CN103889995B - 一类新型含氮配体金属钌络合物及其制备方法和用途 - Google Patents
一类新型含氮配体金属钌络合物及其制备方法和用途 Download PDFInfo
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- CN103889995B CN103889995B CN201280014922.7A CN201280014922A CN103889995B CN 103889995 B CN103889995 B CN 103889995B CN 201280014922 A CN201280014922 A CN 201280014922A CN 103889995 B CN103889995 B CN 103889995B
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- ketone
- hydrogen
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- 239000003446 ligand Substances 0.000 title claims abstract description 78
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 31
- 239000002184 metal Substances 0.000 title claims abstract description 31
- 239000012327 Ruthenium complex Substances 0.000 title claims description 3
- 238000004519 manufacturing process Methods 0.000 title abstract description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 57
- -1 unsaturated alkyl ketone Chemical class 0.000 claims abstract description 56
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000001257 hydrogen Substances 0.000 claims abstract description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 22
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 18
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 14
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
- 239000000460 chlorine Substances 0.000 claims abstract description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000002576 ketones Chemical class 0.000 claims abstract description 13
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 12
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 12
- 150000003624 transition metals Chemical class 0.000 claims abstract description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000011630 iodine Substances 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 229910010277 boron hydride Inorganic materials 0.000 claims abstract description 7
- 238000010276 construction Methods 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 60
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 18
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 12
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 11
- 150000001721 carbon Chemical group 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims description 7
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- ZPFKRQXYKULZKP-UHFFFAOYSA-N butylidene Chemical group [CH2+]CC[CH-] ZPFKRQXYKULZKP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 2
- WIWBLJMBLGWSIN-UHFFFAOYSA-L dichlorotris(triphenylphosphine)ruthenium(ii) Chemical compound [Cl-].[Cl-].[Ru+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 WIWBLJMBLGWSIN-UHFFFAOYSA-L 0.000 claims 1
- 150000002736 metal compounds Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 9
- 238000009903 catalytic hydrogenation reaction Methods 0.000 abstract description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract description 6
- 241001597008 Nomeidae Species 0.000 abstract description 4
- 150000004696 coordination complex Chemical class 0.000 abstract description 4
- WSGCRAOTEDLMFQ-UHFFFAOYSA-N nonan-5-one Chemical group CCCCC(=O)CCCC WSGCRAOTEDLMFQ-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 106
- 229910052786 argon Inorganic materials 0.000 description 53
- 239000000047 product Substances 0.000 description 36
- 238000003756 stirring Methods 0.000 description 26
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 230000014759 maintenance of location Effects 0.000 description 20
- 239000007789 gas Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000011521 glass Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 229960001866 silicon dioxide Drugs 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 230000006837 decompression Effects 0.000 description 15
- 229910052698 phosphorus Inorganic materials 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 11
- 238000001514 detection method Methods 0.000 description 11
- DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 11
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 11
- 230000005587 bubbling Effects 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 239000012159 carrier gas Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000000376 reactant Substances 0.000 description 9
- 238000004679 31P NMR spectroscopy Methods 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 7
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 229960004132 diethyl ether Drugs 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 5
- 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 4
- RZZDRSHFIVOQAF-UHFFFAOYSA-N [4-(5-diphenylphosphanyl-1,3-benzodioxol-4-yl)-1,3-benzodioxol-5-yl]-diphenylphosphane Chemical compound C=12OCOC2=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=C2OCOC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RZZDRSHFIVOQAF-UHFFFAOYSA-N 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 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 description 3
- GYZZZILPVUYAFJ-UHFFFAOYSA-N phanephos Chemical compound C1CC(C(=C2)P(C=3C=CC=CC=3)C=3C=CC=CC=3)=CC=C2CCC2=CC=C1C=C2P(C=1C=CC=CC=1)C1=CC=CC=C1 GYZZZILPVUYAFJ-UHFFFAOYSA-N 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-Phenylethanol Natural products OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 239000005922 Phosphane Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- ONQRMOMMIPJWKD-UHFFFAOYSA-N [N].[N].P Chemical compound [N].[N].P ONQRMOMMIPJWKD-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000008365 aromatic ketones Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229910000064 phosphane Inorganic materials 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- HCBRTCFUVLYSKU-URFUVCHWSA-N (1r)-2-tert-butyl-1-[(1r)-2-tert-butyl-1,3-dihydroisophosphindol-1-yl]-1,3-dihydroisophosphindole Chemical compound CC(C)(C)P1CC2=CC=CC=C2[C@@H]1[C@H]1C2=CC=CC=C2CP1C(C)(C)C HCBRTCFUVLYSKU-URFUVCHWSA-N 0.000 description 1
- SJNUZTRUIDRSJK-KNCCTNLNSA-N (1s,2r)-1-tert-butyl-2-[(1s,2r)-1-tert-butylphospholan-2-yl]phospholane Chemical compound CC(C)(C)[P@]1CCC[C@@H]1[C@@H]1[P@@](C(C)(C)C)CCC1 SJNUZTRUIDRSJK-KNCCTNLNSA-N 0.000 description 1
- YMRKZKDKJJCIHH-UHFFFAOYSA-N (4-diphenylphosphanylpyrrolidin-3-yl)-diphenylphosphane Chemical compound C1NCC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YMRKZKDKJJCIHH-UHFFFAOYSA-N 0.000 description 1
- GTIXSUJKFAATAE-UHFFFAOYSA-N (r)-c3-tunephos Chemical compound C=12C(C(=CC=C3)P(C=4C=CC=CC=4)C=4C=CC=CC=4)=C3OCCCOC2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 GTIXSUJKFAATAE-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- CTYPJIUQROQJBG-UHFFFAOYSA-N 4-diphenylphosphanylpentan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)CC(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 CTYPJIUQROQJBG-UHFFFAOYSA-N 0.000 description 1
- NVXLIZQNSVLKPO-UHFFFAOYSA-N Glucosereductone Chemical compound O=CC(O)C=O NVXLIZQNSVLKPO-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 229910019891 RuCl3 Inorganic materials 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- VCHDBLPQYJAQSQ-UHFFFAOYSA-N [5-(diphenylphosphanylmethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CC1OC(C)(C)OC1CP(C=1C=CC=CC=1)C1=CC=CC=C1 VCHDBLPQYJAQSQ-UHFFFAOYSA-N 0.000 description 1
- PQHKXSOICTYGQD-UHFFFAOYSA-N [5-(diphenylphosphanylmethyl)pyrrolidin-3-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CC(NC1)CC1P(C=1C=CC=CC=1)C1=CC=CC=C1 PQHKXSOICTYGQD-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- UQXKXGWGFRWILX-UHFFFAOYSA-N ethylene glycol dinitrate Chemical compound O=N(=O)OCCON(=O)=O UQXKXGWGFRWILX-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
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- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
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- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
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- B01J2231/60—Reduction reactions, e.g. hydrogenation
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- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
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Abstract
本发明涉及新型含膦、氮配体金属钌络合物及其制备方法和用途。本发明提供具新结构的含有膦配体、具NH2-N(sp2)结构特征的氮配体的过渡金属络合物,金属钌络合物的总结构式(I)为:[RuLmL′XY],其中X和Y可以相同也可以不同。X可以是氯、溴、碘或氢,Y可以是氯、溴、碘或BH4;本发明还提供了上述过渡金属络合物的制备方法及应用。本发明所述的金属钌络合物及含氮配体合成方法简便,可以用于催化不对称氢化反应,尤其应用于α位是芳基或不饱和烷基酮、二芳基酮及其类似物、α位为叔丁烷基酮、α位为杂原子基团的酮、β-N,N-二甲氨基-α苯乙酮及其衍生物和其它芳基-烷基酮类化合物的催化不对称氢化反应。上述金属钌络合物应用于酮的催化氢化时,该金属络合物可以原位制备。
Description
技术领域
本发明涉及一类新型含膦、氮配体金属钌络合物及其制备方法和用途。具NH2-N(sp2)结构特征的双氮配体与过渡金属钌配位形成双膦双氮配体过渡金属络合物,可以用于催化不对称氢化反应和转移氢化反应,尤其是用于酮类化合物的不对称催化氢化反应。
背景技术
不对称催化氢化反应是当前不对称合成领域中的热点[Ohkuma,T.;Kitamura,M.;Noryori,R.(1999)AsymmetricHydrogenation.In:CatalyticAsymmetricSynthesis,2ndEd.(Ed.:Ojima,I.).Wiley-VCH,NewYork,2000],[TheHandbookofHomogeneousHydrogenation(Ed.:deVries,J.G.,Elsevier,C.J.).Wiley-VCH:Weinheim,2007;Vol.1–3.],目前已经越来越多地被应用于工业生产[AsymmetricCatalysisonIndustrialScale(Ed.:Blaser,H.-U.;Schmidt).Wiley-VCH,Weinheim,2004]。
手性醇类化合物是制药、农药和精细化工等行业中重要的中间体,其中酮类化合物的不对称氢化反应是制备手性醇的最有效方法之一。不对称催化氢化还原酮的一个突破性进展是Noyori小组实现的,他们运用金属-配体双功能外围活化的概念,制备了一种结构为trans-[RuCl2(phosphane)(1,2-diamine)]的络合物,在碱(如t-BuOK或KOH)的存在下,可高效、高对映选择性地催化酮类底物的不对称氢化反应[Noyori,R.;Takeshi,O.;Hirohito,O.Shohei,H.;Takao,I.J.Am.Chem.Soc.1995,117,2675],[Noyori,R.;Ohkuma,T.;Douce,H.;Murata,K.;Yokozawa,T.;Kozawa,M.;Katayama,E.;England,A.F.;Ikariya,T.,Angew.Chem.Int.Ed.1998,37,1703]。由于催化剂对底物的普适性较差,人们设计和合成了许多手性双膦配体并在酮类化合物的不对称氢化反应中取得非常好的结果[Jing,W.;Hua,C.;Waihim,K.;Rongwei,G.;Zhongyuan,Z.;Chihung,Y.;Chan,S.C.,J.Chem.Soc.2002,67,7908],[Jing,W.;Jian,X.;Rongwei,G.;Chihung,Y.;Chan,S.C.,Chem.Eur.J.2003,9,2963],[Jian,H.X.;Xin,L.W.;Fu,Y.;Shuo,F.Z.;Bao,M.F.;Hai,F.D.;Zhou,Q.L.J.Am.Chem.Soc.2003.125,4404],[Mark,J.;William,H.;Daniela,H.;Christophe,M.;Antonio,Z.G.Org.Lett.2000,26,4173]。
而最近Noyori小组设计一种新的催化剂RuCl2(phosphane)(α-picolylamine),通过改变双胺配体为NH2-N(sp2)双氮配体,可高效、高对映选择性地催化α位是大位阻叔烷基的酮的氢化生成手性叔烷基甲醇[Ohkuma,T.;Sandoval,C.A.;Srinivasan,R.;Lin,Q.;Wei,Y.;K.;NoyoriR.J.Am.Chem.Soc.2005,127,8288.],这是可以高效催化氢化这一类特殊底物的催化剂[Ohkuma,T.;Sandoval,C.A.;Noyori,R.WO2006046508A1,2006]。值得一提的是,手性叔烷基甲醇可用于生产手性表面活性剂等重要的化合物,而使用传统的双膦双氮Ru催化剂RuCl2(tolbinap)(dpen)组合催化这一反应时,反应产率和对映选择性均低于20%。
通过对NH2-N(sp2)结构特征的双氮配体过渡金属络合物进一步研究[Sandoval,C.A,LiYuehui.WO2009149670A1,2009],合成了一种新结构的过渡金属络合物,且其在甲苯、THF等非质子性溶剂或异丙醇等质子性溶剂中均能高效地催化芳香酮的氢化反应。而目前通过双功能外围活化作用的氢化催化剂只在质子性溶剂中具有催化活性。
发明内容
本发明的目的是提供一类具新结构的含有膦配体、具NH2-N(sp2)结构特征的氮配体的过渡金属络合物,尤其是金属钌络合物。
本发明的另一目的是提供上述过渡金属络合物的制备方法。
本发明的目的还将提供上述过渡金属络合物的应用。该类过渡金属络合物可以用于不对称催化氢化反应。尤其是用于α位大位阻的酮、苯乙酮及其衍生物,α位是芳基或不饱和烷基的酮,二芳基酮及其类似物,α位为叔丁烷基的酮、α位为杂原子基团的酮、β-N,N-二甲氨基-α苯乙酮及其衍生物和其它芳基-烷基酮类化合物的不对称催化氢化反应或不对称转移氢化反应。
本发明的过渡金属络合物可以在质子性溶剂、非质子性溶剂或者混合溶剂中进行不对称催化氢化反应。
本发明所涉及的金属钌络合物的总结构式(Ⅰ)为:[RuLmL′XY],其中X和Y可以相同也可以不同。X可以是氯、溴、碘或氢,Y可以是氯、溴、碘或BH4。
L为膦配体,选自以下结构:
1)通式为R1R2R3P的单齿膦配体,其中R1,R2,R3可以相同也可以不同,为1~6个碳原子的脂肪烃或6~12个碳原子的芳香烃基团;
2)通式为的双齿膦配体,其中R4为手性或非手性的有机碳氢基团;R5,R6,R7,R8可以相同也可以不同,为1~10个碳原子的脂肪烃或芳香性基团;
当m为2时,膦配体为两个相同的选自上述1)中的单齿膦配体;当m为1时,膦配体选自上述2)中的双齿膦配体;
进一步地,对于双齿膦配体结构R4可选自但不局限于以下结构:
L′为双齿氮配体,选自以下结构(II~V):
R9,R10可以相同也可以不同。R9,R10可以是氢或1~12个碳原子的烃基。所述的双齿氮配体II-V具有一个手性中心时可以是R构型或S构型,具有两个手性中心时可以是(R,R)构型或(S,S)构型。上述1~12个碳原子的烃基可以是甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、环戊基、环己基、环庚基、苯基、苄基、烷基取代的苄基。当为环烃基时,可以是亚丙基或亚丁基。R11,R12,R13可以是氢或1~12个碳原子的烷基、芳基、芳基烷基;脂肪烃基选自甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、环戊基、环己基、环庚基;芳香烃选自苯基、取代苯基;芳基烷基选自苄基、烷基取代的苄基。
当双齿氮配体选自结构Ⅲ时,Z可以是NH,也可以是O。
A可以单独为氢,1~8个碳原子的烷基、烷氧基、芳基、卤素原子、硝基、氨基、磺酸基。n为1~4的整数,等于未取代的芳香环的碳原子数。上述1~8个碳原子的烷基选自甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、环戊基、环己基、环庚基、氟甲基、三氟甲基;上述1~8个碳原子的烷氧基选自甲氧基、乙氧基、丙氧基、异丙氧基、叔丁氧基、正丁氧基;上述1~8个碳原子的芳基选自苯基、取代苯基、苄基、取代苄基。
所述的双齿含氮配体可以比较方便地通过有机合成方法获得。
所述的金属钌络合物结构式(Ⅰ)还进一步可以描述如下:
在所有结构式中,络合物可以是顺式(cis)或反式(trans)构型,P代表与金属钌(Ru)配位的膦配体,定义如前所述。本发明中的膦配体包括但不限于三苯基膦、BINAP及具有二萘基或取代二萘基的双膦类似物、BIPHEP及具有二苯基或取代二苯基的双膦类似物、JOSIPHOS及具有二茂铁或取代二茂铁结果的双膦类似物、DIPAMP,DIOP,PPM,BDPP,DuPhos,TangPhos,TunePhos,SegPhos,ChiraPhos,SkewPhos,PhanePhos,Norphos,DuanPhos,Cn-TunePhos等。
结构式代表双齿氮配体,选自结构式II、III、IV或V,其中R9,R10,Z的定义如前所述。X可以是氯、溴、碘或氢,Y可以是氯、溴、碘或BH4。
所述的络合物(Ⅰ)的制备可以在有机溶剂中和反应温度为20℃~120℃下,由金属钌化合物、双氮配体、双膦配体或单膦配体反应0.5~20小时获得,其中,金属钌化合物、双氮配体、双膦配体或单膦配体的摩尔比为1:1~3:1~5。当采用双氮和单膦配体时,金属钌化合物、双氮配体、单膦配体的摩尔比为1:1~3:3~5,推荐1:2:4;当采用双氮和双膦配体时,金属钌化合物、双氮配体、双膦配体的摩尔比为1:1~3:1~3,推荐1:2:2。所述的金属钌化合物是Ru的卤化物或其衍生物,如RuX2(PPh3)3,RuX3,其中X为氯、溴或碘。
所述的金属钌络合物的制备过程可具体地由下面的反应式表示:
上述金属钌络合物制备过程中,当Y为BH4时,反应式如下:
上述反应式中,P、Z和R1~R10的定义如前所述。
本发明所述的方法中使用的有机溶剂可以是苯、甲苯、二甲苯、三甲苯、乙腈、乙醚、四氢呋喃、乙二醇二甲醚、三氯甲烷、二氯甲烷、甲醇、乙醇、异丙醇、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、N-甲基吡咯烷酮等。
本发明所述的金属钌络合物及含氮配体合成方法简便,可以用于催化不对称氢化反应,尤其应用于α位是芳基或不饱和烷基酮、二芳基酮及其类似物、α位为叔丁烷基酮、α位为杂原子基团的酮、β-N,N-二甲氨基-α苯乙酮及其衍生物和其它芳基-烷基酮类化合物的催化不对称氢化反应。上述金属钌络合物应用于酮的催化氢化时,该金属络合物可以原位制备。
具体实施方式
通过以下实施例有助于进一步理解本发明,但并不限制本发明的内容。
使用C2对称的双膦配体(DIOP,BINAP,MeO-BIPHEP,SEGPHOS,PhanePHOS,DIPAMP,DuPHOS,BDPP,TunePHOS,CHIRAPHOS,PPM,PYRPHOS)制备络合物的方法以化合物[RuCl2(C6H6)]、RuCl2(PPh3)3和trans-RuCl2(NBD)(py)2作为起始原料,制备工艺参考文献[Noyori,R.;Takeshi,O.;Hirohito,O.Shohei,H.;Takao,I.J.Am.Chem.Soc.1995,117,2675;Akotsi,O.M.;Metera,K.;Reid,R.D.;McDonald,R.;Bergens,S.H.Chirality2000,12,514–522]。使用C1对称的双膦配体(JosiPHOS,WalPHOS,MandyPHOS)制备络合物的方法以化合物RuCl2(PPh3)3为起始原料,而RuCl2(PPh3)3可以比较方便地以RuCl3水合物和PPh3制备得到[Steohenson,T.A.;Wilkinson,G.J.Inorg.Nucl.Chem.1966,28,945-956]。上述络合物的制备方法参考文献[Baratta,W.;Ballico,M.;Chelucci,G.;Siega,K.;Rigo,P.Angew.Chem.Int.Ed.2008,47,4362-4365]。所有的合成反应均在氩气保护下进行,所有溶剂使用前均经重蒸。具体以络合物(8-15)的制备进行了比较详细的描述,但并不限制本发明的内容。
膦配体化学名称缩略表:
BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl
DIOP=4,5-Bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane
MeO-BIPHEP=5,5′-Dichloro-6,6′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-biphenyl
SEGPHOS=5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole
PhanePHOS=4,12-Bis(diphenylphosphino)-[2.2]-paracyclophane
DIPAMP=1,2-Bis[(2-methoxyphenyl)(phenyl)phosphino]ethane
Me-DuPHOS=1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene
Tunephos=1,13-Bis(diphenylphosphino)-7,8-dihydro-6H-dibenzo[f,h][1,5]dioxonin
BDPP=2,4-Bis(diphenylphosphino)pentane
CHIRAPHOS=Bis(diphenylphosphino)butane
PYRPHOS=3,4-bis(diphenylphosphino)-Pyrrolidine
Norphos=2,3-Bis(diphenylphosphino)-bicyclo[2.2.1]hept-5-ene
PPM=4-(diphenylphosphino)-2-[(diphenylphosphino)methyl]-Pyrrolidine
Josiphos=1-[Diarylphosphano]-2-[1-(dicyclohexylphosphano)ethyl]ferrocene
金属钌络合物的合成
本发明的制备方法可以进一步用以下代表性络合物的制备过程体现。
实施例1反式-RuCl2[(S)-SEGPHOS][β-bimaH][(S)-8]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(S)-SEGPHOS20mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入β-bimaH5.3mg(0.0328mmol)和2.6ml氩气脱气处理的DCM(二氯甲烷)-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌12小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物23.3mg(产率76%)。31PNMR(121MHz,CDCl3):δ55.4ppm(d,J(P,P)=36.1Hz),40.7ppm(d,J(P,P)=35.9Hz)。
实施例2反式-RuCl2[(S,S)-DIOP][(R,R)-ACHC-Oxazole][(SS,RR)-9]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(S,S)-DIOP16.4mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入(R,R)-ACHC-Oxazole5.3mg(0.0328mmol)和2.6ml经氩气脱气处理的DCM-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌12小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物20.9mg(产率71%)。31PNMR(121MHz,CDCl3,20℃)δ40.7ppm(d,2J(P,P)=42.6Hz),28.6ppm(d,2J(P,P)=42.6Hz)。
实施例3反式-RuCl2[(R)-SEGPHOS][(S)-Me-β-bimaH][(R,S)-10]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(R)-SEGPHOS20mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入(S)-Me-β-bimaH5.3mg(0.0328mmol)和2.6ml经氩气脱气处理的DCM-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌12小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物26.4mg(产率83%)。31PNMR(121MHz,CDCl3,20℃):δ49.58ppm(d,J=38.7Hz),47.32ppm(d,J=38.7Hz)。
实施例4反式-RuCl2[(S)-MeO-BIPHEP][(S)-Bn-β-bimaH][(S,S)-11]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(S)-MeO-BIPHEP19.1mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入(S)-Bn-β-bimaH7.8mg(0.0328mmol)和2.6ml经氩气脱气处理的DCM-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌12小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物28.7mg(产率88%)。31PNMR(121MHz,CDCl3,20℃)δ48.42ppm(d,J=29.7Hz),46.18ppm(d,J=29.7Hz)。
实施例5顺式-RuCl2[(S,S)-DIOP][D-β-bimaH][(SS)-12]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(S,S)-DIOP16.4mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入D-β-bimaH5.8mg(0.0328mmol)和2.6ml经氩气脱气处理的DCM-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌15小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物21.1mg(产率74%)。31PNMR(121MHz,CDCl3,20℃)δ55.76ppm(d,J(P,P)=42.3Hz),δ54.3ppm(d,J(P,P)=41.1Hz),δ53.0ppm(d,J(P,P)=42.3Hz),δ29.0ppm(d,J(P,P)=42.3Hz),33.3ppm(d,J(P,P)=42.3Hz),31.0ppm(d,2J(P,P)=43.6Hz)。
实施例6反式-RuCl2[(S,S)-DIOP][(R,R)-ACPC-Imidazole][(SS,RR)-13]的制备
在氩气保护下,将[RuCl2(C6H6)]28.2mg(0.0164mmol)和(S,S)-DIOP16.4mg(0.0328mmol)悬浮在2ml经氩气脱气处理的DMF中,100℃下搅拌1小时;在50℃、真空除去溶剂,得到褐色固体;然后,加入(R,R)-ACHC-Oxazole5.3mg(0.0328mmol)和2.6ml经氩气脱气处理的DCM-甲醇混合溶剂(DCM:甲醇=10:3),再加入Et3N9.9mg(0.0984mmol),氩气保护下室温搅拌12小时;真空除去溶剂,加入3mlDCM,过滤;滤液减压蒸馏浓缩至约0.5ml,再加入3ml正己烷沉淀,过滤,3mL乙醚洗涤两次,真空干燥,得到产物20.4mg(产率70%)。31PNMR(121MHz,CDCl3,20℃)δ40.9ppm(d,2J(P,P)=42.6Hz),28.4ppm(d,2J(P,P)=42.6Hz)。
实施例7反式-RuCl2[(S,S)-DIOP][(R,R)-ACHC-Imidazole][(SS,RR)-14]的制备
制备方法同实施例2。
产率81%。31PNMR(121MHz,CDCl3,20℃)δ(ppm)42.6,27.8。
实施例8反式-RuCl2[(S,S)-DIOP][(R)-i-Pr-β-BIMAH][(SS,R)-15]的制备
制备方法同实施例2。
产率75%。31PNMR(121MHz,CDCl3,20℃)δ(ppm)40.5,28.1。
催化不对称氢化反应
实施例9苯基乙酮的不对称氢化(Ⅰ)
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)络合物(S)-8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌11小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为97.6%,转化率91.3%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.38-7.25(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=125℃;(R)-异构体保留时间=14.7min;(S)-异构体保留时间=15.2min。
实施例10苯基乙酮的不对称氢化(Ⅱ)
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)络合物(SS,RR)-13及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌20小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为96%,转化率99.5%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.38-7.25(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=125℃;(R)-异构体保留时间=14.7min;(S)-异构体保留时间=15.2min。
实施例11苯基乙酮的不对称氢化(Ⅲ)
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)络合物(SS,RR)-14及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌18小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为96%,转化率99.7%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.38-7.25(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=125℃;(R)-异构体保留时间=14.7min;(S)-异构体保留时间=15.2min。
实施例12苯基乙酮的不对称氢化(Ⅳ)
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)络合物(SS,R)-15及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌7小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为96.9%,转化率100%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.38-7.25(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=125℃;(R)-异构体保留时间=14.7min;(S)-异构体保留时间=15.2min。
实施例134’-甲氧基苯基乙酮的不对称催化氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入150mg(1mmol)4’-甲氧基苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌14小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为94.8%,转化率99%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.31(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速0.8mL/min;柱温=140℃;(R)-异构体保留时间=27min;(S)-异构体保留时间=27.8min。
实施例143’-溴代苯基乙酮的不对称催化氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.1mL3’-溴代苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌12小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物3’-溴代苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为98.5%,转化率99.5%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.52(s,1H),7.41-7.37(m,1H),7.29-7.17(m,2H),4.87(q,J=6.6Hz,1H),2.20(br,1H),1.50(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.1mL/min;柱温=150℃;(R)-异构体保留时间=18.9min;(S)-异构体保留时间=19.3min。
实施例152’-甲基苯基乙酮的不对称催化氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.11mL2’-甲基苯基乙酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌18小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物2’-甲基苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为94.3%,转化率87.6%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.50(d,J=7.8Hz,1H),7.29-7.24(m,2H),6.09(q,J=6.6Hz,1H),2.32(s,1H),2.11(br,1H),1.44(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=135℃;(R)-异构体保留时间=14.2min;(S)-异构体保留时间=15.8min。
实施例162’-氯代二苯基甲酮的不对称催化氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入210mg2’-氯代二苯基甲酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌8小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物2’-氯代二苯基甲醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为92.5%,转化率91.1%,绝对构型为R构型。1HNMR(300MHz,CDCl3)δ7.58(d,J=7.5Hz,1H),7.39-7.17(m,8H),6.19(s,1H),2.50(br,1H);高效液相色谱(ChiralcelOD-H柱):检测波长λ=254nm;流动相,环己烷:2-丙醇=93:7;室温;流速1.0mL/min;(R)-异构体保留时间=8.5min;(S)-异构体保留时间=10.2min。
实施例17频哪酮的不对称催化氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的100mL玻璃反应釜内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)频哪酮和3.0mL新蒸馏的甲苯,氩气鼓泡脱气5min后在氩气保护下转入玻璃反应釜;先通入高纯氢气至10atm然后小心地释放氢气,驰气-充气重复三次,最后充氢气至8atm并维持,25℃快速搅拌8小时,监控H2的消耗量;达到预设的反应时间,释放反应釜内的氢气,猝灭反应;通过手性GC柱进行产物频哪醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为95.3%,转化率82%,绝对构型为R构型。气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速0.2mL/min;柱温=50℃;(R)-异构体保留时间=22.7min;(S)-异构体保留时间=24.0min。
催化不对称转移氢化反应
实施例18苯基乙酮的不对称转移氢化
在氩气保护下,在一个具有磁力搅拌子的经120℃预干燥的20mLSchlenk管内加入1.0mg(0.001mmol)催化剂8及7.5mg(0.067mmol)t-BuOK;抽真空至少5min后通入氩气进行置换,重复3次;在另一个经120℃预干燥的Schlenk管中加入0.12mL(1mmol)苯基乙酮和3.0mL新蒸馏的异丙醇,氩气鼓泡脱气5min后在氩气保护下转入上述20mLSchlenk管内;80℃下搅拌12小时;反应液经硅胶柱过滤,减压蒸馏除去溶剂。通过手性GC柱进行产物1-苯基乙醇转化率和ee值的检测,产物的绝对构型由旋光仪确定。经气相色谱分析,产物的对映体过量值为94.7%,转化率93%,绝对构型为S构型。1HNMR(300MHz,CDCl3)δ7.38-7.25(m,芳氢,5H),4.87(q,J=6.6Hz,1H),2.03(br,1H),1.48(d,J=6.6Hz,3H);气相色谱:BETA-DEXTM120熔融硅胶毛细管柱(df=0.25m,0.25mmi.d.×30m,Supelco):P=100.3kPa;进样口温度250℃;检测器温度300℃;氮载气流速1.0mL/min;柱温=120℃;(R)-异构体保留时间=14.7min;(S)-异构体保留时间=15.2min。
对上述不对称氢化反应的说明:
上述不对称氢化反应中所用的溶剂可以是以下的一种或其混合:苯、甲苯、二甲苯、三甲苯、四氢呋喃、二氯甲烷、乙醚、甲醇、乙醇、异丙醇、正丙醇、正丁醇、异丁醇、叔丁醇、乙腈、乙二醇二甲迷、氯仿、二甲基亚砜、N-甲基吡咯烷、N,N-二甲基甲酰胺等。
所用的碱可以是以下的一种或其混合:氢氧化钠、氢氧化钾、叔丁醇盐、叔丁醇钠、叔丁醇锂、叔丁醇铯、碳酸铯、碳酸钠、碳酸钾、碳酸氢钠、碳酸氢钾、磷酸钾、磷酸氢钾、磷酸二氢钾、氟化钾、氢化钠、氢化钾、氢化钙、三乙胺、二异丙基乙基胺、四甲基乙二胺、N,N-二甲基苯胺、N,N-二乙基苯胺、1,4-二氮杂二环[2,2,2]辛烷(DABCO)、二氮杂二环十二烷(DBU)、1,4-二甲基哌嗪、1-甲基哌啶、1-甲基吡咯、喹啉或吡啶等。
所述的反应可以耐受少量的水。
所述的反应可以耐受含有某些特定官能团如酯键[-C(=O)O-]、氨基(-NH2)的化合物。
所述的反应中涉及的底物可以是含杂原子的芳香酮。
所述的反应的时间可以为0.1-48小时,氢气的压力可以为1-80atm。
Claims (12)
1.一类含氮配体金属钌络合物,总结构式(Ⅰ)为:[RuLmL′XY],其中X和Y相同或不同,X是氯、溴、碘或氢,Y是氯、溴、碘或BH4;
L为膦配体,选自以下结构:
1)通式为R1R2R3P的单齿膦配体,其中R1,R2,R3相同或不同,为1~6个碳原子的脂肪烃或6~12个碳原子的芳香烃基团;
2)通式为的双齿膦配体,R5,R6,R7,R8相同或不同,为1~10个碳原子的脂肪烃或芳香烃基团;
R4选自以下结构:
当m为2时,膦配体为两个相同的选自上述1)中的单齿膦配体;当m为1时,膦配体选自上述2)中的双齿膦配体;
L′为双齿氮配体,其结构为III:
R9,R10相同或不同,所述的双齿氮配体III具有一个手性中心时是R构型或S构型,具有两个手性中心时是(R,R)构型或(S,S)构型;R9,R10是甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、环戊基、环己基、环庚基、苯基、苄基、烷基取代的苄基,当为环烃基结构时,是亚丙基或亚丁基;
Z是NH,或是O;
A为氢、甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、环戊基、环己基、环庚基、氟甲基、甲氧基、乙氧基、丙氧基、异丙氧基、叔丁氧基、正丁氧基、苯基、苄基、卤素原子、硝基、氨基、磺酸基,n为1~4的整数,等于未取代的芳香环的碳原子数。
2.如权利要求1所述的一类含氮配体金属钌络合物,在所有结构式中,络合物是顺式(cis)或反式(trans)构型。
3.如权利要求1所述的一类含氮配体金属钌络合物,具有结构式(Ⅵ):[RuL2L′XY],L为单膦配体,选自权利要求1中的1);L′为双齿氮配体,结构式为III;X是氯、溴、碘或氢,Y是氯、溴、碘、氢或BH4;X、Y形成顺式或反式的过渡金属络合物。
4.如权利要求1所述的一类含氮配体金属钌络合物,具有结构式(Ⅶ):[RuLL′XY],L为双膦配体,选自权利要求1中的2);L′为双齿氮配体,结构式为III;X是氯、溴、碘或氢,Y是氯、溴、碘、氢或BH4;X、Y形成顺式或反式的过渡金属络合物。
5.如权利要求1所述的一类含氮配体金属钌络合物的制备方法,在反应温度20℃-120℃下,由过渡金属化合物、双氮配体、双膦配体或单膦配体有机溶剂中反应0.5~20小时获得;过渡金属钌化合物、双氮配体、双膦配体或单膦配体的摩尔比为1:1~3:1~5。
6.如权利要求5所述的一类含氮配体金属钌络合物的制备方法,其特征是所述的过渡金属钌化合物是[RuX2(C6H6)]2、RuX3或RuCl2(PPh3)3,所述的X是Cl、Br或I。
7.如权利要求5所述的一类含氮配体金属钌络合物的制备方法,其特征为当采用单膦配体时,过渡金属钌化合物、双氮配体、单膦配体的摩尔比为1:1~3:1~5。
8.如权利要求5所述的一类含氮配体金属钌络合物的制备方法,其特征为当采用双膦配体时,过渡金属钌化合物、双氮配体、双膦配体的摩尔比为1:1~3:1~3。
9.如权利要求1所述的一类含氮配体金属钌络合物的用途是用于催化不对称转移氢化反应或不对称氢化反应,所述的过渡金属钌络合物用于α位大位阻的酮、苯乙酮,α位是芳基或不饱和烷基的酮,二芳基酮,α位为叔丁烷基的酮、α位为杂原子基团的酮、β-N,N-二甲氨基-α苯乙酮的不对称氢化反应或不对称转移氢化反应。
10.如权利要求9所述的一类含氮配体金属钌络合物的用途,不对称转移氢化反应或不对称氢化反应所用的溶剂是质子溶剂或非质子溶剂或该二者的混合物,质子溶剂为甲醇、乙醇、异丙醇、正丙醇、正丁醇、异丁醇、叔丁醇;非质子溶剂为苯、甲苯、二甲苯、三甲苯、四氢呋喃、二氯甲烷、乙醚、乙腈、乙二醇二甲醚、氯仿、二甲基亚砜、N-甲基吡咯烷酮。
11.如权利要求5所述的一类含氮配体金属钌络合物的制备方法,其特征为当采用单膦配体时,过渡金属钌化合物、双氮配体、单膦配体的摩尔比为1:2:4。
12.如权利要求5所述的一类含氮配体金属钌络合物的制备方法,其特征为当采用双膦配体时,过渡金属钌化合物、双氮配体、双膦配体的摩尔比为1:2:2。
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