CN1329405C - 新型二膦及其与过渡金属形成的络合物以及该类络合物在不对称合成中的应用 - Google Patents
新型二膦及其与过渡金属形成的络合物以及该类络合物在不对称合成中的应用 Download PDFInfo
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- CN1329405C CN1329405C CNB028188136A CN02818813A CN1329405C CN 1329405 C CN1329405 C CN 1329405C CN B028188136 A CNB028188136 A CN B028188136A CN 02818813 A CN02818813 A CN 02818813A CN 1329405 C CN1329405 C CN 1329405C
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- 229910052751 metal Inorganic materials 0.000 title claims abstract description 25
- 239000002184 metal Substances 0.000 title claims abstract description 25
- 238000011914 asymmetric synthesis Methods 0.000 title description 2
- 150000002739 metals Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 129
- 239000003054 catalyst Substances 0.000 claims abstract description 28
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 14
- 150000004696 coordination complex Chemical class 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 239000010948 rhodium Substances 0.000 claims description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 21
- 238000005984 hydrogenation reaction Methods 0.000 claims description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 13
- 229910020366 ClO 4 Inorganic materials 0.000 claims description 12
- 239000010949 copper Substances 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 229910052703 rhodium Inorganic materials 0.000 claims description 12
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052707 ruthenium Inorganic materials 0.000 claims description 10
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- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 229910052802 copper Inorganic materials 0.000 claims description 8
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims description 8
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- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 238000005755 formation reaction Methods 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 3
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 2
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- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 16
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- 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 11
- 239000012074 organic phase Substances 0.000 description 11
- -1 2-benzofuryl Chemical group 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
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- 239000007864 aqueous solution Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000009834 vaporization Methods 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical class C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 150000002900 organolithium compounds Chemical class 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 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 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 3
- 238000007259 addition reaction Methods 0.000 description 3
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- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
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- ASUOLLHGALPRFK-UHFFFAOYSA-N phenylphosphonoylbenzene Chemical class C=1C=CC=CC=1P(=O)C1=CC=CC=C1 ASUOLLHGALPRFK-UHFFFAOYSA-N 0.000 description 3
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- CJSJVLSIOQOCGR-UHFFFAOYSA-N 6-diphenylphosphoryl-2,3-dihydro-1,4-benzodioxine Chemical compound C=1C=CC=CC=1P(C=1C=C2OCCOC2=CC=1)(=O)C1=CC=CC=C1 CJSJVLSIOQOCGR-UHFFFAOYSA-N 0.000 description 2
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- 229940122361 Bisphosphonate Drugs 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
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- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000000746 allylic group Chemical group 0.000 description 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
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- 150000004663 bisphosphonates Chemical class 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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- 238000002425 crystallisation Methods 0.000 description 2
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- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
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- PONXTPCRRASWKW-KBPBESRZSA-N diphenylethylenediamine Chemical compound C1([C@H](N)[C@@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-KBPBESRZSA-N 0.000 description 2
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- AFQSOHSPTULSFS-FGSKAQBVSA-N ethene;(z)-4-hydroxypent-3-en-2-one;rhodium Chemical compound [Rh].C=C.C=C.C\C(O)=C\C(C)=O AFQSOHSPTULSFS-FGSKAQBVSA-N 0.000 description 2
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- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
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- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
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- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
- YAXWOADCWUUUNX-UHFFFAOYSA-N 1,2,2,3-tetramethylpiperidine Chemical compound CC1CCCN(C)C1(C)C YAXWOADCWUUUNX-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
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- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
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- QPQGTZMAQRXCJW-UHFFFAOYSA-N [chloro(phenyl)phosphoryl]benzene Chemical compound C=1C=CC=CC=1P(=O)(Cl)C1=CC=CC=C1 QPQGTZMAQRXCJW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
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- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
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- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- GGRQQHADVSXBQN-FGSKAQBVSA-N carbon monoxide;(z)-4-hydroxypent-3-en-2-one;rhodium Chemical compound [Rh].[O+]#[C-].[O+]#[C-].C\C(O)=C\C(C)=O GGRQQHADVSXBQN-FGSKAQBVSA-N 0.000 description 1
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- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
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- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002681 magnesium compounds Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- 238000009991 scouring Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
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Classifications
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- B01J31/1805—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 nitrogen
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Abstract
本发明涉及外消旋型或光学纯型的式(I)新型二膦衍生物,其中:R1与R2为(C5-C7)环烷基、选择性地具有取代基的苯基或5元杂芳基;而且A为(CH2-CH2)或CF2。本发明还涉及式(I)化合物在制备金属络合物时作为配体的用途以及含有至少一个式(I)配体的手性金属催化剂,所述金属络合物可用作不对称性催化中的手性催化剂。
Description
技术领域
本发明涉及新型的外消旋或手性二膦类化合物,所述二膦类化合物可在金属络合物的合成中用作二齿配位体,更具体地说,所述二膦类化合物可作为二齿配位体用于催化剂的合成,该催化剂是特别为催化不对称氢化反应而设计的。
不对称性催化的好处在于无需拆分外消旋混合物就可通过不对称诱导作用直接制备纯光活异构体。现有技术已经描述了某些二膦配体,这些二膦配体常用于制备用作以下反应的不对称催化的金属络合物:氢化反应、羰基化反应、氢化硅烷化反应以及C-C键形成反应或甚至烯丙胺的不对称异构化反应。特别要提到的是,专利号EP850945公开的专利申请中描述了2,2’-双(二苯基膦基)-1,1’-双萘基(BINAP)或者[(5,6),(5’,6’)-双(亚甲基二氧基)二苯基-2,2’-二基]双(二苯基膦)(SEGPHOS)。
期望可以研制出一种新的手性配体,以提高反应的选择性(非对映选择性以及对映选择性)。
发明内容
因而本发明涉及外消旋型或光学纯型的式(I)新型二膦衍生物,所述式(I)是:
其中:
-R1与R2各自独立地是:
(C5-C7)环烷基;选择性地具有以下一个或一个以上的取代基的苯基:(C1-C4)烷基、(C1-C4)烷氧基或双(C1-C4)烷基氨基;或者是具有卤素原子作为取代基的苯基,或
5元杂芳基;而且
-A为亚乙基(CH2-CH2)或CF2基团。
5元杂芳基可以理解为例如2-呋喃基、3-呋喃基、2-苯并呋喃基或3-苯并呋喃基。
烷基可以理解为线性的或支化的饱和烃基。
(C1-C4)烷基可以理解为含有1-4个碳原子的烷基。
术语“烷氧基”表示O-烷基自由基,其中烷基的定义如上。
卤素原子可以理解为氯、溴、氟或碘原子。
根据一个特有的特征,本发明涉及式(I)化合物,其中R1与R2是完全相同的,而且更具体地说,其中R1与R2完全相同并且均为苯基。
本发明的式(I)化合物可由以下流程图1所示的工艺流程制备,其中R1、R2与A如式(I)所定义,R为(C1-C4)烷基或者选择性地具有取代基的苯基。
流程图1
光学纯型即(R)或(S)或者外消旋型的式(I)化合物可由还原相应的光学纯型即(R)或(S)或者外消旋型的式(IIA)化合物而制得:
其中R1、R2与A如式(I)所定义,所述还原是例如在胺如三丁基胺存在下与一种还原剂如三氯硅烷进行反应。
光学纯型的化合物(IIA)是通过例如形成带有(-)-L-二苯甲酰酒石酸或(+)-D-二苯甲酰酒石酸或其他手性酸的络合物来拆分外消旋型的化合物(IIA)而得到的,这个过程如现有技术中对于此类拆分所述。
所述的对映异构体也能够经由手性相色谱法分离而制得。
作为合成式(I)化合物时的中间体,外消旋型或光学纯型的式(IIA)化合物是新的化合物,而且构成了本发明的一个组成部分。
式(IIA)化合物能够由式(IIIA)化合物与例如叔丁基锂等有机锂化合物在三氯化铁或其他适合的氧化剂存在下反应制得,所述式(IIIA)是:
其中R1、R2与A如式(I)所定义。
化合物(IIA)也能够通过其衍生物(IIIA)经由两个步骤制备:碘化化合物(IIIA)以获得式(IIIC)碘化衍生物,然后借助于铜进行乌尔曼式偶联(Ullman-type coupling)反应。
其中R1与R2完全相同的化合物(IIA)能够以第三种方法制得,即由式(IIB)化合物制得,在所述式(IIB)化合物中R为(C1-C4)烷基或者取代的或未取代的苯基。在这第三种方法中,化合物(IIB)与分子式R1Li或R1MgX的有机金属化合物接触,其中R1如式(I)所定义,X为卤素原子。
化合物(IIB)能以外消旋体或手性体形式存在,与式(IIA)化合物相似,所述化合物(IIB)能够经由手性酸或手性相色谱法拆分。
式(IIB)化合物是新的化合物,也构成了本发明的一个组成部分。
其中R1与R2完全相同的化合物(IIA)也能够由式(IIB)化合物通过一个两步骤方法制备,其中第一步是将所述化合物(IIB)在溶剂存在下与亚硫酰氯反应,以获得其卤素衍生物式(IIC):
而第二步是将所述化合物(IIC)与一种有机金属化合物反应,具体地说,是与分子式为R1Li的有机锂化合物或分子式为R1MgX的有机镁化合物反应,以获得期望的式(IIA)化合物,所述R1Li和R1MgX中的R1如式(I)所定义,X为卤素原子。
式(IIIA)化合物可通过将式(IVA)膦氧化而制得:
其中R1、R2与A如式(I)所定义,所述氧化是通过式(IVA)膦与过氧化氢的甲醇溶液的反应或借助本领域熟知的其他能氧化膦的试剂而完成的。
膦(IVA)本身能够通过相应的溴化合物(V)与例如正丁基锂等有机锂化合物反应,然后再与膦R1R2PCl在接近-70℃条件下反应而制得,其中R1和R2如式(I)所定义。
化合物(IIIA)也可直接由化合物(V)与镁的四氢呋喃溶液反应以形成格氏试剂,然后与膦R1R2P(O)Cl反应而制得,其中R1和R2如式(I)所定义。
化合物(IIIA)也可从化合物(V)经由化合物(IVA)而得到,其方法是通过化合物(V)与镁的四氢呋喃溶液反应以形成格氏试剂,然后与R1和R2如式(I)所定义的膦R1R2PCl反应,再与过氧化氢的甲醇溶液或借助本领域熟知的其他能氧化膦的试剂进行氧化反应。
式(IIIA)、式(IIIC)与式(IVA)化合物是新的化合物,同样也构成了本发明的一个组成部分。
式(IIB)衍生物能够由衍生物(IIIB)一步制得,其方法是在三氯化铁或其他合适的氧化剂存在下将衍生物(IIIB)与例如仲丁基锂等有机锂化合物反应,所述衍生物(IIIB)中的R如衍生物(IIB)中所定义。
式(IIB)衍生物还能够由衍生物(IIIB)通过两步反应制得,其方法是将衍生物(IIIB)碘化以得到碘化衍生物(IIID),然后采用铜使碘化衍生物(IIID)进行乌尔曼式反应,从而得到衍生物(IIB)
式(IIIB)化合物可由化合物(V)与镁的醚溶液反应以形成有机镁化合物,后者再与衍生物Cl-P(O)(OR)2反应而得到,其中R如(IIB)中所定义。
式(IIIB)化合物也能够由式(V)化合物在约100-160℃条件下、在衍生物P(OR)3存在下与氯化镍反应制得,所述P(OR)3中的R如(IIB)中所定义。
A为CF2的化合物(IIIB)是新的化合物,其构成了本发明的一个组成部分。A为亚乙基且R为苯基、甲基或(C3-C4)烷基的化合物(IIIB)是新的化合物,其同样也构成了本发明一个组成部分。
本发明的另一个特征涉及式(I)化合物作为制备金属络合物中的配体的用途,所述的金属络合物在不对称性催化中用作手性催化剂。
本发明进一步涉及含有至少一个式(I)配体的手性金属催化剂,所述式(I)配体为外消旋型或优选光学纯型。当式(I)配体为外消旋型时,该金属络合物的手性经由另一种手性配体获得,比如手性二胺类配体。
本发明的金属催化剂可用于以下反应的不对称性催化:氢化反应、不饱和化合物的硼氢化反应、烯烃异构化反应和烯丙型烷基化反应,总之还有C-C键的形成反应(例如硼酸的1,4-加成反应)、4-戊烯醛类的不对称环化反应(J.Org.Chem.2000,65,5806-16)、烯-炔环化反应(Angew.Chem.,Int.Ed.2001,40(1),249-53)、烯醇类的烯丙型取代反应(Angew.Chem.,Int.Ed.2000,39(19),3494-7)以及芳香族α-氨基酸类的形成反应(Angew.Chem.,Int.Ed.2000,39(22),4114-6)。
具体实施方式
在本发明的一个优选实施方案中,所述金属催化剂被用于C=O、C=C以及C=N双键的氢化反应。能被用于此类反应的所述催化剂优选为铑、钌、钯、铱、镍或铜催化剂。
在一个具体实施方案中,本发明涉及式(VI)手性金属催化剂:
MmLnXpSq (VI)
其中:
-M为选自铑(Rh)、钌(Ru)、铱(Ir)、钯(Pd)、镍(Ni)和铜(Cu)的一种金属;
-L为手性化合物(I);以及
-X、S、m、n、p和q定义如下:
·若M=Rh,则X=Cl、Br或I;m=n=p=2;q=0;
·若M=Ru,则:X=-OC(O)CH3;m=n=1;p=2;q=0;
或X=Br;m=n=1;p=2;q=0;
或X=Cl;S=N(CH2CH3)3;m=n=2;p=4;q=1;
或X=甲代烯丙基;m=n=1;p=2;q=0;
或X=Cl;S=吡啶;m=n=1;p=q=2;
或X=Cl;S=手性1,2-二胺;m=n=1;p=q=2或p=2,q=1;
·若M=Ir,则X=Cl、Br或I;m=n=p=2;q=0;
·若M=Pd,则:X=Cl;m=n=1;p=2;q=0;
或X=π-烯丙基;m=n=p=2;q=0;
·若M=Ni,则X=Cl、Br或I;m=n=1;p=2;q=0。
可提到的手性二胺的实例为(R,R)-与(S,S)-1,2-二苯基亚乙基二胺。
本发明的一个具体特征涉及式(VII)金属催化剂:
[MrLsZtWu]Yv (VII)
其中:
-M为选自铑(Rh)、钌(Ru)、铱(Ir)、钯(Pd)和铜(Cu)的一种金属;
-L为手性化合物(I);以及
-Z、W、r、s、t、u和v定义如下:
·若M=Rh,则Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6、OTf或BPh4;r=s=t=v=1;u=0;
·若M=Ru,则:Z=Cl、Br或I;W=苯或对甲基异丙基苯;Y=Cl、Br或I;r=s=t=u=v=1;
或Y=BF4、ClO4、PF6或BPh4;r=s=1;t=u=0;v=2;
或Z=Cl;Y=NH2(C2H5)2;r=s=2;t=5;u=0;v=1;
·若M=Ir,则Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6或BPh4;r=s=v=1;t=1;u=0;
·若M=Pd,则Y=BF4、ClO4、PF6或BPh4;r=s=v=1;t=u=0;
·若M=Cu,则Y=PF6或ClO4;r=s=v=1;t=u=0。
普遍优选铑和钌催化剂,选自下列化合物的铑和钌催化剂是特别优选的:
-式(VI)的化合物:
其中M=Ru,而且X=Br;m=n=1;p=2;q=0;
或X=Cl;S=N(CH2CH3)3;m=n=1;p=4;q=1;
或X=Cl;S=吡啶;m=n=1;p=q=2;以及
-式(VII)的化合物:
其中M=Rh,而且Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6、OTf或BPh4;r=s=t=v=1;u=0。
含有本发明的式(I)的配体以及一种选自铑、钉、钯、铱、镍或铜的金属的所述催化剂能够通过本领域技术人员熟知的文献所描述的方法来制备。尤其可参考专利号EP850945下公开的专利申请。
本发明的催化剂通常从起始的金属络合物开始制备,该金属络合物的性质根据所选择的金属而变化。
在采用铑催化剂的情况下,起始络合物为例如下列化合物之一:Rh(cod)2OTf;[Rh(cod)Cl]2,其中cod表示1,5-环辛二烯;Rh(acac)(CO)2,其中acac表示乙酰丙酮化物;或Rh(acac)(C2H4)2。
如RuCl3、Ru(cod)(甲代烯丙基)2、[RuCl2(苯)]2以及[RuCl2(nbd)]x之类的络合物可用于制备所述铑催化剂,其中nbd代表降冰片二烯,x为一个整数。还可提到的是Ru(acac)3与[RuCl2(cod)]x,其中x为一整数。
一般地说,本发明的金属催化剂是通过混合起始金属络合物、式(I)配体和经脱气的无水有机溶剂并选择性地使该反应混合物处于15℃到150℃之间的温度范围内反应10分钟-5小时而制得,优选反应温度为30-120℃之间。
可用的溶剂为芳香烃类(例如苯、甲苯或二甲苯)、酰胺类(例如甲酰胺、二甲基甲酰胺、二甲基乙酰胺、N-甲基-2-吡咯烷酮或六甲基磷酰胺)、醇类(例如乙醇、甲醇、正丙醇或异丙醇)以及其混合物、酮类(例如丙酮、甲乙酮、甲基异丁基酮或环己酮)、醚类(例如四氢呋喃)以及线性的、支化的或环化的烷烃(例如戊烷、己烷或甲基环己烷)。
然后,以常规技术(过滤或结晶)将该催化剂分离,然后将其用于不对称反应中。然而,该催化剂也能就地制备。当使用以这种方法制备的催化剂时,待催化的反应能够在无需对催化剂实施中间分离的条件下进行。
本发明进一步涉及本发明的金属催化剂在催化不对称性反应中的用途,尤其是该类催化剂在对氢化反应和C-C键的形成反应进行催化中的用途。采用该类催化剂的不对称性氢化反应方法或C-C键的不对称形成方法也构成了本发明一个组成部分。这些反应是在本领域技术人员熟知的条件下进行的。
例如,当进行不对称性氢化反应时,将不饱和底物溶于含有所述催化剂的溶剂中,置于氢气压力下反应。反应操作条件类似于现有技术中金属催化剂的常用条件。例如,使用的氢气压力在1-150巴之间,温度在0℃-150℃之间。底物对催化剂的摩尔比通常为1/100至1/100,000之间,优选为1/100至1/5000。
由本发明的配体制备的铑络合物尤其更适用于烯烃异构化反应的不对称性催化、C=C双键氢化反应的不对称性催化以及硼酸的1,4-加成反应的不对称性催化。
由本发明的配体制备的钌络合物尤其更适用于羰基键、C=C双键以及C=N双键的氢化反应的不对称性催化。
在下列的实施例中,“制备例”表示描述中间体合成的例子,“实施例”表示描述本发明的式(I)、式(VI)或式(VII)化合物的合成的例子。这些实施例意在说明本发明而决不是用于限制本发明的范围。熔点在Koffler工作台上测定,核磁共振光谱的数值由相对于TMS计算得出的化学位移δ来表征,通过与峰信号有关的质子数目与峰信号的形状(s代表单峰,d代表二重峰,t代表三重峰,m代表多重峰,dd代表双二重峰,ddd代表双(双二重峰),q代表四重峰,qd代表双四重峰,J代表偶合常数)来表征。操作频率以及所使用溶剂对于每一化合物均有指出。质谱结果是通过惠普7989A仪器获得。
使用以下缩写:RT=室温,DMSO=二甲基亚砜,Ph=苯基,THF=四氢呋喃,Me=甲基,Et=乙基,acac=乙酰丙酮化物,Tf=三氟甲磺酸盐,S-DPED=(S,S)-二苯基乙二胺。
用于确定化合物的命名原则沿用化学文摘所推荐的命名法。
制备例1
6-溴-2,3-二氢-1,4-苯并二氧杂苯,化合物V
将35g 1,4-苯并二噁烷与200ml无水二甲基甲酰胺置于0℃的氩气环境中。然后在其中分批加入54.9g N-溴代丁二酰亚胺。当其逐渐的回升至室温时,将该反应混合物持续搅拌24小时。减压蒸发除去溶剂后,将所得的白色固体以二氯甲烷洗涤。以50ml饱和硫酸钠水溶液处理后,再以50ml氯化钠水溶液洗涤,然后在硫酸镁上干燥。再减压蒸发除去溶剂之后,得到黄色油状物(定量产率)。
EI质谱:M+=214
1H NMR(200MHz)CDCl3:4.25(4H,s);6.74(1H,d);6.93(1H,dd);7.02(1H,d)
制备例2
6-溴-2,3-二氢-1,4-苯并二氧杂苯,化合物V
化合物V同样也能够以下述方法制备:
将5g 1,4-苯并二噁烷与100ml无水四氢呋喃置于避光的氩气环境中。然后加入5.12g 1,3-二溴-5,5-二甲基乙内酰脲。将该反应混合物在室温下避光搅拌18小时。将一半的四氢呋喃蒸发除去后,加入50ml戊烷。过滤后,重复该操作三次,然后将溶剂在减压下蒸发除去。所得的油性残留物以环己烷/乙酸乙酯混合物(8/2,v/v(体积比))为洗脱剂在硅胶柱中通过色谱法提纯(产率=90%)。
制备例3
(2,3-二氢-1,4-苯并二氧杂苯-6-基)二苯基膦,化合物IVA.1
将11g化合物V与30ml无水四氢呋喃置于氩气氛围中并冷却至-78℃。滴加25.6ml的2.2M正丁基锂的二噁烷溶液,然后将反应混合物在-78℃搅拌1小时。然后滴加10.4ml氯化二苯基膦,其间温度保持在-60℃。然后将反应混合物的温度缓慢升至0℃,在0℃加入20ml饱和氯化铵溶液。然后以20ml饱和氯化钠溶液洗涤有机相两次,再在硫酸镁上干燥,过滤后将溶剂在减压下蒸发除去,以获得结晶的橙色油状物。随后以热己烷洗涤该固体,然后滤出(产率=90%)。
1H NMR(200MHz)CDCl3:4.26(4H,m);6.80-6.84(2H,m);6.85(1H;d:J=4Hz);7.32(10H,m)
31P NMR(162MHz)CDCl3:-4.66ppm
制备例4
(2,3-二氢-1,4-苯并二氧杂苯-6-基)二苯基氧化膦,化合物IIIA.1
将8ml的30%过氧化氢水溶液滴加到16.3g的化合物IVA.1溶于60ml甲醇形成的悬浮液中,反应混合物的温度保持在低于40℃。搅拌1小时后,加入14ml的30%亚硫酸钠水溶液。继续搅拌1小时,再加入9ml的1N盐酸水溶液。所得溶液在40℃下浓缩,以50ml二氯甲烷萃取出水性残留物。有机相在硫酸镁上干燥,将溶剂在减压下蒸发除去以获得结晶的黄色油状物。将所得固体以热己烷洗涤,然后滤出(定量产率)。
EI质谱:M+=335
1H NMR(200MHz)CDCl3:4.26(4H,m);6.95(1H,dd:J=11.8Hz,J=3.1Hz);7.09-7.18(2H,m);7.42-7.54(6H,m);7.61-7.72(4H,m)
31P NMR(162MHz)CDCl3:30.1ppm
制备例4之二
(2,3-二氢-1,4-苯并二氧杂苯-6-基)二苯基氧化膦,化合物IIIA.1
用约1小时以上的时间将100.0g以200ml无水THF稀释的6-溴-2,3-二氢-1,4-苯并二氧杂苯在氮气环境中加入到由12.4g镁与31ml无水THF形成的悬浮液中,温度保持在低于60℃。当反应混合物在60℃恒温2小时后,用3小时以上的时间在其中加入107.7g氯化二苯基膦,同时使反应介质中温度不超过10℃。当在20℃恒温18小时后,加入35ml甲醇。搅拌反应介质1小时,然后冷却至0℃。然后加入30ml的35%过氧化氢,反应混合物中温度不超过5℃。当在20℃恒温2小时后,在减压下蒸发除去溶剂,将所得固体物质溶于900ml热乙酸异丙酯中,然后以200ml的1N HCl、150ml的1N碳酸钾水溶液和150ml水相继洗涤三次,随后在硫酸镁上干燥。在减压下蒸发除去500ml溶剂后,将反应混合物冷却至0℃,过滤并以30ml乙酸异丙酯清洗两次。在20℃下减压干燥72小时后,得到113g乳白色固体(产率=72%)。
制备例5
(S)-[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双(二苯基氧化膦),化合物IIA.1
将30g化合物IIIA.1与600ml无水四氢呋喃经过脱气,被置于氩气环境中,然后以低温恒温器使之冷却至-100℃。在-100℃下滴加65ml的1.5M的叔丁基锂的戊烷溶液。用30分钟以上的时间使反应混合物温度升至-70℃,然后在该温度下搅拌3小时30分。在氩气流中迅速一次性加入19.8g无水三氯化铁。然后将反应混合物缓慢升至室温,并搅拌12小时。将其在60℃下浓缩,并加入50ml的1N氢氧化钠溶液和500ml的二氯甲烷。所得沉淀物经硅藻土滤出,然后以100ml二氯甲烷清洗。有机相以50ml水和50ml饱和氯化钠水溶液洗涤,然后在硫酸镁上干燥。在减压下蒸发除去溶剂后,将所得固体溶于150ml氯仿中,随后将12g的(-)-L-二苯甲酰酒石酸溶于180ml乙酸乙酯形成的溶液加入其中。数分钟后出现沉淀。将该沉淀滤出,然后在200ml二氯甲烷中制成悬浮液,再在其中加入100ml的1N氢氧化钾水溶液。在室温下搅拌该反应混合物30分钟,随后将有机相分离出来,再以50ml水和50ml饱和氯化钠水溶液洗涤,然后在硫酸镁上干燥。减压下蒸发除去溶剂(产率=50%)。
1H NMR(200MHz)CDCl3:3.42(2H,m);3.69(2H,m);3.92(2H,m);4.06(2H,m);6.65(2H,dd);6.77(dd);7.26-7.56(16H,m);7.68(4H,m)
31P NMR(162MHz)CDCl3:30.97ppm
CI质谱:MH+=671
熔点>260℃
[α]D 20(CHCl3,C=1)=-140°
化合物IIA.1与L-二苯甲酰酒石酸形成的络合物的X射线结构揭示了其为(S)绝对构型。
可采用类似的方法以制备化合物II4.2:(R)-[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双(二苯基氧化膦)
[α]D 20(CHCl3,C=1)=+143°
制备例6
(2,2-二氟-1,3-苯并间二氧杂环戊烯-5-基)二苯基氧化膦,化合物IIIA.2
用2小时以上的时间将90.1g以168ml无水THF稀释的5-溴-2,2-二氟-1,3-苯并间二氧杂环戊烯在氮气环境中加入到10.2g镁在25.2ml无水THF中形成的悬浮液中,其间温度保持在60℃。当反应混合物在室温恒温3小时后,用2小时以上的时间在其中加入90g氯化二苯基膦,并使反应混合物中温度不超过20℃。当反应混合物在20℃恒温19小时后,将其用27ml水和135ml 1N的HCl水解,然后经由270ml乙酸乙酯萃取。在倾析与相分离后,有机相以135ml 1N的HCl、135ml饱和碳酸氢钾水溶液以及135ml水依次洗涤,然后在硫酸镁上干燥。减压下蒸发除去溶剂,获得128g褐色粘性油状物。该油状物以乙酸乙酯/庚烷混合物(比值范围50/50-100/0,v/v)作为洗脱剂经由二氧化硅过滤提纯(褐色油状物,90g,产率=66%)。
CI质谱:MH+=359
1H NMR(300MHz)CDCl3:7.70-7.41(11H,m);7.37(1H,dd);7.16(1H,dd)
制备例7
(2,2-二氟-4-碘-1,3-苯并间二氧杂环戊烯-5-基)二苯基氧化膦,化合物IIIC.1
在0℃氮气环境中用40分钟以上的时间将96.6ml的2.5M丁基锂的己烷溶液加入到35.5ml二异丙胺稀释于150ml无水THF形成的溶液中。在0℃下搅拌15分钟后,在-78℃氮气环境中用1小时以上的时间将该溶液缓慢地加入到82.5g化合物IIIA.2稀释于600ml无水THF形成的溶液中,然后在-78℃保持搅拌50分钟。将60.9g碘稀释于250ml无水THF中形成的溶液在-78℃下用1小时以上的时间加入到前述溶液中。然后反应混合物缓慢升温至室温,随后搅拌20小时。然后再冷却至0℃,过滤,将所得固体以20ml THF清洗三次。在40℃下减压干燥5小时后,得到97.6g乳白色固体(产率=87.5%)。
EI质谱:M+=484
1H NMR(250MHz)CDCl3:7.73-7.48(10H,m);7.04-6.96(2H,m)
制备例8
(R,S)-[4,4’-双(2,2-二氟-1,3-苯并间二氧杂环戊烯)-5,5’-二基]双(二苯基氧化膦),外消旋化合物IIA.3
将30g化合物IIIC.1、11.8g铜粉以及150mlDMF在130℃下加热4小时。随后反应混合物冷却至室温,将其过滤,然后浓缩。随后将所得褐色油状物以300ml二氯甲烷稀释,然后以100ml饱和氯化铵水溶液和100ml水依次洗涤,再在硫酸镁上干燥。所得的黄色固体在0℃下从250ml甲醇中重结晶,然后减压干燥获得15.2g白色固体(产率=68.7%)。
CI质谱:M+=715
1H NMR(300MHz)CDCl3:7.66-7.25(20H,m);7.03-7.00(4H,m)
然后在市售商标名为ChiroseC3的手性相柱上通过色谱法拆分化合物IIA.3,以获得光学纯的(S)和(R)对映异构体。
制备例9
二苯基(2,3-二氢-1,4-苯并二氧杂苯-6-基)膦酸酯(化合物IIIB.1)
将602mg(25.6mM)活性镁与1ml无水四氢呋喃(THF)在氩气环境中装入一个三颈圆底烧瓶中。加入两滴1,3-二溴丙烷,然后加入5g(23.3mM)化合物V溶于10ml THF形成的溶液,其间温度保持在0℃。在室温下搅拌反应混合物2小时,然后在溶剂的回流温度下搅拌1小时。将所形成的镁化合物缓慢地加入到预先冷却至-5℃的由4.84ml(23.25mM)二苯基次膦酰氯溶于5ml THF而形成的溶液中。室温下将该溶液搅拌过夜,然后减压浓缩。残留物由20ml乙酸乙酯提取,再与10ml当量盐酸溶液一起搅拌30分钟。水相以乙酸乙酯萃取,合并的有机相以水洗涤,在硫酸镁上干燥,然后减压浓缩。所得的油状物以环己烷/乙酸乙酯混合物(7/3,v/v)为洗脱剂经由硅胶色谱法提纯,从而获得5g略带粉红色、白色固体状的目标产物(产率=59%)。
1H NMR(200MHz,CDCl3):δ=4.25-4.32(m,4H);6.95(dd,J=5.1,8.1Hz,1H);7.10-7.35(m,10H);7.39-7.43(m,1H);7.47(ddd,1H)
13C NMR(50MHz,CDCl3):δ=64.1;64.5;117.7(d,J=18.5Hz);120.5(d,J=4.5Hz);121.6(d,J=12.7Hz);124.9;125.9(d,J=10.6Hz);129.6;143.5(d,J=22.2Hz);147.9;150.5(d,J=7.4Hz)
31P NMR(162MHz,CDCl3):δ=13.11
质谱(EI):M+=368
制备例10
二乙基(2,3-二氢-1,4-苯并二氧杂苯-6-基)膦酸酯(化合物IIIB.2)
将20g(92.SmM)根据制备例1获得的化合物和1.2g(9.28mM)氯化镍置于一配备有蒸馏装置的圆底烧瓶中。搅拌混合物,升温至160℃,然后滴加18.8ml(111.4mM)亚磷酸三乙酯。滴加结束后将反应混合物在160℃搅拌1小时,同时通过蒸馏收集反应形成的溴乙烷。然后将反应介质冷却,加入50ml***和50ml乙酸乙酯。过滤所得悬浮液,将滤出液减压浓缩。随后残留物以乙酸乙酯作为洗脱剂经由硅胶色谱法提纯,从而获得25g无色油状的目标产物(定量产率)。
1H NMR(400MHz,CDCl3):δ=1.24(t,J=7.0Hz,6H);4.01(qd,J=7.0,9.9Hz,4H);4.20-4.23(m,4H);6.86(dd,J=8.1,4.6Hz,1H);7.19-7.22(m,2H)
13C NMR(50MHz,CDCl3):δ=16.1;61.8;64.0;64.4;117.5(d,J=17.5Hz);120.9(d,J=12.0Hz);125.3(d,J=10.0Hz);125.5;143.4(d,J=20.8Hz);147.2
31P NMR(162MHz,CDCl3):δ=20.20
质谱(EI):M+=272
制备例11
四苯基[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]二膦酸酯(化合物IIB.1)
制备0.675ml(3.97mM)的四甲基哌啶溶于5ml THF形成的溶液,然后将其冷却至-78℃,并在其中加入1.32ml(3.24mM)2.4M的正丁基锂的己烷溶液。在-15℃搅拌该溶液30分钟,再将该溶液加入到冷却至-78℃的1g(2.27mM)化合物IIIB.1溶于5mlTHF而形成的溶液中。将该混合物在-78℃下搅拌1小时,然后加入570mg(3.5mM)无水三氯化铁。室温下搅拌该混合物过夜,然后减压浓缩。残留物用30ml二氯甲烷提取,然后在15ml的1N氢氧化钠溶液存在下搅拌30分钟。将混合物过滤,分离出有机相,以15ml水、15ml的1N盐酸溶液、10ml水和10ml饱和氯化钠溶液依次洗涤。然后将该有机相在硫酸镁上干燥,然后减压浓缩。残留物以环己烷/乙酸乙酯混合物(1/1,v/v)作为洗脱剂经由硅胶色谱法提纯,从而获得200mg淡黄色固体状的目标产物(产率=20%)。
1H NMR(200MHz,CDCl3):δ=3.80-3.90(m,2H);3.95-4.01(m,4H);4.14-4.30(m,2H);6.88(dd,J=8.2,17.7Hz,8H);7.00-7.22(m,14H);7.72(dd,J=14.5,8.4Hz,2H)
13C NMR(50MHz,CDCl3):δ=63.8;64.2;116.8(d,J=18.5Hz);120.8;124.5;126.9(d,J=9.8Hz);129.2;142.3(d,J=22.1Hz);147.6;150.5(d,J=8.1Hz)
31P NMR(162MHz,CDCl3):δ=11.68
质谱(CI):(M+H)+=735
制备例12
四乙基[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]二膦酸酯(化合物IIB.2)
制备由6.72ml(44.4mM)的TMEDA(四甲基乙二胺)与5g(18.5mM)化合物IIIB.2溶于50ml THF而形成的溶液,在-60℃下在其中加入20.2ml(22.2mM)1.1M仲丁基锂的己烷溶液。在-60℃下搅拌该溶液2小时,然后在-60℃下在其中迅速一次性加入3.91g(24mM)无水三氯化铁。在室温下搅拌该混合物过夜。然后减压浓缩,以100ml二氯甲烷和30ml 1N氢氧化钠溶液提取,搅拌该悬浮液30分钟。过滤后,以水洗涤有机相,然后以30ml的1N盐酸溶液、30ml水和30ml饱和氯化钠溶液依次洗涤,再在硫酸镁上干燥,过滤后减压浓缩。将固体残留物结晶(乙酸乙酯/己烷,1∶1)以获得1.6g白色固体状的目标化合物(产率=32%)。
1H NMR(400MHz,CDCl3):δ=1.13(q,J=7.0Hz,12H);3.69-3.80(m,2H);3.85-3.92(m,6H);4.14-4.17(m,4H);4.22-4.24(m,4H);6.90(dd,J=4.0,8.3Hz,2H);7.41(dd,J=13.8,8.5Hz,2H)
13C NMR(50MHz,CDCl3):δ=16.1;61.2(d,J=8.0Hz);63.9;64.2;116.2(d,J=17.3Hz);125.2;125.9(d,J=9.1Hz);128.8(d,J=12.1Hz);141.8(d,J=20.8Hz);146.5
31P NMR(162MHz,CDCl3):δ=19.13
质谱(EI):M+=542
制备例13
[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]二膦酰四氯(化合物IIC)
将2g(3.69mM)化合物IIB.2、16ml亚硫酰氯以及0.4ml二甲基甲酰胺在氩气氛中引入配备有冷凝器的圆底烧瓶中,并回流(80-90℃)4.5小时。溶液变成亮黄色。减压浓缩该混合物,干燥以制得一种暗橙色固体(针状),在下一步骤中直接使用前,将该产物在氩气氛下保存于冰箱里。
1H NMR(400MHz,CDCl3):δ=4.17-4.36(m,8H);7.06(dd,J=8.7,5.8Hz,2H);7.54(dd,J=20.0,8.7Hz,2H)
31P NMR(162MHz,CDCl3):δ=34.74
制备例14
[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双[二(4-甲基苯基)氧化膦],化合物IIA.4
将19.9ml(36.9mM)1.85M的正丁基锂的己烷溶液于-78℃下加入到由6.3g(36.9mM)的4-溴代甲苯溶于50mlTHF而形成之溶液中。出现白色悬浮液。将该溶液在-78℃下搅拌1小时,然后加入到由1.86g(3.69mM)化合物IIC溶于10mlTHF而形成之溶液中。溶液变成暗褐色。随后将该混合物升温至室温,然后在50℃搅拌1小时。加入20ml饱和氯化铵溶液,然后先以水再以饱和氯化钠溶液洗涤有机相,再在硫酸镁上干燥,然后减压浓缩。残留物以乙酸乙酯/甲醇混合物(9/1,v/v)作为洗脱剂经由硅胶色谱法提纯,从而获得1.32g米黄色固体状的目标产物(两步骤产率=50%)。
1H NMR(400MHz,CDCl3):δ=2.30(s,6H);2.38(s,6H);3.57(ddd,J=2.3,7.2,11.4Hz,2H);3.75(ddd,J=2.4,4.3,11.6Hz,2H);3.97(ddd,J=2.3,4.2,11.2Hz,2H);4.09(ddd,J=2.6,7.2,11.1Hz,2H);6.65(dd,J=8.5,13.2Hz,2H);6.74(dd,J=3.0,8.4Hz,2H);7.04(dd,J=2.4,8.0Hz,4H);7.20(dd,J=2.1,8.0Hz,4H);7.32(dd,J=8.0,11.8Hz,4H);7.53(dd,J=8.0,11.4Hz,4H)
13C NMR(50MHz,CDCl3):δ=21.4;63.4;64.0;115.8;126.5(d,J=13.3Hz);128.4(d,J=12.3Hz);132.1(d,J=10.4Hz);132.4;132.9;135.8;140.9;142.5;145.7
31P NMR(162MHz,CDCl3):δ=30.95
质谱(CI):(M+H)+=727
制备例15
[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双[二(3,5-二甲基苯基)氧化膦],化合物IIA.5
通过与制备例13相类似的程序以5-溴-间二甲苯为起始原料制得该化合物。
1H NMR(400MHz,CDCl3):δ=2.12(s,12H);2.31(s,12H);3.63-3.66(m,2H);3.75-3.79(m,2H);4.00-4.04(m,2H);4.08-4.13(m,2H);6.72-6.75(m,4H);6.96(s,2H);7.11(d,J=12.7Hz,6H);7.29(d,J=12.0Hz,4H)
13C NMR(50MHz,CDCl3):δ=21.0;21.3;63.4;63.9;115.9(d,J=15.4Hz);126.6(d,J=12.9Hz);129.8;132.5;134.1;136.1;137.1;141.0(d,J=14.9Hz);145.5
31P NMR(162MHz,CDCl3):δ=31.78
质谱(CI):(M+H)+=783
实施例1
(S)-[5,5’-双(2,3--二氢-1,4-苯并二氧杂苯)-6,6’-二基]双(二苯基膦),化合物I.1
在氩气环境下将2.12ml三丁基胺以及780μl三氯硅烷先后加入到500mg化合物IIA.1以及5ml经脱气蒸馏的二甲苯中。将反应混合物在140℃加热12小时。当其降至室温时,在其中加入5ml 4N氢氧化钠水溶液。然后在室温下搅拌该反应混合物30分钟,在其中加入15ml二氯甲烷。以5ml蒸馏水以及5ml饱和氯化钠水溶液先后洗涤有机相,随后减压浓缩。其后加入10ml甲醇,在氩气环境下滤出所得白色沉淀物,然后以10ml甲醇洗涤,减压干燥4小时(产率=91%)。
[α]D 20(苯,C=0.1)=-44°
下列化合物可用同样方法制备:
(R)-[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双(二苯基膦),化合物I.2
1H NMR(200MHz,CDCl3):3.35(2H,m);3.83(4H,m);4.13(2H,m);6.62(2H,dd,J=8Hz,J=3Hz);6.85(2H,d:J=8Hz);7.09(4H,m);7.23(8H,m);7.31(8H,m)
31P NMR(162MHz,CDCl3):-14.3ppm
[α]D 20(苯,C=0.1)=+44°
(R)-[4,4’-双(2,2-二氟-1,3-苯并间二氧杂环戊烯)-5,5’-二基]双(二苯基膦),化合物I.3
[α]D 20(甲醇,C=0.5)=+48°
(S)-[4,4’-双(2,2-二氟-1,3-苯并间二氧杂环戊烯)-5,5’-二基]双(二苯基膦),化合物I.4
[α]D 20(甲醇,C=0.5)=-49°
[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双[二(4-甲基苯基)膦],化合物I.5
1H NMR(200MHz,CDCl3):δ=2.29(s,6H);2.33(s,6H);3.32-3.44(m,2H);3.74-3.94(m,4H);4.03-4.18(m,2H);6.62(m,2H);6.82(d,J=8.4Hz,2H);6.87-7.23(m,16H)
[5,5’-双(2,3-二氢-1,4-苯并二氧杂苯)-6,6’-二基]双[二(3,5-二甲基苯基)膦],化合物I.6
1H NMR(400MHz,CDCl3):δ=2.12(s,12H);2.25(s,12H);3.47(ddd,J=2.3,4.3,12.0Hz,2H);3.83(ddd,J=2.1,6.9,11.6Hz,2H);3.95(ddd,J=2.2,4.5,11.4Hz,2H);4.14(ddd,J=2.3,7.2,11.2Hz,2H);6.63-6.67(m,6H);6.80(m,4H);6.90(d,J=8.1Hz,6H)
31P NMR(162MHz,CDCl3):δ=-14.52
实施例2
化合物VII.1:络合物[Ru2Cl5L2]-[(C2H5)NH2]+,其中L=化合物I.1
将由50mg双(苯二氯化钌)、128mg化合物1.1以及21.6mg二乙胺盐酸盐溶于10ml四氢呋喃而形成的溶液回流16小时。然后减压蒸发除去溶剂。将所得固体减压干燥。
31P NMR(162MHz)CDCl3:51.1(d);54.4(d)J=38Hz
实施例3
化合物VI.1:络合物[LRuCl2(吡啶)2],其中L=化合物I.2
将42.2mg的(降冰片二烯)RuCl2(吡啶)2、63.9mg化合物1.2以及15ml经脱气的无水CH2Cl2加入,反应混合物在室温下氩气环境中搅拌12小时。减压浓缩和干燥该溶液,以获得96mg橙黄色固体。
31P NMR(162MHz)CDCl3:40.9ppm
实施例4
化合物VI.2:络合物[LRuCl2S-DPED],其中L=化合物I.2
将34mg实施例3中所得的[LRuCl2(吡啶)2]、7.4mg(S,S)-二苯基乙二胺以及5ml经脱气的无水CH2Cl2在室温下氩气环境中搅拌2小时。减压浓缩和干燥该溶液,以获得96mg橙黄色固体。
31P NMR(162MHz)CDCl3:48.1ppm
实施例5
化合物VII.2:络合物[LRhcod]+BF4 -,其中L=化合物I.2
将50mg[Rhcod]+BF4 -和58.6mg化合物I.2置于一舒伦克(Schlenk)试管中。通过三次连续的真空/氩气换气将该体系置于氩气环境中。然后在其中加入10mlTHF,搅拌反应混合物30分钟。将溶剂蒸发除去之后,所得残留物在真空下干燥,获得110mg黄色粉末。
实施例6
不对称性氢化反应
通用方法:
a)采用就地制备的式[LRuBr2]手性钌催化剂,其中L=化合物(I)
将2.2当量的0.16N-0.19N氢溴酸的甲醇溶液在氩气环境中滴加到由3.2mg(1,5-环辛二烯)二甲基烯丙基钌和1.1当量的化合物(I)溶于1ml丙酮而形成的溶液中。在室温下搅拌30分钟后,将溶剂减压蒸发除去。
然后将需氢化的底物(1mmol)溶于2ml氢化溶剂(醇或卤化型的,例如二氯甲烷)中,然后在所需氢化压力和所需氢化温度并存在所述催化剂的条件下将该底物溶液置于一高压反应釜中。
b)采用三氯化钌
将需氢化的底物(1mmol)溶于2ml氢化溶剂中,然后将其加入到2.1mg三氯化钉和1.1当量的化合物(I)中。在一高压反应釜中,在所需的压力和温度下及必要的时间内完成所述氢化反应。
c)采用实施例2所描述的络合物
将需氢化的底物(1mmol)溶于2ml氢化溶剂中,然后将其加入到3.6mg络合物中。在一高压反应釜中,在所需的压力和温度下及必要的时间内完成所述氢化反应。
本发明的用于立体选择性氢化反应的催化剂可用于进行如下类型的还原反应:
[Ru]=[LRuBr2],其中L=化合物I.2
[Ru] | ee(%)(构型) |
[LRuBr2]就地制备 | 98.5(R) |
化合物VII.1*:[Ru2Cl5L2]-[(C2H5)NH2]+ | 98.2(R) |
*其中L=化合物I.2
S/C代表底物/催化剂重量比
下表1以实施例的形式显示了不同底物的氢化反应所得的对映体过量百分数(ee),所采用的反应条件未经优化([Ru]一栏中的字母指的是制备该催化剂的方法)。
表1
表1(续)
实施例7
不对称性1,4-加成反应
在氩气环境下将1ml二噁烷、0.1ml蒸馏水以及0.4mmol环己酮加入到3.1mg Rh(acac)(C2H4)2、0.012mmol化合物I.1以及2mmol苯基硼酸中。在100℃下加热该反应混合物5小时。当其降至室温后,减压蒸馏除去溶剂。所得的残留物溶于20ml乙酸乙酯中,然后以5ml饱和碳酸氢钠水溶液洗涤,再在硫酸钠上干燥。然后减压蒸馏除去溶剂。所得产品在硅石上过滤以分离(S)-3-苯基环己酮,该产物以下列1H NMR谱表征。
1H NMR(200MHz)CDCl3:1.84(2H,m);2.16(2H,m);2.46(4H,m);3.0(1H,m);7.21-7.45(5H,m)
对映体过量:96%ee(由Lipodex A手性GPC测定)
实施例8
在相同的反应操作条件(温度、压力和溶剂)下分别将本发明的钌络合物和Ru-Binap型络合物用于各种底物的氢化反应,下表2对所得结果进行了比较。
表2还比较了表1中由本发明的络合物得到的结果与所述络合物中由BINAP配体替代所述配体(I)而形成的相应络合物得到的结果。
表2
表2(续)
Claims (19)
1.光学纯型或外消旋型的式(I)化合物:
其中:
-R1与R2各自独立地是:
-(C5-C7)环烷基;选择地具有以下一个或一个以上的取代基的苯基:(C1-C4)烷基、(C1-C4)烷氧基或双(C1-C4)烷基氨基;或者是具有卤素原子作为取代基的苯基,或
-5元杂芳基;而且
-A为亚乙基或CF2基团。
2.如权利要求1所述的式(I)化合物,其特征在于R1与R2是相同的。
3.如权利要求2所述的式(I)化合物,其特征在于R1与R2是苯基。
5.用于制备权利要求1中式(I)化合物的式(IIB)中间体:
其中A如式(I)所定义,R为(C1-C4)烷基或选择性地具有取代基的苯基。
8.用于制备权利要求1中式(I)化合物的式(IVA)中间体:
其中R1、R2与A如权利要求1中式(I)所定义。
9.如权利要求1-3任意一项所述的式(I)化合物在制备金属络合物时作为配体的用途,所述金属络合物在不对称性催化中用作手性催化剂。
10.手性的金属催化剂,其特征在于它含有至少一个如下所述的配体:所述配体选自如权利要求1-3任意一项所述的式(I)化合物。
11.如权利要求10所述的手性的金属催化剂,其特征在于所述选自如权利要求1-3任意一项所述的式(I)化合物的配体是光学纯型的。
12.如权利要求10或11所述的手性的金属催化剂,其特征在于所述金属选自铑、钌、铱、钯、铜或镍。
13.如权利要求12所述的手性的金属催化剂,该手性的金属催化剂由式(VI)表示:
MmLnXpSq (VI),
其中:
-M为选自铑、钌、铱、钯和镍的一种金属;
-L为如权利要求1-3中任一项所述的式(I)化合物;而且
-X、S、m、n、p和q定义如下:
·若M=Rh,则X=C1、Br或I;m=n=p=2;q=0;
·若M=Ru,则:X=-OC(O)CH3;m=n=1;p=2;q=0;
或 X=Br;m=n=1;p=2;q=0;
或 X=Cl;S=N(CH2CH3)3;m=n=2;p=4;q=1;
或 X=甲代烯丙基;m=n=1;p=2;q=0;
或 X=Cl;S=吡啶;m=n=1;p=q=2;
或 X=Cl;S=手性1,2-二胺;m=n=1;p=q=2或p=2,
q=1;
·若M=Ir,则X=Cl、Br或I;m=n=p=2;q=0;
·若M=Pd,则:X=Cl;m=n=1;p=2;q=0;
或 X=π-烯丙基;m=n=p=2;q=0;
·若M=Ni,则X=Cl、Br或I;m=n=1;p=2;q=0。
14.如权利要求12所述的手性的金属催化剂,该手性的金属催化剂由式(VII)表示:
[MrLsZtWu]Yv(VII),
其中:
-M为选自铑、钌、铱、钯和铜的一种金属;
-L为如权利要求1-3中任一项所述的式(I)化合物;而且
-Z、W、r、s、t、u和v定义如下:
·若M=Rh,则Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6、OTf或BPh4;r=s=t=v=1;u=0;
·若M=Ru,则:Z=Cl、Br或I;W=苯或对甲基异丙基苯;Y=Cl、
Br或I;r=s=t=u=v=1;
或 Y=BF4、ClO4、PF6或BPh4;r=s=1;t=u=0;v=2;
或 Z=Cl;Y=NH2(C2H5)2;r=s=2;t=5;u=0;v=1;
·若M=Ir,则Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6
或BPh4;r=s=v=1;t=1;u=0;
·若M=Pd,则Y=BF4、ClO4、PF6或BPh4;r=s=v=1;t=u=0;
·若M=Cu,则Y=PF6或ClO4;r=s=v=1;t=u=0。
15.如权利要求13所述的式(VI)催化剂,其特征在于其中M=Ru以及
·X=Br;m=n=1;p=2;q=0;
·或X=Cl;S=N(CH2CH3)3;m=n=1;p=4;q=1;
·或X=Cl;S=吡啶;m=n=1;p=q=2。
16.如权利要求14所述的式(VII)催化剂,其特征在于其中M=Rh并且Z=1,5-环辛二烯或降冰片二烯;Y=BF4、ClO4、PF6、OTf或BPh4;r=s=t=v=1;u=0。
17.催化氢化反应方法,其特征在于所述方法使用了如权利要求10-16任一项所述的催化剂。
18.如权利要求10-16任一项所述的金属催化剂在催化不对称性反应中的用途。
19.如权利要求18所述的用途,其中,所述不对称反应是氢化反应和C-C键的形成反应。
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US5872273A (en) * | 1996-12-26 | 1999-02-16 | Takasago International Corporation | Chiral diphosphine compound intermediate for preparing the same transition metal complex having the same diphosphine compound as ligand and asymmetric hydrogenation catalyst |
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CA2462045A1 (en) | 2003-04-10 |
KR100876718B1 (ko) | 2008-12-31 |
EP1436304B1 (fr) | 2005-03-09 |
FR2830254B1 (fr) | 2004-09-17 |
WO2003029259A1 (fr) | 2003-04-10 |
CN1558908A (zh) | 2004-12-29 |
JP2005504129A (ja) | 2005-02-10 |
CA2462045C (en) | 2011-08-16 |
FR2830254A1 (fr) | 2003-04-04 |
PT1436304E (pt) | 2005-07-29 |
US6878665B2 (en) | 2005-04-12 |
PL208407B1 (pl) | 2011-04-29 |
EP1436304A1 (fr) | 2004-07-14 |
US20040260101A1 (en) | 2004-12-23 |
ES2238635T3 (es) | 2005-09-01 |
NO20041234L (no) | 2004-03-24 |
KR20040041607A (ko) | 2004-05-17 |
ATE290540T1 (de) | 2005-03-15 |
DE60203193T2 (de) | 2006-01-26 |
PL368527A1 (en) | 2005-04-04 |
MXPA04002943A (es) | 2004-11-22 |
BR0212763B1 (pt) | 2012-12-25 |
BR0212763A (pt) | 2004-10-13 |
JP4342942B2 (ja) | 2009-10-14 |
DE60203193D1 (de) | 2005-04-14 |
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