y)2Cl或PO(Y)2Cl反应,其中Y选自苯基,取代苯基,芳基,取代芳基,C3-C10的线性、支链、环状烷基,获得外消旋的二膦(IA)+(IB)或外消旋的二膦氧;-根据已知的技术用氧化反应把所说的外消旋二膦(IA)+(IB)转化为相应的外消旋二膦氧;-所说的外消旋二膦氧与酸性手性拆分试剂反应,获得两个非对映加合物;-用分级结晶分离所说的非对映加合物;-碱性处理所说的两个分离的非对映加合物的每一个,产生相应的对映体纯的二膦氧;-用已知的还原剂,如硅烷类,还原所说的对映体纯的二膦氧,产生所说的对映体纯的手性二膦(IA)和(IB)。
7.如权利要求6的手性二膦的制备方法,其特征在于所说对映体二膦(IA)和(IB)用手性方法直接在柱层析上拆分。
8.权利要求1所说的手性二膦用做制备与过渡金属成为配合物的手性配体的应用。
9.立体控制合成的手性催化剂,其特征在于它包含过渡金属与由芳香五元联杂环系统组成的手性二膦之间形成的配合物。
10.如权利要求9的手性催化剂,其特征在于所说的手性二膦由具有以下通式的芳香五元联杂环系统构成:其中:R2选自氢,苯基,芳基,C1-C10的线性、支链、环状烷基,COOR3,其中R3是C1-C10的线性、支链、环状烷基;Y选自苯基,取代苯基,芳香基,取代芳香基,C3-C10的线性、支链、环状烷基;R1选自苯基,取代苯基,芳香基,取代芳香基,C1-C10的线性、支链、环状烷基,OR5,其中R5是C1-C10的线性、支链、环状烷基;或根据下面的通式,所说系统的每一个五元杂环芳香环缩合到取代的或未取代的苯环上:或根据下面的通式:其中R4选自氢,C1-C10的线性、支链、环状,取代的或未取代的烷基,n的范围从0-6,R2可以等于零,并且芳香五元联杂环系统选自:1,1′-联吡咯,2,2′-联吡咯,3,3′-联吡咯3,3′-联噻吩3,3′-联呋喃1,1′-联二咪唑以及相应的苯并缩合物(IIA)(IIB),(VA)(VB),5,5′-联咪唑4,4′-联异噻唑4,4′-联异噁唑4,4′-联吡唑,5,5′-联吡唑1,1′-联-1,3,4-三氮唑3,3′-联苯并噻吩3,3′-联苯并呋喃2,2′-联吲哚1,1′-联苯并咪唑。
11.权利要求10的手性催化剂在实现立体控制还原作用中的应用。
14.权利要求10的手性催化剂在实现立体控制异构化反应中的应用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI94A001438 | 1994-07-12 | ||
ITMI941438A IT1270082B (it) | 1994-07-12 | 1994-07-12 | Difosfine eteroaromatiche come leganti chirali, complessi tra dette difosfine e metalli di transizione ed impiego di detti complessi come catalizzatori chirali |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1190397A true CN1190397A (zh) | 1998-08-12 |
Family
ID=11369253
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN95194093A Pending CN1190397A (zh) | 1994-07-12 | 1995-07-07 | 作为手性配体的杂芳香二膦 |
Country Status (16)
Country | Link |
---|---|
US (5) | US5907045A (zh) |
EP (1) | EP0770085B1 (zh) |
JP (1) | JP3330611B2 (zh) |
KR (1) | KR100384411B1 (zh) |
CN (1) | CN1190397A (zh) |
AT (1) | ATE184878T1 (zh) |
AU (1) | AU685660B2 (zh) |
CA (1) | CA2193889C (zh) |
CZ (1) | CZ293465B6 (zh) |
DE (1) | DE69512415T2 (zh) |
DK (1) | DK0770085T3 (zh) |
ES (1) | ES2136896T3 (zh) |
GR (1) | GR3031443T3 (zh) |
HU (1) | HU221381B1 (zh) |
IT (1) | IT1270082B (zh) |
WO (1) | WO1996001831A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101148456B (zh) * | 2007-10-12 | 2011-07-27 | 北京大学 | 一种有机磷酸催化剂及其制备方法和应用 |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1286497B1 (it) * | 1996-11-20 | 1998-07-15 | Italfarmaco Sud Spa | Difosfine di tipo misto eteroariliche-ariliche come leganti chirali, relativi complessi con metalli di transizione e impiego di detti |
DE19652350A1 (de) * | 1996-12-17 | 1998-06-18 | Studiengesellschaft Kohle Mbh | Neue Katalysatoren aus Übergangsmetallverbindungen und 4,5-Diphosphinoacridin-Liganden |
JP3148136B2 (ja) * | 1996-12-26 | 2001-03-19 | 高砂香料工業株式会社 | 新規なキラルジホスフィン化合物、その製造中間体、該ジホス フィン化合物を配位子とする遷移金属錯体並びに該錯体を含む 不斉水素化触媒 |
US6162929A (en) * | 1997-12-23 | 2000-12-19 | Hoffmann-La Roche Inc. | Process for the manufacture of bisphosphine oxide and bisphosphonate compounds |
IT1299068B1 (it) * | 1998-04-10 | 2000-02-07 | Chemi Spa | Legandi fosforati chirali e loro complessi organometallici, utili come catalizzatori in sintesi stereoselettive |
FR2778915B1 (fr) * | 1998-05-20 | 2000-06-30 | Rhone Poulenc Fibres | Nouvelles furylphosphines et complexes organometalliques les comprenant |
IT1303757B1 (it) * | 1998-11-16 | 2001-02-23 | Sigma Tau Ind Farmaceuti | Processo industriale per la produzione di l-carnitina. |
DE19918420A1 (de) * | 1999-04-23 | 2000-10-26 | Aventis Res & Tech Gmbh & Co | Bidentate Organophosphorliganden und ihre Verwendung |
ATE324943T1 (de) | 1999-09-20 | 2006-06-15 | Penn State Res Found | Chirale phosphine, deren komplexe mit übergangsmetallen und deren verwendung in asymmetrischen synthesereaktionen |
DE10036516A1 (de) | 2000-07-27 | 2002-02-07 | Asta Medica Ag | Verfahren zur Herstellung von enantiomerenreinen 6,8-Dihydroxyoctansäureestern durch assymetrische katalytische Hydrierung |
DE10100708A1 (de) * | 2001-01-10 | 2002-07-11 | Oxeno Olefinchemie Gmbh | Neue N-Phenylpyrrolbisphosphanverbindungen und deren Metallkomplexe |
EP1383777B1 (de) * | 2001-03-29 | 2005-11-16 | Basf Aktiengesellschaft | Liganden für pnicogenchelatkomplexe mit einem metall der viii. nebengruppe und verwendung der komplexe als katalysatoren für hydroformylierung, carbonylierung, hydrocyanierung oder hydrierung |
CA2458430A1 (en) | 2001-10-05 | 2003-04-17 | Solvias Ag | Ligands for asymmetric reactions |
DE10242636A1 (de) * | 2002-09-13 | 2004-03-18 | Basf Ag | Verfahren zur Herstellung von Dialdehyden und/oder ethylenisch ungesättigten Monoaldehyden durch Hydroformylierung ethylenisch ungesättigter Verbindungen |
DK1720852T3 (da) | 2004-02-19 | 2012-10-22 | Lonza Ag | Fremgangsmåde til fremstilling af enantiomerrene 1-substituerede 3-aminoalkoholer |
EP1595888A1 (en) * | 2004-05-11 | 2005-11-16 | Degussa AG | Cycloolefin phosphine ligands and their use in catalysis |
CA2572845A1 (en) * | 2004-07-08 | 2006-02-16 | Merck & Co., Inc. | Formation of tetra-substituted enamides and stereoselective reduction thereof |
CN101175565B (zh) | 2005-04-08 | 2011-11-09 | 帝斯曼知识产权资产管理有限公司 | 内酯的制造 |
WO2006108636A1 (en) | 2005-04-15 | 2006-10-19 | Dsm Ip Assets B.V. | Manufacture of thiolactones |
US8455661B2 (en) * | 2007-02-18 | 2013-06-04 | University Of Florida Research Foundation, Inc. | Catalysts containing N-heterocyclic carbenes for enantioselective synthesis |
SG172217A1 (en) | 2008-12-16 | 2011-07-28 | Hoffmann La Roche | Process for the preparation of pyrollidine-3-carboxylic acids |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3966595A (en) * | 1972-07-20 | 1976-06-29 | E. I. Du Pont De Nemours And Company | Method of making group VIII metal complex compounds |
DE3403194A1 (de) * | 1984-01-31 | 1985-08-01 | Degussa Ag, 6000 Frankfurt | Optisch aktive 3,4-bis-(diphenylphosphino)-pyrrolidine, diese als chirale liganden enthaltende rhodiumkomplexe und deren verwendung |
US4755611A (en) * | 1985-04-16 | 1988-07-05 | Smithkline Beckman Corporation | Certain bio-(bi-2-thienyl or 2-furyl phosphino) lower alkanes having anti-tumor properties |
US4716230A (en) * | 1985-04-16 | 1987-12-29 | Smithkline Beckman Corporation | Certain bis(di-2 or 4-pyridyl-phosphino) alkanes #10 having anti-tumor properties |
JP2816555B2 (ja) * | 1988-03-07 | 1998-10-27 | 富士薬品工業株式会社 | 新規なホスフイノピロリジン化合物およびそれを用いる不斉合成法 |
GB9002491D0 (en) * | 1990-02-05 | 1990-04-04 | Shell Int Research | Carbonylation catalyst system |
EP0530336B1 (de) * | 1991-03-15 | 1996-03-06 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Chirale phosphine |
ES2116435T3 (es) * | 1992-01-31 | 1998-07-16 | Hoffmann La Roche | Ligandos difosfinicos. |
DE4330730A1 (de) * | 1993-09-10 | 1995-03-16 | Bayer Ag | Neue Bisphosphine für asymmetrische Hydrierkatalysatoren |
-
1994
- 1994-07-12 IT ITMI941438A patent/IT1270082B/it active IP Right Grant
-
1995
- 1995-07-07 KR KR1019970700159A patent/KR100384411B1/ko not_active IP Right Cessation
- 1995-07-07 CN CN95194093A patent/CN1190397A/zh active Pending
- 1995-07-07 CZ CZ199783A patent/CZ293465B6/cs not_active IP Right Cessation
- 1995-07-07 WO PCT/EP1995/002647 patent/WO1996001831A1/en active IP Right Grant
- 1995-07-07 EP EP95943147A patent/EP0770085B1/en not_active Expired - Lifetime
- 1995-07-07 US US08/765,479 patent/US5907045A/en not_active Expired - Fee Related
- 1995-07-07 AT AT95943147T patent/ATE184878T1/de not_active IP Right Cessation
- 1995-07-07 JP JP50411796A patent/JP3330611B2/ja not_active Expired - Fee Related
- 1995-07-07 ES ES95943147T patent/ES2136896T3/es not_active Expired - Lifetime
- 1995-07-07 DK DK95943147T patent/DK0770085T3/da active
- 1995-07-07 DE DE69512415T patent/DE69512415T2/de not_active Expired - Fee Related
- 1995-07-07 CA CA002193889A patent/CA2193889C/en not_active Expired - Fee Related
- 1995-07-07 AU AU30764/95A patent/AU685660B2/en not_active Ceased
- 1995-07-07 HU HU9700054A patent/HU221381B1/hu not_active IP Right Cessation
-
1999
- 1999-04-05 US US09/286,582 patent/US6133191A/en not_active Expired - Fee Related
- 1999-04-05 US US09/286,583 patent/US6297387B1/en not_active Expired - Fee Related
- 1999-04-27 US US09/300,531 patent/US6077958A/en not_active Expired - Fee Related
- 1999-10-07 GR GR990402532T patent/GR3031443T3/el unknown
-
2001
- 2001-08-24 US US09/938,354 patent/US6586357B1/en not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101148456B (zh) * | 2007-10-12 | 2011-07-27 | 北京大学 | 一种有机磷酸催化剂及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
DE69512415T2 (de) | 2000-01-05 |
DK0770085T3 (da) | 1999-12-20 |
US6586357B1 (en) | 2003-07-01 |
JPH10502387A (ja) | 1998-03-03 |
EP0770085B1 (en) | 1999-09-22 |
ITMI941438A0 (it) | 1994-07-12 |
HU221381B1 (en) | 2002-09-28 |
IT1270082B (it) | 1997-04-28 |
CZ293465B6 (cs) | 2004-05-12 |
ATE184878T1 (de) | 1999-10-15 |
HUT75997A (en) | 1997-06-30 |
CZ8397A3 (en) | 1997-06-11 |
CA2193889A1 (en) | 1996-01-25 |
AU3076495A (en) | 1996-02-09 |
AU685660B2 (en) | 1998-01-22 |
ITMI941438A1 (it) | 1996-01-12 |
US6133191A (en) | 2000-10-17 |
CA2193889C (en) | 2002-09-10 |
DE69512415D1 (de) | 1999-10-28 |
US5907045A (en) | 1999-05-25 |
ES2136896T3 (es) | 1999-12-01 |
JP3330611B2 (ja) | 2002-09-30 |
GR3031443T3 (en) | 2000-01-31 |
EP0770085A1 (en) | 1997-05-02 |
KR100384411B1 (ko) | 2003-08-21 |
WO1996001831A1 (en) | 1996-01-25 |
US6297387B1 (en) | 2001-10-02 |
US6077958A (en) | 2000-06-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1190397A (zh) | 作为手性配体的杂芳香二膦 | |
CN102177170B (zh) | 具有三齿配体的新型羰基钌配合物、其制备方法和用途 | |
Ohkuma et al. | Practical enantioselective hydrogenation of aromatic ketones | |
CN1291996C (zh) | 作为复分解反应(予)催化剂的钌络合物 | |
CN1610688A (zh) | 邻位取代的手性膦和三价膦酸酯及其在不对称催化反应中的用途 | |
CN1087298C (zh) | 双亚磷酸酯化合物及其制造方法和使用它的醛化方法 | |
CN1238361C (zh) | 螺环双膦配体 | |
CN1373741A (zh) | 改进的金属配体络合物催化方法 | |
JPH10182678A (ja) | 新規なキラルジホスフィン化合物、その製造中間体、該ジホス フィン化合物を配位子とする遷移金属錯体並びに該錯体を含む 不斉水素化触媒 | |
CN1950385A (zh) | 用于均相、对映选择性氢化催化剂的二茂铁基配体 | |
Kadyrov et al. | Efficient enantioselective synthesis of optically active diols by asymmetric hydrogenation with modular chiral metal catalysts | |
JP2004504371A (ja) | ルテニウム錯体および不斉水素化におけるその使用 | |
JP5454756B2 (ja) | ジホスフィン化合物、その遷移金属錯体およびその遷移金属錯体を含む触媒並びにホスフィンオキシド化合物及びジホスフィンオキシド化合物 | |
CN101058532A (zh) | 羟基的邻位具有手性中心的手性伯醇和仲醇的制备方法及其应用 | |
JP2003535869A (ja) | 不斉触媒用キラル配位子 | |
JP2002003441A (ja) | 光学活性トリメチル乳酸およびそのエステル類の製造方法 | |
CN1225095A (zh) | 由含环状手性膦配位体的过渡金属配合物催化的不对称合成 | |
JP2008538585A (ja) | 不斉ヒドロホルミル化プロセス | |
CN1281460A (zh) | 含刚性手性配体的不对称合成用催化剂 | |
EP2774908B1 (en) | Method for preventing decrease in optical purity | |
JP5011262B2 (ja) | ホスフィン化合物 | |
CN116063347A (zh) | 一类手性苯环骨架的膦-1,2-二苯基乙二胺配体及其制备方法和应用 | |
JP2012031119A (ja) | 軸不斉イソキノリン誘導体及びその製造方法並びに不斉合成方法 | |
Shi et al. | Axially Dissymmetric Chiral (R)‐N, W‐Bis (2‐hydroxy‐3, 5‐ditert‐butyl‐arylmethyl)‐1, 1′‐binaphthalene‐2, 2′‐diamine as Chiral Ligands in the Reaction of Diethylzinc to Aldehydes | |
Yan et al. | Hydroformylation of olefins catalyzed by chiral phosphite-Rh (I) complexes |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
AD01 | Patent right deemed abandoned | ||
C20 | Patent right or utility model deemed to be abandoned or is abandoned |