CN101120010B - 基于茂金属的磷手性膦 - Google Patents
基于茂金属的磷手性膦 Download PDFInfo
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- CN101120010B CN101120010B CN200680004909.8A CN200680004909A CN101120010B CN 101120010 B CN101120010 B CN 101120010B CN 200680004909 A CN200680004909 A CN 200680004909A CN 101120010 B CN101120010 B CN 101120010B
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- phosphorus
- metallocene
- ferrocene
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- 229910052698 phosphorus Inorganic materials 0.000 title abstract description 32
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title description 24
- 239000011574 phosphorus Substances 0.000 title description 24
- 150000003003 phosphines Chemical class 0.000 title description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052751 metal Inorganic materials 0.000 claims abstract description 6
- 239000002184 metal Substances 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- 229910052723 transition metal Inorganic materials 0.000 claims description 4
- 150000003624 transition metals Chemical class 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 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
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 239000003446 ligand Substances 0.000 abstract description 17
- 229910052785 arsenic Inorganic materials 0.000 abstract description 13
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 6
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 125000003282 alkyl amino group Chemical group 0.000 abstract description 2
- -1 carbocyclic aryl Chemical group 0.000 abstract description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 abstract description 2
- 125000005241 heteroarylamino group Chemical group 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 229910052799 carbon Inorganic materials 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 238000000034 method Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CEQKTLFMTIWDBQ-UHFFFAOYSA-N C(C)[Fe](C1C=CC=C1)C1C=CC=C1 Chemical compound C(C)[Fe](C1C=CC=C1)C1C=CC=C1 CEQKTLFMTIWDBQ-UHFFFAOYSA-N 0.000 description 4
- 0 CC=C(C(OC(C=CI(C)=C1)=C1Br)=CC=*C)Br Chemical compound CC=C(C(OC(C=CI(C)=C1)=C1Br)=CC=*C)Br 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- RBFQJDQYXXHULB-UHFFFAOYSA-N arsane Chemical compound [AsH3] RBFQJDQYXXHULB-UHFFFAOYSA-N 0.000 description 3
- 229960004756 ethanol Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- SZXUFLXBJGFODO-AWEZNQCLSA-N (2s)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutanoic acid Chemical compound COCCCOC1=CC(C[C@@H](C(C)C)C(O)=O)=CC=C1OC SZXUFLXBJGFODO-AWEZNQCLSA-N 0.000 description 2
- SZXUFLXBJGFODO-UHFFFAOYSA-N 2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutanoic acid Chemical compound COCCCOC1=CC(CC(C(C)C)C(O)=O)=CC=C1OC SZXUFLXBJGFODO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SZXUFLXBJGFODO-CQSZACIVSA-N (2r)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutanoic acid Chemical compound COCCCOC1=CC(C[C@H](C(C)C)C(O)=O)=CC=C1OC SZXUFLXBJGFODO-CQSZACIVSA-N 0.000 description 1
- ANUJXWUVZHMJDL-UHFFFAOYSA-N 1-bromocyclopenta-1,3-diene;iron(2+) Chemical compound [Fe+2].BrC1=CC=C[CH-]1.BrC1=CC=C[CH-]1 ANUJXWUVZHMJDL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 1
- USWINTIHFQKJTR-UHFFFAOYSA-N 3-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(S(O)(=O)=O)C(O)=CC2=C1 USWINTIHFQKJTR-UHFFFAOYSA-N 0.000 description 1
- LRDIEHDJWYRVPT-UHFFFAOYSA-N 4-amino-5-hydroxynaphthalene-1-sulfonic acid Chemical compound C1=CC(O)=C2C(N)=CC=C(S(O)(=O)=O)C2=C1 LRDIEHDJWYRVPT-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- IBFIEAOXSAFFPS-QMMMGPOBSA-N CCO[C@@H](Cc1ccc[s]1)C(O)=O Chemical compound CCO[C@@H](Cc1ccc[s]1)C(O)=O IBFIEAOXSAFFPS-QMMMGPOBSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- MHIJWNWEFRCKIK-UHFFFAOYSA-N SC1CC=CC1 Chemical compound SC1CC=CC1 MHIJWNWEFRCKIK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- IMDXZWRLUZPMDH-UHFFFAOYSA-N dichlorophenylphosphine Chemical compound ClP(Cl)C1=CC=CC=C1 IMDXZWRLUZPMDH-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical group [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000012041 precatalyst Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
-
- 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
- C07F17/00—Metallocenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- 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
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- 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
- C07F19/00—Metal compounds according to more than one of main groups C07F1/00 - C07F17/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
技术领域
本发明涉及新型的基于茂金属的手性膦配体及其制备方法。此外,本发明还涉及可以用作不对称转化反应的催化剂或预催化剂的金属-配体络合物,以生成高对映体过量的产物。类似结构的胂也在本发明的范围内。
背景技术
某些已知的二膦配体仅在磷原子上表现出手性:
Marinetti15和Burk16分别报道了手性1,1′-双(磷杂环丁基)二茂铁(FerroTANE)的合成。FerroTANE已经成功地用于衣康酸酯和(E)-β-(酰氨基)丙烯酸酯的Rh-催化加氢17。
Mezzetti18和van Leeuwen19分别报道了P-手性二茂铁基二膦4a和4b。这两种配体对α-脱氢氨基酸衍生物的不对称加氢表现出极好的对映选择性(至多99%ee)。
Zhang报道了在3和4位具有缩酮取代基的1,1′-双(磷杂环戊基)二茂铁配体5。20该配体在β-脱氢氨基酸衍生物的加氢中表现出极好的对映选择性。该配体的缩酮基团对于获得高对映选择性是重要的,因为相 应的不具有缩酮基团的配体仅提供中度的ee。Zhang还开发了1,1′-双(二萘并磷杂环庚烯基)二茂铁配体,f-binaphane,其已经成功地用于无环芳亚胺的Ir-催化加氢。21
Reetz开发了联萘酚衍生的基于二茂铁的双亚膦酸盐配体622,其在衣康酸酯和α-脱氢氨基酸衍生物的Rh-催化加氢中表现出极好的反应性和对映选择性。
另一类已知的配体表现出平面和磷手性:
Van Leeuwen已经报道了结合平面和磷手性的基于二茂铁的双膦7a和7b23。这两种配体对不对称烯丙基烷基化表现出极好的对映选择性(至多99%ee)。
最近,Togni报道了第一个结合平面、磷和碳手性的基于二茂铁的三齿的膦配体12。24
我们以前报道过新型种类的手性膦和胂配体及其制备方法,其发表在以WO-A-2005/068477和WO-A-2005/068478公开的共同未决的申请中。
为用于对映选择性催化而设计改进的手性双膦配体是有利的。
发明内容
根据本发明,提供用于对映选择性催化的基于茂金属的膦或胂配体,该配体具有通式:
其中:
M为金属;
Z为P或Ar;
L为合适的连接基;
R1选自取代的和未取代的支链和直链烷基、烷氧基、烷基氨基,取代的和未取代的环烷基,取代的和未取代的环烷氧基,取代的和未取代的环烷基氨基,取代的和未取代的碳环芳基,取代的和未取代的碳环芳氧基、取代的和未取代的杂芳基,取代的和未取代的杂芳氧基,取代的和未取代的碳环芳氨基,以及取代的和未取代的杂芳氨基,其中所述杂原子或每个杂原子独立地选自硫、氮和氧;和
X*选自:
其中R、R2和R3独立地选自取代的和未取代的支链和直链烷基、取代的和未取代的环烷基、取代的和未取代的碳环芳基、以及取代的和未取代的杂芳基,其中所述杂原子或每个杂原子独立地选自硫、氮和氧。
R2和R3基团可以彼此取代,一起形成任选地取代的杂环体系。
M优选为Fe,但是Ru可以是另一个优选的M。
视具体情况而定,L优选包含在各个官能团处具有连接磷或砷的能力的双官能部分。视具体情况而定,连接基(L)通常源自双官能化合物,尤其是具有至少两个能够连接磷或砷的官能团的化合物。所述双官能化 合物可以适当地包含可以二锂化或反应形成双格氏试剂(di-Grignardreagent)或者可以另外处理形成双阴离子活性物质的化合物,其中所述双阴离子活性物质其后可以通过非对映异构选择方式直接与磷或砷结合以形成手性磷或砷,视具体情况而定。在这种情况下,所述双阴离子活性物质的第一阴离子组分可以与在根据本发明配体的第一配体前体中的磷(或砷)取代基结合,且所述双阴离子活性物质的第二阴离子组分可以再次以非对映异构选择方式与在所述配体的第二配体前体中的磷(或砷)取代基再次结合以形成根据本发明的手性磷(或砷)中心(第一和第二配体前体彼此相同)以通过连接基将第一和第二配体前体连接在一起。离去基团例如卤化物通常在第一和第二配体前体的磷(或砷)取代基上提供,其中所述离去基团在阴离子组分与磷(或砷)取代基结合时离去。下面路线说明该过程:
例如,L可以选自二茂铁和其它茂金属、二苯醚、呫吨、2,3-苯并噻吩、1,2-苯、琥珀酰亚胺、环酐等。方便地但是非必要地,该双阴离子连接基可以由相应的二卤代前体制备,例如:
二锂二苯醚
其中R’表示任何合适数量的任何一种或多种合适的取代基。
其它合适的双阴离子连接基可以是如下所示的:
但是,根据本发明,也可以选择二茂铁和其它茂金属用作连接基,而且有许多其它合适的也可以被选择的部分。
优选的R1包括苯基、甲基、环己基和叔丁基基团。
优选的R2和R3独立地包括甲基、乙基、异丙基和叔丁基基团。同时,R2和R3可以与和它们连接的氮一起形成任选取代的杂环例如吗啉、吡咯烷(pyrollidine)、哌啶及其衍生物。
本发明的某些配体源自Ugi胺,根据本发明的一个优选的配体(其中双阴离子连接基为二茂铁)可以如下所示:
Ugi胺基团完全被表示的同一优选的配体可以表示为:
本发明还涉及上述配体的对映体和非对映体。
根据本发明的配体还可以表示如下:
其中M、L、R1、X*如上定义,并且其中如果需要的话磷可以至少部分地被砷取代。
本发明的配体在磷(或砷)处显示出手性。优选地,在连接基分子的相对端处的磷(或砷)取代基的手性构型相同。
根据本发明,还提供包含与本发明的配体配位的过渡金属的过渡金属配合物。所述金属优选为VIb族或VIII族金属,尤其是铑、钌、铱、钯、铂或镍。
根据本发明的基于二茂铁的磷手性膦的合成可以依照如下路线实现:
其中,L为源自有机锂物质或格氏试剂L(G)2的连接基,其中X*和R1如上定义。相同的合成路线通常适用于根据本发明的其它基于茂金属的手性配体。
具体实施方式
现在将参照下列实施例更具体地说明本发明。
实施例1
1,1′双-[(SP,RC,SFe)(1-N,N-二甲基氨基)乙基二茂铁基)苯基膦基]二茂铁L1
在-78℃下将在戊烷(8.0ml,12.0mmol)中的1.5M的t-BuLi溶液加到在Et2O(20ml)中的(R)-N,N-二甲基-1-二茂铁基乙胺[(R)-Ugi胺](3.09g,12mmol)溶液中。加入完成后,将混合物温热到室温并在室 温下搅拌1.5h。然后再将混合物冷却到-78℃,并将苯基二氯膦(1.63ml,12.0mmol)一次全部加入。在-78℃下搅拌20分钟后,将混合物缓慢温热至室温,并在室温下搅拌1.5h。然后再将混合物冷却到-78℃,通过套管缓慢地加入1,1′二锂二茂铁悬浮液[由1,1′二溴二茂铁(1.72g,5.0mmol)和在戊烷中的1.5M的t-BuLi溶液(14.0ml,21.0mmol)在Et2O(20ml)中在-78℃下制备]。将混合物温热到室温并搅拌12h。通过加入饱和NaHCO3溶液(20ml)淬灭反应。分离有机层并经MgSO4干燥,在减压下除去溶剂。浓缩滤液。通过色谱(SiO2,己烷-EtOAc-Et3N=85:10:5)纯化残余物,得到橙色固体(3.88g,85%),为95%双-(SP,RC,SFe)标题化合物L1和5%(RP,RC,SFe-SP,RC,SFe)内消旋化合物的混合物。所述内消旋化合物可以通过使用色谱(SiO2,己烷-EtOAc-Et3N=85:10:5)更仔细地提纯而除去。橙/黄结晶固体的熔点为190~192℃。[α]D=-427°(c=0.005(g/ml),甲苯);1H NMR(CDCl3,400.13MHz):δ1.14(d,6H,J=6.7Hz),1.50(s,12H);3.43(m,2H);3.83(m,2H);3.87(m,2H);4.01(s,10H),4.09(t,2H,J=2.4Hz);4.11(m,2H);4.20(m,2H);4.28(m,2H);4.61(m,2H);4.42(d,2H,J=5.3Hz);7.18(m,6H);7.42(m,4H)ppm。13C NMR(CDCl3,100.61MHz):δ38.28,57.40(d,J=5.6Hz);67.02,69.04(d,J=4.0Hz);69.16(d,J=51.6Hz);69.66,71.60(d,J=4.8Hz),71.91(d,J=7.2Hz),72.18(d,J=5.6Hz),75.96(d,J=35.7Hz),79.96(d,J=6.4Hz),95.73(d,J=19.1Hz),127.32(d,J=7.9Hz),127.62,133.12(d,J=21.4Hz),139.73(d,J=4.0Hz)。31P NMR(CDCl3,162MHz):δ-34.88(s)。实测值:C,65.53;H,5.92;N3.01。C50H54Fe3N2P2的计算值;C,65.81;H,5.97;N,3.07。HRMS(10eV,ES+):C50H55Fe3N2P2[M+H]+计算值:913.1889;实测值:913.1952。
标记SP是指磷的S构型,RC是指碳的R构型(或其它附属构型),SFe是指平面手性元素的S构型。
注:为了保持该研究在分配磷的构型时的整体一致性,我们指定Ugi胺(1-N,N-二甲基氨基)乙基二茂铁基)部分1级优先级、引入的锂或格氏亲核试剂(在上述实施例中为锂二茂铁)2级优先级和其余基团3级优先级。该方法不总是与严格步骤一致。使用单晶x-射线晶体学检验了这些分配和所提出的磷构型。
实施例2
2,2′双-[(SP,RC,SFe)(1-N,N-二甲基氨基)乙基二茂铁基)苯基膦基]-4-甲苯 基醚L2
除了将2,2′二锂-4-甲苯基醚悬浮液[通过已知方法由2,2′二溴-4-甲苯基醚(1.78g,5.0mmol)和在戊烷中的1.5M的t-BuLi溶液(14.0ml,21.0mmol)在Et2O(20ml)中在-78℃下制备]而不是1,1′二锂二茂铁用作连接基试剂之外,使用与上述类似的步骤。
黄色结晶固体[α]D=-105°(c=0.005(g/ml),甲苯);1H NMR(CDCl3,400.13MHz):δ1.23(d,6H),1.72(s,12H);2.28(s,6H);4.11(s,10H);4.12(m,2H重叠);4.28(m,2H);4.31(m,4H);4.35(m,2H,重叠);7.00-7.30(m,14H)ppm。31P NMR(CDCl3,162MHz):δ-40.69(br s)ppm。
实施例3
2,7-二-叔丁基-4,5-双-[(SP,RC,SFe)(1-N,N-二甲基氨基)乙基二茂铁基)苯基膦基]-9,9-二甲基-9H-呫吨
除了将2,7-二-叔丁基-4,5-二锂-9,9-二甲基-9H-呫吨悬浮液[通过已知方法由2,7-二-叔丁基-4,5-二溴-9,9-二甲基-9H-呫吨和在戊烷中的1.5M的t-BuLi溶液在Et2O中在-78℃下制备]而不是1,1′二锂二茂铁用作连接基试剂之外,使用与上述类似的步骤。
橙/黄色结晶固体;1H NMR(CDCl3,400.13MHz):δ1.12(s,18H);1.13(m,6H重叠);1.78(s,6H);1.98(s,12H);3.99(m,2H);4.15(s,10H重叠);4.32(m,2H);4.41(m,4H);7.00-7.40(m,14H)ppm。31P NMR (CDCl3,162MHz):δ-41.78(br s)ppm。HRMS(10eV,ES+):C63H75Fe2N2OP2[M+H]+计算值:1049.4053;实测值:1049.4222。
合成路线1.0式(Vl)底物的合成路线
实施例4
(Z)-2-乙氧基-3-(噻吩-3-基)丙烯酸
按照(Vol.8,No.6,2004,Organic Research&Development)的步骤并加以调整,该化合物合成如下:将氯乙酸乙酯(44.8ml,421mmol)和无水乙醇(30ml)冷却到10~12℃。在N2下在12~16℃时用25分钟加入在乙醇中的乙醇钠溶液(21%w/w,165ml)。加入完成后,将反应混合物温热到25℃并搅拌1h。然后将混合物冷却到10℃,随后在10~14℃下用0.5h分批加入固体NaOEt(33.3g,488mmol)。然后加入乙醇(20ml),随后加入碳酸二乙酯(31ml,256mmol)。然后将浆冷却到0~5℃,然后用1h的时间加入3-噻吩醛(20.2g,179.5mmol)。加入完成后,在油浴中在40℃下搅拌混合物15h。然后将浆冷却到10~15℃,加入水(40ml),随后加入NaOH水溶液(55ml的10M溶液)。然后在20℃下在pH值为14时搅拌所得的浆3h。然后用水(60ml)稀释混合物并在45℃时将其置于减压下除去大部分乙醇和一些水。然后在冰浴中将所得的稠浆冷却到4℃并用逐滴的浓HCl(115ml)处理。然后在室温下搅拌所得的浆1.5h,用EtOAc(2×200ml)萃取,用水、盐水洗有机层,然后干燥(硫酸钠)。在减压下蒸发溶剂,得到深褐色残余物。将其溶于5M的NaOH(250ml)中,并用EtOAc(100ml)洗该溶液。然后将该碱性水溶液冷却到4℃,用浓HCl(11M)酸化到pH为4~6。用乙醚(3×200ml)萃取产物,用盐水洗,干燥(硫酸钠)并在减压下除去溶剂。然后通过二氧化硅垫过滤残余物(己烷:EtOAc为90:10的洗脱剂)。减压下除去溶剂,然后由Et2O/己烷重结晶该残余物,得到标题化合物,为黄色晶体(79%)。熔点为88~89℃。 1H NMR(CDCl3,250MHz)δ11.16(1H,br s,COOH),7.73-7.75(1H,dd, j=0.5Hz,Ar),7.44-7.47(1H,dd,J=1Hz,Ar),7.25-7.28(1H,m,Ar),7.18(1H,s,CH=C),3.96-4.05(2H,q,J=7Hz,CH 2 CH3),1.35(3H,t,J=7Hz,CH2 CH 3 ),)。实测值:C,54.64;H,5.08;C9H10SO3计算值:C,54.54;H,5.08。M/z[(Cl)222(M)+30%,223(M+H)+50%,240(M+NH4)+100%;实测值:223.09705;C12H15O4所需:223.09155]。M/z[(Cl)198(M)+22%,199(M+H)+50%,216(M+NH4)+100%]。
使用与上述类似的步骤制备下列化合物。
实施例5
(Z)-2-乙氧基-3-(噻吩-2-基)丙烯酸
粉红色结晶固体(77%)。熔点103~104℃。1H NMR(CDCl3,250MHz)δ12.15(1H,br s,COOH),7.48(1H,s CH=C),7.40(1H,m,Ar),7.29((1H,m,Ar)。7.08(1H,m,Ar),4.11(2H,q,J=7Hz,CH 2 CH3),1.48(3H,t,J=7Hz,CH2 CH 3 )。实测:C,54.82;H,5.11,S,16.00;C9H10SO3计算值:C,54.54;H,5.08;S,16.16]。M/z[(Cl)222(M)+30%,223(M+H)+50%,240(M+NH4)+100%;实测值:223.09705;C12H15O4所需:223.09155。M/z[(Cl)198(M)+22%,199(M+H)+50%,216(M+NH4)+100%]。
实施例6
(Z)-3-(4-氰基苯基)-2-乙氧基丙烯酸
白色结晶固体。熔点171~172℃。1H NMR(CDCl3,250MHz)δ10.75(1H,br s,COOH),7.87(2H,m,Ar),7.67(2H,m,Ar),7.07(1H,s,CH=C),4.09-4.12(2H,q,CH 2 CH3),1.38(3H,t,J=5和7.5Hz,CH2 CH 3 )。实测值:C,66.28;H,5.12;N,6.42。C12H11NO3计算值:C,66.36;H,5.09;NS,6.45]。M/z[(Cl)217(M)+250%,218(M+H)+200%,235(M+NH4)+100%。
实施例7
(Z)-3-(3-(苄氧基)-4-甲氧基苯基)-2-乙氧基丙烯酸
粉红色结晶固体。熔点147~148℃。1H NMR(CDCl3,250MHz)δ11.82(1H,br s,COOH),7.66(1H,s CH=C),7.24-7.57(8H,m,Ar),5.17(2H,s,CH2O),3.83-3.99(2H,q,CH 2 CH3),3.94(3H,s,OCH3),1.22-1.29(3H,t,CH2 CH 3 )。实测值:C,69.40;H,6.18;C19H20O5计算值;C,69.51;H,6.15。M/z[(Cl)328(M)+20%,329(M+H)+45%,346(M+NH4)+100%。
实施例8
(Z)-2-乙氧基-3-(3-甲氧基苯基)丙烯酸
白色结晶固体。熔点99~100℃。1H NMR(CDCl3,250MHz)δ12.07(1H,br s,COOH),7.56(1H,br s,Ar),7.29(2H,m,Ar),7.15(1H,s,CH=C),6.92(1H,m,Ar),4.07(2H,q,J=7.5Hz,CH2),3.83(3H,s,OCH3),和1.37(3H,t,J=7Hz)。实测值:C,65.13;H,6.37,C12H14O4计算值;C,64.86;H,6.35。M/z[(Cl)222(M)+30%,223(M+H)+50%,240(M+NH4)+100%;[实测值:223.09705;C12H15O4所需;223.09155]。
实施例9
通常的加氢筛选方法:
将配体(3.25×10-3mM)置于45ml的高压釜中,将该容器置于真空/Ar循环下。然后用氩吹扫该容器。然后通过注射器/针加入[(COD)2Rh]BF4在MeOH中的脱气溶液(5ml的0.64mM的溶液),将橡胶塞置于容器上以保持惰性气氛。将该混合物搅拌10分钟,得到澄清的黄色溶液。然后通过注射器/针加入初始原料在MeOH中的脱气溶液,同时小心地努 力保持惰性气氛。然后将高压釜连接到Parr3000多容器反应器系统,然后将其置于Ar(5巴)下,排气,同时搅拌,重复这个过程3次。最后一次排气后,将混合物置于H2(50巴)下,再次小心地排气。然后将混合物置于H2(50巴)下,密封并加热到所希望的温度保持所需的时间。之后,冷却反应混合物并将容器排气。然后,对0.5~1.0ml的试样量进行分析。
实施例10
(S)-2-(3-(3-甲氧基丙氧基)-4-甲氧基苄基)-3-甲基丁酸
将1,1′双-[(RP,SC,RFe)L1(0.0063g,0.0069mmol)、[(COD)2Rh]BF4(0.0025g,0.0061mmol)和(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸(2g,6.49mmol)置于45ml的高压釜中。将该容器置于真空/Ar循环下。然后用氩吹扫该容器并将橡胶塞置于容器上以保持惰性气氛。然后通过套管加入脱气MeOH(10ml),小心地保持容器中的惰性气氛。然后密封容器并开始搅拌。然后将容器置于Ar(5巴)下,排气,重复这个过程3次。然后将高压釜置于H2(50巴)下,再次小心地排气。然后将混合物置于H2(50巴)下,密封并加热至40℃保持12h。之后,冷却反应混合物并将容器排气。然后,对0.5~1.0ml的试样量进行分析。转化率>98%,e.e>98.5%(主要对映体的第二流出峰(second runningpeak))。
1H NMR(CDCl3,250.13MHz):δ1.01(m,6H),1.95(m,1H);2.05(m,2H);2.45(m,1H);2.78(m,2H);3.35(s,3H),3.55(m,2H);3.83(s,3H);4.10(m,2H);6.65-6.80(m,3H)。
用于2-(3-(3-甲氧基丙氧基)-4-甲氧基苄基)-3-甲基丁酸的e.e.测定的HPLC法
Chiralpak-AD柱(250mm×4.6mm),94%的己烷,3%的2-甲基-2-丙醇和3%的叔戊醇,流速:1ml/min,230nm。S-酸13.15分钟(最大峰为双-[(RP,SC,RFe)]1),R-酸14.01分钟,初始原料42.73分钟。
用于2-(3-(3-甲氧基丙氧基)-4-甲氧基苄基)-3-甲基丁酸(甲酯)-重氮甲烷衍生的e.e.测定的HPLC法
将搅拌棒和1ml粗氢化反应混合物的试样量置于10ml的小瓶中。在强搅拌下将在己烷(2M)中的三甲基甲硅烷基重氮甲烷逐滴加到反应混合物中,随着良好的气体放出,重氮甲烷溶液的正黄色消失。继续该逐滴过程,直到反应混合物变成黄色且气体放出停止。然后加入纯乙酸(15~30μl-小心加入太多乙酸而产生过量气体放出),于是混合物变成非常浅的黄色。然后以巴斯德移液管取约1/3的该混合物通过润湿的二氧化硅小垫过滤,并用一点己烷/IPA(80:20)洗涤。然后使用HPLC分析所得的溶液:Chiralpak-AD柱(250mm×4.6mm),95%的己烷,5%的异丙醇,流速:1ml/min,230nm。产物对映体;9~10分钟,初始原料;14~16分钟。
注:对映体的洗脱顺序与非衍生酸的分析相反。
1,1′双-[(SP,RC,SFe)]L1产生(R)-2-(3-(3-甲氧基丙氧基)-4-甲氧基苄基)-3-甲基丁酸
1,1′双-[(RP,SC,RFe)]L1产生(S)-2-(3-(3-甲氧基丙氧基)-4-甲氧基苄基)-3-甲基丁酸
(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸
实施例11
表1.0在50巴H2压力下用双-[(SP,RC,SFe)]L1对(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸的对映选择性加氢的结果。
1反应在MeOH中进行20h
2反应在MeOH中进行5h
3反应在MeOH中进行14h
实施例12
表2.0在50巴H2压力下用双-[(SP,RC,SFe)]L1对(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸的对映选择性加氢的结果
实施例13
表3.0在50巴H2压力下用双-[(SP,RC,SFe)]L1对(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸的对映选择性加氢的结果(使用固体加入法*)。
注:在所有情况中观察到>98%的转化率
*将所有固体(底物、配体和金属源)置于容器中,然后加入溶剂
实施例14
已经发现,对于所描述的酸底物的对映选择性氢化,最优选含有柔性连接基单元的配体。
表4.0在MeOH中在50巴H2压力下用配体L1-L2对(E)-2-(3-(3-甲氧基丙氧基)-4-甲氧基亚苄基)-3-甲基丁酸的对映选择性加氢的结果
实施例15
用于(S)-2-乙氧基-3-(噻吩-2-基)丙酸(作为甲酯)的e.e.测定的HPLC法
衍生后:
Chiralpak-AD柱(250mm×4.6mm),95%的己烷,2.5%的2-甲基-2-丙醇和2.5%的叔戊醇,流速:1ml/min,236nm。对映体5.44分钟和5.81分钟(最大峰为双-[SP,RC,SFe)]1)。
实施例16
用于(S)-3-(3-(苄氧基)-4-甲氧基苯基)-2-乙氧基丙酸的e.e.测定的HPLC法
Chiralpak-AD柱(250mm×4.6mm),93%的己烷,7%的异丙醇,流速:1.2ml/min,235nm。对映体11.71分钟、13.33分钟(最大峰为双-[(RP,SC,RFe)]1),初始原料36.68分钟。
实施例17
表5.0在48巴H2压力下12h用双-[(SP,RC,SFe)]1对(Z)-[-(3-苄氧基-4-甲氧基苯基)]-2-乙氧基丙烯酸的对映选择性加氢的结果。
所有反应在MeOH中进行
所有反应获得>98%的转化率
实施例18
用于(S)-2-乙氧基-3-(噻吩-3-基)丙酸的e.e.测定的HPLC法
Chiralpak-AD柱(250mm×4.6mm),99%的己烷,1%的异丙醇,流速:0.7ml/min,统一在235~239nm。对映体9.71分钟、10.88分钟(最大峰为双-[(RP,SC,RFe)]1),初始原料16.35分钟。
实施例19
用于(S)-2-乙氧基-3-(3-甲氧基苯基)丙酸(作为甲酯)的e.e.测定的HPLC法
衍生后:
Chiralpak-AD柱(250mm×4.6mm),95%的己烷,2.5%的2-甲基-2-丙醇和2.5%的叔戊醇,流速:1ml/min,280-290nm联合(integrated280-290nm)。对映体7.49分钟和10.00分钟(最大峰为双-[(SP,RC,SFe)]1)。
实施例20
表6.0在50巴H2压力下用双-[(SP,RC,SFe)]1对各种(Z)-取代的3-芳基-2-乙氧基丙烯酸底物的对映选择性加氢的筛选结果。
所有反应在MeOH中进行
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Nobuhiko Oohara, Kosuke katagiri, et al..A novel P-chirogenic phosphine ligand, (S,S)-1,2-bis-[(ferrocenyl)methylphosphino]ethane:synthesis and use inrhodium-catalyzed asymmetric hydrogenation and palladium-catalyzed asymmetric allylic alkylation..Tetrahedron: Asymmetry14.2003,142171-2175. * |
Ulrike Nettekoven, Michael Widhalm, et al..Steric and electronic ligand perturbations in catalysis:asymmetric allylic substitution reactions using C2-symmetricalphosphorus-chiral (Bi)ferrocenyl donors..J. Org. Chem.66.2001,66759-770. * |
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