WO2016056669A1 - 固相担持ルテニウム-ジアミン錯体及び光学活性化合物の製造方法 - Google Patents
固相担持ルテニウム-ジアミン錯体及び光学活性化合物の製造方法 Download PDFInfo
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- WO2016056669A1 WO2016056669A1 PCT/JP2015/078923 JP2015078923W WO2016056669A1 WO 2016056669 A1 WO2016056669 A1 WO 2016056669A1 JP 2015078923 W JP2015078923 W JP 2015078923W WO 2016056669 A1 WO2016056669 A1 WO 2016056669A1
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- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- BMRWNKZVCUKKSR-UHFFFAOYSA-N butane-1,2-diol Chemical compound CCC(O)CO BMRWNKZVCUKKSR-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- QCRFMSUKWRQZEM-UHFFFAOYSA-N cycloheptanol Chemical compound OC1CCCCCC1 QCRFMSUKWRQZEM-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- FHADSMKORVFYOS-UHFFFAOYSA-N cyclooctanol Chemical compound OC1CCCCCCC1 FHADSMKORVFYOS-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 150000001975 deuterium Chemical group 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- MCVFFRWZNYZUIJ-UHFFFAOYSA-M lithium;trifluoromethanesulfonate Chemical compound [Li+].[O-]S(=O)(=O)C(F)(F)F MCVFFRWZNYZUIJ-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- QNVRIHYSUZMSGM-UHFFFAOYSA-N n-butyl methyl carbinol Natural products CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N n-butyl methyl ketone Natural products CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- WOFPPJOZXUTRAU-UHFFFAOYSA-N octan-4-ol Chemical compound CCCCC(O)CCC WOFPPJOZXUTRAU-UHFFFAOYSA-N 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- WYRXRHOISWEUST-UHFFFAOYSA-K ruthenium(3+);tribromide Chemical compound [Br-].[Br-].[Br-].[Ru+3] WYRXRHOISWEUST-UHFFFAOYSA-K 0.000 description 1
- LJZVDOUZSMHXJH-UHFFFAOYSA-K ruthenium(3+);triiodide Chemical compound [Ru+3].[I-].[I-].[I-] LJZVDOUZSMHXJH-UHFFFAOYSA-K 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- RHUVFRWZKMEWNS-UHFFFAOYSA-M silver thiocyanate Chemical compound [Ag+].[S-]C#N RHUVFRWZKMEWNS-UHFFFAOYSA-M 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- PZJJKWKADRNWSW-UHFFFAOYSA-N trimethoxysilicon Chemical group CO[Si](OC)OC PZJJKWKADRNWSW-UHFFFAOYSA-N 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
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- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/1616—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts
- B01J31/1625—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups
- B01J31/1633—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups covalent linkages via silicon containing groups
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/165—Polymer immobilised coordination complexes, e.g. organometallic complexes
- B01J31/1658—Polymer immobilised coordination complexes, e.g. organometallic complexes immobilised by covalent linkages, i.e. pendant complexes with optional linking groups, e.g. on Wang or Merrifield resins
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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
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—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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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—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
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
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- 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
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
- B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
- B01J21/08—Silica
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
- B01J2531/0258—Flexible ligands, e.g. mainly sp3-carbon framework as exemplified by the "tedicyp" ligand, i.e. cis-cis-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane
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- B01J2531/82—Metals of the platinum group
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- B01J2540/34—Sulfonyl groups
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- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
- C07C209/52—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of imines or imino-ethers
Definitions
- the present invention relates to a novel ruthenium-diamine complex supported on a solid phase, and a method for selectively producing optically active alcohols and optically active amines that are important as precursors for the synthesis of pharmaceuticals and functional materials using them as catalysts. About.
- the present inventors have prepared an aromatic compound moiety (including an arene moiety) coordinated to a ruthenium complex having an optically active diamine (hereinafter referred to as “arene compound moiety” in the present specification.
- Industrial use that has high catalytic activity, good asymmetric yield, and simple production method by supporting a complex having a chain moiety that links the diamine moiety and a diamine moiety on a solid support.
- the present inventors have found that a ruthenium-diamine complex supported on a solid phase suitable for the above can be obtained, and the present invention has been completed. That is, the present invention includes the following contents.
- a solid-supported ruthenium complex represented by the general formula (1).
- R 2 and R 3 each independently represents a substituent selected from an alkyl group having 1 to 10 carbon atoms; an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, and a halogen atom.
- R 2 and R 3 may be combined to form a ring.
- R 11 , R 12 , R 13 , R 14 , and R 15 each independently represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an alkoxy group having 1 to 10 carbon atoms.
- R 16 , R 17 , R 18 , and R 19 each independently represent a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 10 carbon atoms, or an alkoxy group having 1 to 10 carbon atoms.
- R 16 and R 17 may form a carbonyl group with R 16 and R 17 and the carbon atom to which they are bonded.
- R 18 and R 19 may form a carbonyl group with R 18 and R 19 and the carbon atom to which they are bonded.
- Z represents an oxygen atom or methylene (—CH 2 —).
- n 1 represents 1 or 2
- n 2 represents an integer of 1 to 3.
- Y represents a hydrogen atom.
- X represents a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, a benzenesulfonyloxy group, a hydrogen atom, or a halogen atom.
- j and k each independently represent 0 or 1, but j + k never becomes 1.
- A is a linear or branched alkylene group having 1 to 20 carbon atoms which may have a substituent, a cycloalkylene group having 3 to 20 carbon atoms which may have a substituent, or a substituent.
- B is (Wherein Rd and Re each independently represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an alkoxy group having 1 to 10 carbon atoms), (Wherein Rf represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms), An oxygen atom or a sulfur atom is represented. Note that any of the coupling portions of the formulas (B1), (B2), and (B3) may be on the D side. D represents a solid phase carrier. p and q each independently represents 0 or 1. )
- a solid-supported ruthenium complex represented by the general formula (2) (In the formula, * represents an asymmetric carbon atom.
- R 2, R 3, R 11 , R 12, R 13, R 14, R 15, R 16, R 17, R 18, R 19, Z, n 1, n 2, Y, A, B, D, p , And q are as defined above, and Q ⁇ represents a counter anion.
- a solid-supported ruthenium complex represented by the general formula (3) (In the formula, * represents an asymmetric carbon atom.
- R 2, R 3, R 11 , R 12, R 13, R 14, R 15, R 16, R 17, R 18, R 19, Z, n 1, n 2, Y, A, B, D, p And q are as defined above, and V represents a halogen atom.
- a method for producing a reduction product comprising reducing an organic compound in the presence of a solid-supported ruthenium complex represented by any one of the general formulas (1) to (3) and a hydrogen donor.
- a method for producing an optically active alcohol comprising reducing a carbonyl group of a carbonyl compound in the presence of a solid-supported ruthenium complex represented by any one of the general formulas (1) to (3) and a hydrogen donor.
- a method for producing an optically active amine comprising reducing an imino group of an imine compound in the presence of a solid-supported ruthenium complex represented by any one of the general formulas (1) to (3) and a hydrogen donor.
- any one of the above production methods wherein the hydrogen donor is selected from formic acid, alkali metal formate and alcohol having a hydrogen atom at the ⁇ -position carbon atom of the hydroxyl group-substituted carbon. Any one of the above production methods wherein the hydrogen donor is hydrogen.
- a reduction catalyst comprising a solid-supported ruthenium complex represented by any one of the general formulas (1) to (3). The catalyst as described above, wherein the reduction catalyst is an asymmetric reduction catalyst.
- the present invention provides a novel complex in which a ruthenium-diamine complex having a chain portion that links an aromatic compound site coordinated to ruthenium and a diamine portion is supported on a solid phase carrier.
- the ruthenium-diamine complex supported on the solid phase of the present invention has a very strong catalytic activity and can be used for the reduction of carbonyl groups or imino groups and is useful not only as various hydrogenation catalysts,
- the complex of the present invention in which the ligand is an optically active substance is excellent in stereoselectivity and gives a high asymmetric yield. Furthermore, since it is insoluble, it can be easily separated and recovered from the reaction system.
- the catalyst activity is higher than that of the conventional complex, and the catalyst activity hardly decreases even when the reuse is repeated. Furthermore, it is useful not only because the catalyst can be recovered and reused, but also because the catalyst can be filtered and removed after the reaction, so that the metal remaining in the solution after the reaction, that is, the product can be greatly reduced. Is excellent.
- optically active alcohols and optically active amines useful as raw materials for producing pharmaceuticals and functional materials can be selectively produced.
- the aromatic compound site is coordinated to the ruthenium atom, and one nitrogen atom of the diamine moiety is connected via the chain moiety. And the other nitrogen atom of the diamine moiety has a sulfonyl group, and the end of the side chain extending from the sulfonyl group is bonded to the solid phase carrier.
- two nitrogen atoms of the diamine ligand are bonded to the ruthenium atom by a covalent bond or a coordinate bond, and bonded to the diamine.
- the * mark in the general formulas (1), (2), and (3) indicates that the carbon atom marked with the * mark may be an asymmetric carbon atom.
- the carbon atom is an asymmetric carbon atom, it may be an optically active substance thereof, a mixture of optically active substances, or a racemic body (including a racemic compound).
- the Ru—X bond in the solid-supported ruthenium complex represented by the general formula (1) is an ion bond of Ru + -Q ⁇ . It is a complex.
- the solid-supported ruthenium complex represented by the general formula (3) is a dimer (dimer) via a halogen atom V, and is a complex in which an aromatic compound site is coordinated to a ruthenium atom.
- the solid-supported ruthenium complex represented by the general formula (3) is not only useful as an intermediate in producing the solid-supported ruthenium complex represented by the general formula (1) or (2), but as such Is also a complex having activity as a reduction catalyst.
- R 2 and R 3 in the general formula (1) of the present invention are each independently an alkyl group having 1 to 10 carbon atoms; an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, and a halogen atom.
- R 2 and R 3 may be combined to form a ring.
- both R 2 and R 3 are an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, and a phenyl group which may have a substituent selected from a halogen atom.
- both R 2 and R 3 are more preferably phenyl groups having no substituent.
- the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 in the general formula (1) of the present invention is a linear or branched alkyl group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms. Can be mentioned.
- alkyl group examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, an n-pentyl group, and an n-hexyl group.
- the alkyl group is preferably a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, or n-pentyl group.
- the alkyl group having 1 to 10 carbon atoms, the alkoxy group having 1 to 10 carbon atoms, and the substituent that the phenyl group may have represented by R 2 and R 3 in the general formula (1) of the present invention, and The halogen atom will be described.
- the phenyl group may have one or more substituents.
- the alkyl group having 1 to 10 carbon atoms as a substituent can be selected, for example, from the groups defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 in the above formula (1).
- Examples of the alkoxy group having 1 to 10 carbon atoms as a substituent include linear or branched alkoxy groups having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms.
- alkoxy group examples include methoxy Group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, n-pentyloxy group, n-hexyloxy group, n-heptyloxy group, Examples include an n-octyloxy group, an n-nonyloxy group, and an n-decyloxy group.
- the alkoxy group is preferably a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, an s-butoxy group, a t-butoxy group, or an n-pentyloxy group.
- a halogen atom as a substituent, a fluorine atom, a chlorine atom, and a bromine atom are mentioned, for example.
- the cycloalkyl group having 3 to 8 carbon atoms represented by R 2 and R 3 in the general formula (1) of the present invention is a monocyclic or condensed cyclic group having 3 to 8 carbon atoms, preferably 5 to 8 carbon atoms. Or a cross-linked cycloalkyl group, and specific examples include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.
- the alkyl group having 1 to 10 carbon atoms as the substituent which the cycloalkyl group represented by R 2 and R 3 in the formula (1) may have is represented by, for example, R 2 and R 3 in the above formula (1).
- the cycloalkyl group can have one or more substituents.
- cycloalkane ring examples include a cyclopentane ring, a cyclohexane ring, and a cycloheptane ring, and these rings may have a substituent selected from an alkyl group having 1 to 10 carbon atoms.
- substituents include a methyl group, an isopropyl group, and a t-butyl group.
- the ring can have one or more substituents.
- R 11 , R 12 , R 13 , R 14 , and R 15 are each independently a hydrogen atom, an alkyl having 1 to 10 carbon atoms. Group or an alkoxy group having 1 to 10 carbon atoms. Also, R 11, R 12, R 13, R 14, and R 15 is preferably a hydrogen atom or an alkyl group having a carbon number of 1 ⁇ 5, R 11, R 12, R 13, R 14, and R 15 is more preferably any one of a hydrogen atom, a methyl group, and an ethyl group.
- the alkyl group having 1 to 10 carbon atoms represented by R 11 , R 12 , R 13 , R 14 and R 15 is defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 described above.
- the selected group can be selected.
- the alkoxy group having 1 to 10 carbon atoms represented by R 11 , R 12 , R 13 , R 14 , and R 15 is a linear or branched alkoxy group having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms.
- alkoxy groups include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, n-pentyloxy Group, n-hexyloxy group, n-heptyloxy group, n-octyloxy group, n-nonyloxy group, n-decyloxy group and the like.
- the alkoxy group is preferably a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, an s-butoxy group, a t-butoxy group, or an n-pentyloxy group.
- R 16 , R 17 , R 18 , and R 19 are each independently A hydrogen atom, a hydroxyl group, an alkyl group having 1 to 10 carbon atoms, or an alkoxy group having 1 to 10 carbon atoms is shown.
- R 16 , R 17 , R 18 , and R 19 are more preferably hydrogen atoms.
- n 1 represents 1 or 2
- n 2 represents an integer of 1 to 3.
- n 1 is preferably 1, and n 2 is preferably 2 .
- the alkyl group having 1 to 10 carbon atoms represented by R 16 , R 17 , R 18 , and R 19 is a group defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 described above. You can choose from.
- the alkoxy group having 1 to 10 carbon atoms represented by R 16 , R 17 , R 18 and R 19 is a group defined as the alkoxy group having 1 to 10 carbon atoms represented by R 11 to R 15 described above. You can choose from.
- R 16 and R 17 may form a carbonyl group with R 16 and R 17 and the carbon atom to which they are bonded.
- R 18 and R 19 may form a carbonyl group with R 18 and R 19 and the carbon atom to which they are bonded.
- Preferred — (— C (R 16 ) (R 17 ) —) n 1 — group includes, for example, —CH 2 — group, —CH 2 —CH 2 — group, group, —CH (CH 3 ) — group, Examples include —CO— group, but are not limited to these groups.
- Preferred — (— C (R 18 ) (R 19 ) —) n 2 — groups include, for example, —CH 2 — group, —CH 2 —CH 2 — group, —CH (CH 3 ) — group, —CO -Groups and the like, but are not limited to these groups.
- Z in the general formula (1) is an oxygen atom or methylene (—CH 2 —).
- J and k in the general formula (1) are each independently 0 or 1, and j + k never becomes 1. That is, if k is 1, j is 1, and if k is 0, j is 0.
- Y represents a hydrogen atom.
- X in the general formula (1) represents a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, a benzenesulfonyloxy group, a hydrogen atom, or a halogen atom.
- X include a hydrogen atom and a halogen atom, specifically a fluorine atom, a chlorine atom and a bromine atom, and for example, a chlorine atom is particularly preferred.
- the hydrogen atom in Y in the general formula (1) and X in the general formula (1) may be not only a normal hydrogen atom but also an isotope of a hydrogen atom.
- a preferred isotope is a deuterium atom.
- a in the general formula (1) of the present invention is a linear or branched alkylene group having 1 to 20 carbon atoms which may have a substituent, and 3 to 20 carbon atoms which may have a substituent.
- the linear or branched alkylene group having 1 to 20 carbon atoms which may have a substituent represented by A is a hydrogen atom from a linear or branched alkyl group having 1 to 20 carbon atoms.
- an alkylene group having 1 to 10 carbon atoms is preferable.
- methylene group, ethylene group, trimethylene group, tetramethylene group, n-propylene group, n-butylene group, n-hexylene group, n-heptylene group, n-octylene group, n-decylene group, etc. Can be mentioned.
- the alkylene group can have one or more substituents.
- Examples of the cycloalkylene group having 3 to 20 carbon atoms which may have a substituent represented by A include monocyclic, condensed cyclic, and bridged cycloalkylene groups, and specifically, cyclopropane And a divalent group obtained by removing two hydrogen atoms from a ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, and a cycloheptane ring.
- a cycloalkylene group having 3 to 10 carbon atoms is preferred.
- the cycloalkylene group can have one or more substituents.
- Examples of the arylene group having 6 to 20 carbon atoms which may have a substituent represented by A include monocyclic or condensed cyclic arylene groups, and specifically include benzene, naphthalene, indene, anthracene, Examples thereof include a divalent group obtained by removing two hydrogen atoms from azulene, pyrene, tetralin and the like. An arylene group having 6 to 15 carbon atoms is preferred.
- the substituent that the arylene group may have include a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, an alkyl group having 1 to 10 carbon atoms, an alkoxy group as described above, a carboxyl group, a hydroxyl group, An amino group, a cyano group, a nitro group, etc. are mentioned.
- the arylene group can have one or more substituents.
- the heterocyclic group which may have a substituent represented by A is preferably a heterocyclic group having 2 to 14 carbon atoms and containing at least one heteroatom, and having at least 1 heteroatom having 2 to 10 carbon atoms.
- a heterocyclic group containing 1 or more hetero atoms is more preferred, and a heterocyclic group containing 2 to 6 carbon atoms and containing at least one hetero atom is particularly preferred.
- Examples of the heterocyclic group having 2 to 14 carbon atoms and containing at least one heteroatom include, for example, an aliphatic heterocyclic group having 2 to 14 carbon atoms and containing at least one heteroatom, and 2 to 14 carbon atoms.
- An aromatic heterocyclic group containing at least one heteroatom can be mentioned.
- heterocyclic group may have include a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, an alkyl group having 1 to 10 carbon atoms, an alkoxy group as described above, a carboxyl group, and a hydroxyl group. Amino group, cyano group, nitro group and the like.
- the heterocyclic group can have one or more substituents.
- Ra and Rb each independently represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 10 carbon atoms.
- the alkyl group having 1 to 10 carbon atoms represented by Ra and Rb can be selected from the groups defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 described above.
- Examples of the aryl group having 6 to 10 carbon atoms represented by Ra and Rb include an aromatic monocyclic group, an aromatic polycyclic group and an aromatic condensed cyclic group, and an aromatic monocyclic group is preferred.
- the aryl group may have one or more substituents selected from an alkyl group having 1 to 10 carbon atoms or an alkoxy group having 1 to 6 carbon atoms as a substituent.
- substituents selected from an alkyl group having 1 to 10 carbon atoms or an alkoxy group having 1 to 6 carbon atoms as a substituent.
- Specific examples of the aryl group include a phenyl group, a tolyl group, and a xylyl group.
- Rc represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an aryl group having 6 to 10 carbon atoms.
- the alkyl group having 1 to 10 carbon atoms represented by Rc can be selected from the groups defined as the alkyl groups having 1 to 10 carbon atoms represented by R 2 and R 3 described above.
- the aryl group having 6 to 10 carbon atoms represented by Rc can be selected from the groups defined as the aryl group having 6 to 10 carbon atoms represented by Ra and Rb described above.
- bond part of Formula (A1) and Formula (A2) whichever may become the B side.
- skeleton of A examples include, for example, -alkylene-, -arylene-, -cycloalkylene-, -alkylene-cycloalkylene-, -arylene-cycloalkylene-, -arylene-alkylene-, -alkylene-arylene- Alkylene-, -alkylene-O-, -alkylene-O-alkylene-, -alkylene-O-arylene-, -alkylene-S-, -alkylene-S-alkylene-, -alkylene-S-arylene-, formula ( A1) -alkylene-, -formula (A1) -arylene-, -formula (A2) -alkylene-, -formula (A2) -arylene-, -alkylene-heterocycle-, -arylene-heterocycle-, -O- Heterocycle-, -S-heterocycle-, -formula
- Preferred skeletons of A include -arylene-alkylene-, -arylene-, and -arylene-alkylene-formula (A2) -alkylene-arylene-.
- A2 -alkylene-arylene-.
- -phenylene-alkylene-, -phenylene-, and -phenylene-alkylene-formula (A2) -alkylene-phenylene- are more preferable, -phenylene-alkylene having 1 to 3 carbon atoms, -phenylene- Or -phenylene-C1-C3 alkylene-Rc substituted with a formula (A2) -oxo group in which Rc is hydrogen is more preferable.
- B in the general formula (1) of the present invention represents a formula (B1), a formula (B2), a formula (B3), an oxygen atom, or a sulfur atom described below.
- the formula (B1) indicated by B will be described.
- Rd and Re each independently represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an alkoxy group having 1 to 10 carbon atoms.
- the alkyl group having 1 to 10 carbon atoms represented by Rd and Re can be selected from the groups defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 described above.
- Examples of the aryl group having 6 to 10 carbon atoms represented by Rd and Re include an aromatic monocyclic group, an aromatic polycyclic group, and an aromatic condensed cyclic group, and an aromatic monocyclic group is preferable.
- the aryl group may have one or more substituents selected from an alkyl group having 1 to 10 carbon atoms and an alkoxy group having 1 to 6 carbon atoms (the number of carbon atoms as a substituent is 1
- the alkyl group having ⁇ 10 can be selected from the groups defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 , and the alkoxy group having 1 to 6 carbon atoms as the substituent is R 11 to A group defined as an alkoxy group having 1 to 10 carbon atoms represented by R 15 ).
- aryl group represented by Rd and Re examples include a phenyl group, a tolyl group, and a xylyl group.
- the alkoxy group having 1 to 10 carbon atoms represented by Rd and Re can be selected from the groups defined as the alkoxy group having 1 to 10 carbon atoms represented by R 11 to R 15 described above.
- Rf represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms.
- the alkyl group having 1 to 10 carbon atoms represented by Rf can be selected from the groups defined as the alkyl group having 1 to 10 carbon atoms represented by R 2 and R 3 described above.
- any of the coupling portions of the formulas (B1), (B2), and (B3) may be on the D side.
- p and q in the general formula (1) each independently represent 0 or 1. For example, when p is 1 and q is 1, or when p is 1 and q is 0 Is more preferable.
- Examples of the solid phase carrier represented by D in the general formula (1) include all carriers that are solid at room temperature and hardly soluble in various organic solvents and water, and examples thereof include silica gel and polystyrene.
- Examples of the silica gel include basic silica gel such as acidic silica gel, neutral silica gel, NH 2 silica gel, amorphous silica, and mesoporous silica represented by MCM-41, SBA-15, FSM-16, and the like.
- Examples of the polystyrene include various polystyrenes obtained by polymerizing styrene with a copolymer of any equivalent amount of divinylbenzene or the like.
- solid phase carriers examples include JandaJels TM and TantaGel (registered trademark), which are polystyrene-like carriers having higher swellability. Further examples include trityl resin, PEG resin, Halolin TM Resin, oxime resin and peptide, and inorganic carriers such as iron oxide.
- alkylsulfonyl such as trifluoromethanesulfonyloxy ion (TfO ⁇ ), p-toluenesulfonyloxy ion (TsO ⁇ ), methanesulfonyloxy ion (MsO ⁇ ), and benzenesulfonyloxy ion (BsO ⁇ ).
- Examples thereof include ions such as 4 ⁇ , BPh 4 ⁇ , B (C 6 F 5 ) 4 ⁇ , and B (3,5- (CF 3 ) 2 C 6 F 3 ) 4 ⁇ .
- the diamine compound having cyclohexadiene represented by the general formula (5) which is an intermediate for producing the complex of the general formula (3), can be synthesized by the methods of Scheme 1 and Scheme 2.
- the general formula (5) is expressed according to the content described in “Supporting Information” of J. Am. Chem. Soc. 133 (2011) p. It can synthesize
- Scheme 1 L in Scheme 1 represents a leaving group.
- the general formula (5) can also be synthesized by sulfonylating the compound represented by the general formula (9) with a sulfonyl chloride represented by the general formula (8).
- the compound represented by General formula (9) is compoundable by making General formula (7) of the above-mentioned scheme 1 and diamine react.
- the ruthenium halide represented by RuV 3 is not particularly limited, and for example, ruthenium chloride, ruthenium bromide, ruthenium iodide and hydrates thereof can be used. Ruthenium chloride or hydrates thereof Is preferably used.
- the solvent used is not particularly limited, but 2-propanol, n-butanol, 2-butanol, n-pentanol, 2-pentanol, 3-pentanol, 3-methyl-1-butanol, cyclopentanol, 3 -Methoxy-1-propanol, 2-methoxyethanol, 2-ethoxyethanol, 2-isopropoxyethanol, n-hexanol, 3-methoxy-1-butanol, 3-methoxy-3-methyl-1-butanol, 2-hexanol Aliphatic alcohols such as 3-hexanol, cyclohexanol, n-heptanol, 2-heptanol, 3-heptanol, cycloheptanol, n-octanol, 2-octanol, 3-octanol, 4-octanol, cyclooctanol; Benzyl alcohol, 1- Aromatic alcohols such as
- a solvent may be used individually by 1 type and may be used in mixture of 2 or more types. By combining two or more solvents, the boiling point of the solvent can be adjusted to a desired range, and the reaction temperature can be adjusted when the reaction is performed under reflux. For example, a small amount of water may be mixed with alcohol.
- the amount of the compound of the general formula (5) to be used is 1 to 20 times molar equivalent, preferably 1 to 10 times molar equivalent, more preferably 1 to 5 times molar equivalent to the ruthenium atom.
- the amount of solvent used is not particularly limited as long as it dissolves ruthenium halide or a hydrate thereof at the reaction temperature.
- the volume is 2 to 100 times the volume of ruthenium halide or its hydrate (that is, 2 to 100 mL of solvent relative to 1 g of ruthenium halide or its hydrate.
- the same applies hereinafter preferably 2 to 75 times the volume.
- the reaction temperature varies depending on the solvent used, but is 60 ° C. or higher, preferably 100 ° C. or higher, and 200 ° C. or lower, preferably 160 ° C. or lower from the viewpoint of reaction efficiency.
- the reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr.
- This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- the solvent to be used is not particularly limited, but halogenated solvents such as methylene chloride, dichloroethane, chloroform, trifluoroethanol; aromatic hydrocarbons such as toluene and xylene; ethers such as diisopropyl ether and tetrahydrofuran; methanol, ethanol, Examples include alcohols such as 2-propanol, n-butanol, 2-butanol, and n-pentanol. Among these, chloroform, dichloromethane, and isopropanol are particularly preferable.
- a solvent may be used individually by 1 type and may be used in mixture of 2 or more types.
- the boiling point of the solvent can be adjusted to a desired range, and the reaction temperature can be adjusted when the reaction is performed under reflux.
- a small amount of water may be mixed with alcohol.
- the base used include inorganic substances such as sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate, lithium hydroxide, lithium hydrogen carbonate, lithium carbonate, cesium carbonate, magnesium hydroxide, magnesium carbonate, calcium hydroxide, and calcium carbonate.
- Bases examples include amines such as triethylamine, tripropylamine, tributylamine, pyridine, triisopropylamine. Of these, triethylamine is particularly preferred.
- the amount of the base used is 0.2 to 20 times molar equivalent, preferably 1.0 to 10 times molar equivalent to the ruthenium atom.
- the amount of the solvent used is not particularly limited, but is, for example, 2 to 50 times the volume of the substrate (solvent mL / substrate g).
- the reaction temperature is not particularly limited, but is 0 ° C. to the boiling point of each solvent, preferably room temperature to 80 ° C. While the reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr. This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- the solvent to be used is not particularly limited, and examples thereof include halogenated solvents such as methylene chloride, dichloroethane, chloroform and trifluoroethanol; aromatic hydrocarbons such as toluene and xylene; ethers such as diisopropyl ether and tetrahydrofuran. Of these, dichloromethane, toluene, and tetrahydrofuran are particularly preferable.
- a solvent may be used individually by 1 type and may be used in mixture of 2 or more types. By combining two or more solvents, the boiling point of the solvent can be adjusted to a desired range, and the reaction temperature can be adjusted when the reaction is performed under reflux.
- Examples of the base used include sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium hydroxide, potassium hydrogen carbonate, potassium carbonate, lithium hydroxide, lithium hydrogen carbonate, lithium carbonate, cesium carbonate, magnesium hydroxide, magnesium carbonate, water
- Examples of the base used include sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium hydroxide, potassium hydrogen carbonate, potassium carbonate, lithium hydroxide, lithium hydrogen carbonate, lithium carbonate, cesium carbonate, magnesium hydroxide, magnesium carbonate, water
- examples include inorganic bases such as calcium oxide and calcium carbonate. Of these, sodium hydroxide and potassium hydroxide are particularly preferred.
- the amount of the base used is 1 to 20 times molar equivalent, preferably 1.0 to 10 times molar equivalent, relative to the ruthenium atom.
- the amount of the solvent used is not particularly limited, and is, for example, 2 to 20 times the volume of the substrate (solvent mL / substrate g).
- the reaction temperature is not particularly limited, but is
- reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr.
- This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- X is a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, or a benzenesulfonyloxy group.
- Acids (XH) used are trifluoromethanesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, and the like.
- the amount of the acid used is 1 to 20 times molar equivalent, preferably 1.0 to 10 times molar equivalent to ruthenium.
- halogenated solvents such as a methylene chloride, dichloroethane, chloroform, trifluoroethanol
- Aromatic hydrocarbons such as toluene and xylene
- Ethers such as diisopropyl ether and tetrahydrofuran
- Methanol examples include alcohols such as ethanol.
- the amount of the solvent used is not particularly limited, but is, for example, 2 to 20 times the volume of the substrate (solvent mL / substrate g).
- the reaction temperature is not particularly limited, but is 0 ° C. to the boiling point of each solvent, preferably room temperature to 80 ° C. While the reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr.
- This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- the formic acid or hydrogen gas used is equimolar or more with respect to the ruthenium atom.
- the solvent used is not particularly limited, but alcohols such as methanol, ethanol and isopropanol, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane, acetonitrile, N, N-dimethyl Examples include aprotic polar solvents such as formamide and ethers such as diethyl ether and tetrahydrofuran. Among these, methanol and dichloromethane are preferred. One type of solvent may be used, or a plurality of solvents may be used in combination.
- the amount of the solvent used is not particularly limited, and is, for example, 2 to 20 times the volume of the substrate (solvent mL / substrate g).
- the reaction temperature is not particularly limited, but is 0 ° C. to the boiling point of each solvent, preferably room temperature to 80 ° C. While the reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr.
- This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- Examples of the metal G represented by GQ include silver (Ag), sodium (Na), potassium (K), lithium (Li), and the like.
- Examples of Q include alkanesulfonyloxy or arenesulfonyloxy such as trifluoromethanesulfonyloxy (TfO), p-toluenesulfonyloxy (TsO), methanesulfonyloxy (MsO), benzenesulfonyloxy (BsO), and BF 4 , SbF 6 , CF 3 COO, CH 3 COO, PF 6 , NO 3 , ClO 4 , SCN, OCN, ReO 4 , MoO 4 , BPh 4 , B (C 6 F 5 ) 4 , B ( 3 , 5- ( CF 3 ) 2 C 6 F 3 ) 4 and the like.
- Examples of metal salts represented by the G-Q is, AgOTf, AgOTs, AgOMs, AgOBs , AgBF 4, AgSbF 6, CF 3 COOAg, CH 3 COOAg, AgPF 6, AgNO 3, AgClO 4, AgSCN, AgOCN, AgReO 4, AgMoO 4, NaOTf, NaBF 4, NaSbF 6, CF 3 COONa, CH 3 COONa, NaPF 6, NaNO 3, NaClO 4, NaSCN, KOTf, KBF 4, KSbF 6, CF 3 COOK, CH 3 COOK, KPF 6 , KNO 3 , KClO 4 , KSCN, KBPh 4 , KB (C 6 F 5 ) 4 , KB (3,5- (CF 3 ) 2 C 6 F 3 ) 4 , LiOTf, LiBF 4 , LiSbF 6 , CF 3 COOLi, CH 3 COOLi, LiPF 6 , LiNO 3, LiClO 4, LiSCN, iBPh 4, Li
- the amount of the metal salt GQ used is equimolar or more with respect to the ruthenium atom.
- the solvent used is not particularly limited, but alcohols such as methanol, ethanol and isopropanol, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane, acetonitrile, N, N-dimethyl Examples include aprotic polar solvents such as formamide and ethers such as diethyl ether and tetrahydrofuran. Among these, methanol and dichloromethane are preferred. One type of solvent may be used, or a plurality of solvents may be used in combination.
- the amount of the solvent used is not particularly limited, and is, for example, 2 to 20 times the volume of the substrate (solvent mL / substrate g).
- the reaction temperature is not particularly limited, but is 0 ° C. to the boiling point of each solvent, preferably room temperature to 80 ° C. While the reaction time varies depending on the reaction substrate to be used, it is 30 min to 20 hr, preferably 1 hr to 12 hr. This production method is preferably carried out in an inert gas such as nitrogen gas or argon gas.
- a reduction product can be produced by reducing the organic compound in the presence of a hydrogen donor using the above-described solid-supported ruthenium complex as a catalyst.
- the reduction reaction of the present invention includes a method for producing an alcohol by reducing the carbonyl group of a carbonyl compound in the presence of a hydrogen donor in the presence of the above-described solid-supported ruthenium complex, and an imino compound of an imine compound.
- a method for producing an amine by reducing a group is a method for producing an alcohol by reducing the carbonyl group of a carbonyl compound in the presence of a hydrogen donor in the presence of the above-described solid-supported ruthenium complex, and an imino compound of an imine compound.
- an optically active alcohol can be produced by asymmetric reduction of the carbonyl group of the carbonyl compound, and an optically active alcohol can be obtained by reducing the imino group of the imine compound.
- Active amines can be produced.
- the hydrogen donor include those generally used in hydrogen transfer reduction reactions such as formic acid or an alkali metal salt thereof, isopropanol which is an alcohol having a hydrogen atom at the ⁇ -position of a carbon atom substituted with a hydroxyl group. If there is no particular limitation.
- hydrogen gas can also be used as a hydrogen donor.
- the reduction reaction is preferably carried out in the presence of a base.
- a base examples include trimethylamine, triethylamine, triisopropylamine, 1,4-diazabicyclo [2,2,2] octane (DABCO), 1,8-diazabicyclo [5,4,0] undec-7-ene (DBU), etc.
- a preferred base is triethylamine.
- the base is used in an excess amount with respect to the solid-supported ruthenium complex, for example, 1 to 100,000 times in molar ratio.
- triethylamine When triethylamine is used, it is preferably used in an amount of 1 to 10,000 times with respect to the solid-supported ruthenium complex.
- the hydrogen donor when the hydrogen donor is formic acid, it is preferable to use an amine as the base.
- the formic acid and the amine may be added separately to the reaction system, You may mix and add to a reaction system.
- formic acid and amine can be mixed and used in an arbitrary ratio.
- an azeotropic mixture of formic acid and amine may be prepared in advance.
- a preferable azeotrope of formic acid and amine includes, for example, triethylamine formate (5: 2 (molar ratio)) azeotrope.
- the reaction solvent is usually a liquid hydrogen donor, but can be used as a non-hydrogen donor solvent such as toluene, tetrahydrofuran, acetonitrile, dimethylformamide, dimethyl sulfoxide, acetone, methylene chloride, methanol, ethanol, n-butanol. Can be used alone or in combination.
- a formate the reaction can be carried out in a two-layer system using water as a co-solvent in combination with an organic solvent in order to dissolve the formate. In this case, a phase transfer catalyst may be used together to accelerate the reaction.
- an alcohol solvent such as methanol, ethanol, isopropanol, trifluoroethanol, hexafluoro-2-propanol or the like is preferable.
- the amount of the solid-supported ruthenium complex represented by the general formulas (1) to (3) as the catalyst is such that the molar ratio (S / C) of the substrate (carbonyl compound or imine) (S) to the ruthenium metal atom (C). It is selected from the range of 10 to 1000000, preferably 50 to 15000.
- the amount of the hydrogen donor relative to the carbonyl compound or imine is usually used in an equimolar amount or more, and when the hydrogen donor is formic acid or a salt thereof, the molar amount is preferably 1.5 times or more, It is used in a range of 40-fold molar amount or less, preferably 20-fold molar amount or less, and is preferably 2 to 15-fold molar amount from the viewpoint of molecular efficiency.
- the hydrogen donor is isopropanol or the like, it is used in a large excess with respect to the substrate from the viewpoint of reaction equilibrium, and is usually used in a range of 1000 mol times or less.
- the reaction temperature is selected from the range of ⁇ 20 to 100 ° C., preferably 0 to 70 ° C.
- the reaction pressure is not particularly limited, and is usually 0.5 to 2 atm, preferably under normal pressure. Moreover, when using hydrogen gas, it is 5 MPa or less normally. While the reaction time varies depending on the catalyst ratio, it is 1 to 100 hours, usually 2 to 50 hours.
- the ruthenium complex supported on the solid phase which is a catalyst
- the solid phase which is a catalyst
- the solid-supported ruthenium complex separated by filtration or the like can be reused for the next reaction as it is.
- the produced product or optically active substance can be separated and purified by general operations such as distillation, extraction, chromatography, and recrystallization.
- a continuous flow reaction can be performed by filling a column with a ruthenium complex supported on a solid phase as a catalyst and feeding a substrate.
- a quantitative pump such as an HPLC pump
- no catalyst separation operation is required, and reduction products are produced by reducing organic compounds.
- the reaction conditions are the same as above.
- a substrate, a solvent, a base, and a hydrogen donor can be mixed, and the mixture can be reacted by feeding it to a column.
- the reaction can be performed by mixing a substrate, a solvent, and a base, sending the mixed solution to the column, and passing hydrogen gas through the column.
- the NMR spectra used for complex identification and purity determination in the following Examples and the like were measured with a Mercury Plus 300 4N type apparatus manufactured by Varian Technology Japan Limited or a Bruker BioSpin Avance III 500 System.
- Chirazil-DEX CB (0.25 mm ⁇ 25 m, 0.25 ⁇ m) (Varian) or HP-1 (0.32 mm ⁇ 30 m, 0.25 ⁇ m) (Agilent Technology) was used.
- MS measurement JMS-T100GCV manufactured by JEOL Ltd. or LCMS-IT-TOF manufactured by Shimadzu Corporation was used.
- the symbol in an Example represents the following meaning.
- Ph phenyl DPEN: 1,2-diphenylethylenediamine DIPEA: diisopropylethylamine Ts: tosyl Et 3 N: triethylamine Me: methyl 2-MeOEtOH: 2-methoxyethanol PS: polystyrene HFIP: 1,1,1,3,3,3 -Hexafluoro-2-propanol THF: Tetrahydrofuran
- Example 1 (1R, 2R) -N 1- (2-((4-Methylcyclohexa-1,4-dienyl) methoxy) ethyl) -1,2-diphenylethane-1,2-diamine (compound 2) Synthesis A 300 mL four-necked reaction flask was equipped with a three-way cock, a stirrer bar, and a thermometer, and the interior was purged with nitrogen. Under a nitrogen stream, 5.0 g (23.5 mmol) of (R, R) -DPEN, 30.38 g (18.8 mmol) of a 20 wt% toluene solution of Compound 1, and 4.99 g of Na 2 CO 3 were placed in this reaction flask.
- Example 3 Synthesis of ruthenium dimer complex (compound 5) To a 100 mL eggplant flask, 0.26 g (0.4 mmol) of Compound 4 obtained in Example 2, 70 mg (0.267 mmol) of RuCl 3 .3H 2 O, and 7 mL of 2-MeOEtOH were added, and after nitrogen substitution, 110 When the mixture was stirred for 1 hour in an oil bath at 0 ° C., it was confirmed that the reaction solution became red and that ruthenium was complexed.
- Example 4 Synthesis of Silica Gel-Supported Ruthenium Dimer Complex (Compound 6A) (Solid-Supported Ruthenium Complex of Formula (3))
- silica gel manufactured by Kanto Chemical Co., Inc., neutral / spherical 63-210 ⁇ m
- the solvent was recovered with an evaporator.
- 3 g of the obtained sandy solid was placed in a 200 mL eggplant flask equipped with a Dean-Stark refluxer, 50 mL of toluene was added, and the mixture was heated for 2 hours while extracting water and methanol distilled off in an oil bath at 140 ° C.
- Example 6 Synthesis of silica gel-supported ruthenium dimer complex (compound 6B) (solid-phase-supported ruthenium complex of formula (3)) To a 2-MeOEtOH solution of compound 5 obtained in Example 3, 7.6 g of silica gel (manufactured by Kanto Chemical Co., Ltd., neutral / spherical 40-50 ⁇ m) was added and stirred, and then the solvent was recovered with an evaporator. 3 g of the obtained sandy solid was placed in a 200 mL eggplant flask equipped with a Dean-Stark refluxer, 50 mL of toluene was added, and the mixture was heated for 2 hours while extracting water and methanol distilled off in an oil bath at 140 ° C.
- Example 7 Reduction reaction of acetophenone using silica gel-supported ruthenium dimer complex (Compound 6B) The reaction and catalyst recovery were performed in the same manner as in Example 5 except that the compound 6B obtained in Example 6 was used and the reaction time was changed as shown in Table 2 below.
- Example 8 Synthesis of Compound 8A
- polystyrene beads having a sulfonyl chloride functional group (compound 7) (1.9 mmol / g, manufactured by Aldrich), 1.0 g (1.9 mmol), (R, R) -DPEN 0.807 g (3.8 mmol) ), 0.77 g (7.6 mmol) of triethylamine and 10 mL of chloroform were added, and the atmosphere was purged with nitrogen, followed by stirring in an oil bath at 50 ° C. for 2.5 hours. Thereafter, the reaction solution was cooled to room temperature, filtered through a Kiriyama funnel, the solid was washed with chloroform, and dried under reduced pressure to obtain 1.33 g (yield 100% (weight conversion)) of Compound 8A.
- Example 9 Synthesis of Compound 9A
- a 100 mL Schlenk tube 0.5 g (0.95 mmol) of the compound 8A obtained in Example 8, 1.91 g (1.187 mmol) of a 20 wt% toluene solution of the compound 1, 0.245 g (1.9 mmol) of DIPEA, And 10 ml of xylene was added, and it stirred for 9 hours in a 140 degreeC oil bath. Thereafter, the reaction solution was cooled to room temperature, filtered through a Kiriyama funnel, the solid was washed with 10 mL of toluene and 10 mL of chloroform, and dried under reduced pressure to obtain 0.66 g (yield 99% (weight conversion)) of Compound 9A. It was.
- Example 10 Synthesis of polystyrene-supported ruthenium dimer complex (compound 10A) (solid-phase-supported ruthenium complex of formula (3)) To a 50 mL eggplant flask, 0.2 g (0.38 mmol) of Compound 9A obtained in Example 9, 99.35 mg (0.38 mmol) of RuCl 3 .3H 2 O, 5 mL of 2-MeOEtOH, and 1 mL of water were added. After purging with nitrogen, the reaction was carried out in an oil bath at 110 ° C. for 2 hours.
- reaction solution was cooled to room temperature, filtered through a Kiriyama funnel, and the resulting solid was washed with 20 mL of methanol and then dried under reduced pressure to obtain 0.211 g of Compound 10A, which is a solid phase-supported ruthenium complex of the present invention.
- Example 11 Reduction Reaction of Acetophenone Using Polystyrene-Supported Ruthenium Dimer Complex (Compound 10A)
- Compound 10A Into a 15 mL Schlenk tube, 13.15 mg of compound 10A obtained in Example 10 (0.005 mmol in terms of monomer complex), 0.3 g of acetophenone (2.5 mmol), and triethylamine formate (5: 2 (molar ratio))
- the reaction was started at 60 ° C. after adding 1.25 mL of boiling product and purging with nitrogen.
- the amount of formic acid relative to acetophenone was 9 times the molar amount.
- the conversion rate and optical purity were measured 2 hours after the reaction, the conversion rate was 20.4% and the optical purity was 94.3% ee.
- the reaction was continued as it was, and the conversion rate and optical purity were measured at a reaction time of 9 hours.
- the conversion rate was 93.8% and the optical purity was 95.7% ee.
- Example 12 Synthesis of Compound 9B
- a 50 mL eggplant flask 0.5 g (0.95 mmol) of polystyrene beads having a sulfonyl chloride functional group (Compound 7) (Aldrich, 1.9 mmol / g), 0.516 g of Compound 2 obtained in Example 1 (1 .425 mmol), 0.29 g (2.85 mmol) of triethylamine, and 20 mL of chloroform were added, and the atmosphere was replaced with nitrogen, followed by stirring in an oil bath at 50 ° C. for 2 hours. Thereafter, the reaction solution was cooled to room temperature, filtered through a Kiriyama funnel, the solid was washed with chloroform, and dried under reduced pressure to obtain 0.935 g of Compound 9B.
- Example 13 Synthesis of polystyrene-supported ruthenium dimer complex (compound 10B) (solid-phase-supported ruthenium complex of formula (3)) After adding 0.2 g (0.38 mmol) of the compound 9B obtained in Example 12, 99.35 mg (0.38 mmol) of RuCl 3 .3H 2 O, and 5 mL of 2-MeOEtOH to the 50 mL eggplant flask, and replacing the inside with nitrogen The mixture was reacted in an oil bath at 110 ° C. for 2 hours.
- reaction solution was cooled to room temperature, filtered through a Kiriyama funnel, and the resulting solid was washed with 20 mL of methanol and then dried under reduced pressure to obtain 0.240 g of Compound 10B which is a solid-supported ruthenium complex of the present invention.
- Example 14 Reduction Reaction of Acetophenone Using Polystyrene-Supported Ruthenium Dimer Complex (Compound 10B)
- Compound 10B obtained in Example 13
- 0.3 g (2.5 mmol) of acetophenone, and triethylamine formate 5: 2 (molar ratio)
- the reaction was started at 60 ° C. after adding 1.25 mL of boiling product and purging with nitrogen.
- the amount of formic acid relative to acetophenone was 9 times the molar amount.
- the conversion rate and optical purity after 3 hours and 5 hours of reaction are as shown in Table 3 below.
- Example 16 N-((1R, 2R) -2- (5- (4-methylcyclohexa-1,4-dienyl) pentylamino) -1,2-diphenylethyl) -4- (2- ( Synthesis of trimethoxysilyl) ethyl) benzenesulfonamide (Compound 13)
- a three-way cock, a stirrer bar, and a thermometer were attached to a 100 mL four-necked reaction flask, and the interior was purged with nitrogen.
- Example 18 Synthesis of silica gel-supported ruthenium dimer complex (compound 15A) (solid-phase-supported ruthenium complex of formula (3)) To a 2-MeOEtOH solution of compound 14 obtained in Example 17, 10.28 g of silica gel (manufactured by Kanto Chemical Co., Ltd., neutral / spherical 40-50 ⁇ m) was added and stirred, and then the solvent was recovered with an evaporator. 3 g of the obtained sandy solid was placed in a 200 mL eggplant flask equipped with a Dean-Stark refluxer, 50 mL of toluene was added, and the mixture was heated for 2 hours while extracting water and methanol distilled off in an oil bath at 140 ° C.
- Example 19 Reduction Reaction of Acetophenone Using Silica Gel-Supported Ruthenium Dimer Complex (Compound 15A)
- the reaction and catalyst recovery were performed in the same manner as in Example 5 except that the compound 15A obtained in Example 18 was used and the reaction time was changed as shown in Table 4 below.
- Example 20 Synthesis of Silica Gel-Supported Ruthenium Monomer Complex (Compound 6B ′) (Solid-Supported Ruthenium Complex of Formula (1)) To a 100 mL eggplant flask, 1.0 g of compound 6B obtained in Example 6 (0.012 mmol in terms of monomer complex) was taken, 0.26 g (0.1 mmol) of triethylamine and 10 mL of chloroform were added, and the inside was purged with nitrogen Then, the mixture was stirred in an oil bath at 40 ° C. for 2 hours.
- Compound 6B ′ Solid-Supported Ruthenium Complex of Formula (1)
- Example 21 Reduction Reaction of Acetophenone Using Silica Gel-Supported Ruthenium Monomer Complex (Compound 6B ′)
- the compound 6B ′ obtained in Example 20 ′ 0.41 g (0.01 mmol), acetophenone 0.6 g (5.0 mmol), and triethylamine formate (5: 2 (molar ratio)) azeotrope 2.5 mL was added, and the reaction was carried out at 60 ° C. for 5 hours.
- the amount of formic acid relative to acetophenone was 9 times the molar amount.
- the conversion and optical purity were measured by GC, 97.8% conv. 96.8% ee.
- Example 22 Synthesis of polystyrene-supported ruthenium monomer complex (compound 10B ') (solid-phase-supported ruthenium complex of formula (1)) To a 100 mL eggplant flask, 0.132 g (0.05 mmol in terms of monomer complex) of the compound 10B obtained in Example 13 was added, 0.26 g (0.1 mmol) of triethylamine and 5 mL of chloroform were added, and the inside was purged with nitrogen Then, the mixture was stirred in an oil bath at 40 ° C. for 2 hours.
- Example 23 Reduction Reaction of Acetophenone Using Polystyrene-Supported Ruthenium Monomer Complex (Compound 10B ′)
- the reaction was carried out at 60 ° C. for 5 hours.
- the amount of formic acid relative to acetophenone was 9 times the molar amount.
- the conversion and optical purity were measured by GC, 96.5% conv. 97.8% ee.
- Example 24 Reduction reaction of propiophenone using silica gel-supported ruthenium dimer complex (compound 6B)
- compound 6B silica gel-supported ruthenium dimer complex
- 0.205 g of compound 6B obtained in Example 6 0.205 g of compound 6B obtained in Example 6 (0.005 mmol in terms of monomer complex), 0.335 g (2.5 mmol) of propiophenone, and triethylamine formate (5: 2 (molar ratio))
- the reaction was started at 60 ° C.
- the amount of formic acid relative to the substrate was a 9-fold molar amount.
- the conversion and optical purity were measured by GC, and 97.6% conv. 96.9% ee.
- Example 25 Reduction reaction of acetylfuran using a silica gel-supported ruthenium dimer complex (Compound 6B)
- a silica gel-supported ruthenium dimer complex Compound 6B
- 0.205 g of compound 6B obtained in Example 6 0.275 g of acetylfuran (2.5 mmol)
- triethylamine formate 5: 2 (molar ratio)
- the reaction was started at 60 ° C.
- the amount of formic acid relative to the substrate was a 9-fold molar amount.
- the conversion and optical purity were measured by GC, and 100% conv. 98.4% ee.
- Example 26 Reduction reaction of o-methoxyacetophenone using silica gel-supported ruthenium dimer complex (Compound 6B)
- a 15 mL Schlenk tube 0.205 g of compound 6B obtained in Example 6 (0.005 mmol in terms of monomer complex), 0.375 g (2.5 mmol) of o-methoxyacetophenone, and triethylamine formate (5: 2 (molar ratio) ))
- the reaction was started at 60 ° C.
- the amount of formic acid relative to the substrate was a 9-fold molar amount.
- the reaction time was 10 hours, the conversion and optical purity were measured by GC, and 96.0% conv. 94.1% ee.
- Example 27 Hydrogenation-reduction reaction of ⁇ -hydroxyacetophenone using silica gel-supported ruthenium dimer complex (Compound 6B)
- a 100 mL autoclave 0.205 g of compound 6B obtained in Example 6 (0.005 mmol in terms of monomer complex) and 0.07 g (0.5 mmol) of ⁇ -hydroxyacetophenone were added, and the atmosphere was replaced with nitrogen. 4 mL was added. The reaction was started at 60 ° C. under pressure of 3.0 MPa with hydrogen gas. After 8 hours of reaction, the conversion and optical purity were measured by GC, and it was determined that 97.3% conv. 82% ee.
- Example 28 Reduction reaction of cyclic imine using silica gel-supported ruthenium dimer complex (compound 6B)
- 0.205 g of compound 6B obtained in Example 6 0.102 g (0.5 mmol) of cyclic imine represented by the above formula
- triethylamine formate 5: 2 ( Molar ratio) 1.25 mL of azeotrope and 3 mL of dichloromethane were added, and the reaction was started at 30 ° C. after purging with nitrogen.
- the amount of formic acid relative to the cyclic imine was 9 times the molar amount. After the reaction time of 20 hours, the conversion and optical purity were measured by GC, and 98.0% conv. 90% ee.
- Example 29 Synthesis of silica gel-supported ruthenium cationic monomer complex (compound 6B′-BF 4 ) (solid-phase-supported ruthenium complex of formula (2)) To a 100 mL eggplant flask, 1.0 g (0.012 mmol) of the compound 6B ′ obtained in Example 20 was added, 9.3 mg (0.048 mmol) of AgBF 4 , 3 mL of methanol, and 5 mL of dichloromethane were added, and the inside was purged with nitrogen Then, the mixture was stirred in an oil bath at 40 ° C. for 2 hours.
- reaction solution was cooled to room temperature, and the solid was collected by filtration with a Kiriyama funnel and washed with 30 mL of chloroform and subsequently with 30 mL of methanol.
- the obtained solid was dried under reduced pressure to obtain a ruthenium cationic monomer complex (compound 6B′-BF 4 ) supported on the silica gel of the present invention.
- Example 30 Hydrogeno-reduction reaction of 2-methylquinoline using silica gel-supported ruthenium cationic monomer complex (compound 6B'-BF 4 ) To a 100 mL autoclave were added 0.205 g (0.005 mmol) of the compound 6B′-BF 4 obtained in Example 29 and 0.07 g (0.5 mmol) of 2-methylquinoline, and after nitrogen substitution, 1.4 mL of HFIP was added. added. The reaction was started at 40 ° C. under pressure of 3.0 MPa with hydrogen gas. After the reaction time was 20 hours, the conversion and optical purity were measured by GC, and 95.0% conv. 91% ee.
- Example 31 4- (N-((1R, 2R) -2-((2-((4-methylcyclohexa-1,4-dien-1-yl) methoxy) ethyl) amino) -1, Synthesis of 2-diphenylethyl) sulfamoyl) benzoic acid (compound 16) To a 30 mL eggplant flask, 61 mg (0.28 mmol) of 4-chlorosulfonylbenzoic acid was added and the atmosphere was replaced with nitrogen, followed by dropwise addition of 56 mg (0.56 mmol) of triethylamine dissolved in 2 mL of THF.
- Example 32 Synthesis of polystyrene-supported ligand (Compound 17)
- a 30 mL eggplant flask 202 mg (0.37 mmol) of Compound 16 obtained in Example 31, 1-ethyl-3- [3- (dimethylamino) propyl] carbodiimide hydrochloride (abbreviated as EDCI) 85 mg (0.444 mmol), Dimethylaminopyridine (abbreviated as DMAP) 54 mg (0.444 mmol) and 1 mL of methylene chloride were added to perform nitrogen substitution. After that, 1 mL of methylene chloride was added and stirred at room temperature for 20 hours.
- EDCI 1-ethyl-3- [3- (dimethylamino) propyl] carbodiimide hydrochloride
- DMAP Dimethylaminopyridine
- 1 mL of methylene chloride was added to perform nitrogen substitution. After that, 1 mL of methylene chloride was added and stirred at
- the reaction mixture was filtered on a Kiriyama funnel, and the filtrate was placed in a 30 mL eggplant flask. 10 mL of water and 10 mL of chloroform were added to the eggplant flask and washed by stirring for 10 minutes. Thereafter, the mixture was filtered again, further washed with methanol, and dried to obtain 241 mg of Compound 17.
- Example 33 Synthesis of polystyrene-supported ruthenium dimer complex (compound 18) (solid-phase-supported ruthenium complex of formula (3)) To a 30 mL eggplant flask, 0.2 g (0.31 mmol) of the compound 17 obtained in Example 32 and 80 mg (0.31 mmol) of RuCl 3 .3H 2 O were added, and nitrogen substitution was performed. After that, 5 mL of 2-methoxyethanol was added and stirred at 110 ° C. for 2 hours.
- Example 34 Reduction Reaction of Acetophenone Using Polystyrene-Supported Ruthenium Dimer Complex (Compound 18)
- Compound 18 obtained in Example 33 (0.1 mmol in terms of monomer complex), 0.62 g (5 mmol) of acetophenone, and triethylamine formate (5: 2 (molar ratio)) azeotrope
- the reaction was started at 60 ° C.
- the amount of formic acid relative to acetophenone was 9 times the molar amount. Table 5 shows the conversion and optical purity after 5 hours and 7 hours of reaction.
- Example 35 Reduction reaction of continuous flow acetophenone packed with silica gel-supported ruthenium dimer complex (compound 6B) 2.5 g of compound 6B obtained in Example 6 (0.06 mmol in terms of monomer complex) was methanol After being suspended in the column and put into a column via a packer, methanol was fed with an HPLC pump and the packing was terminated when the pressure became constant. Next, this column was put in a column oven at 60 ° C., and a mixed solution of 6 ml (51.4 mmol) of acetophenone, 25 ml of triethylamine formate (5: 2 (molar ratio)), and 125 ml of methanol was mixed with an HPLC pump.
- the solution was continuously fed at a flow rate of 0.05 ml / min.
- the amount of formic acid relative to acetophenone was about 3.6 times the molar amount.
- the reaction solution was continuously fed for 10 hours and passed through the column and analyzed by GC every hour. As a result, the conversion rate was 100% and the selectivity was 97% ee.
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Abstract
Description
その中で、M.Willsらは、ジアミン部分とルテニウム錯体に配位する芳香族化合物(arene)部位とを炭素鎖で繋いだ錯体を報告しており、これらの錯体は従来の触媒より高い活性を示すことが知られている(J. Am. Chem. Soc. 127 (2005) p. 7318;J. Org. Chem. 71 (2006) p. 7035;Org. Biomol. Chem. 5 (2007) p. 1093;Org. Lett. 9 (2007) p. 4659;J. Organometallic Chem. 693 (2008) p. 3527;Dalton Trans. 39 (2010) p. 1395など)。
また、本発明者らは、ジアミン部分とルテニウム錯体に配位する芳香族化合物(arene)部位とを酸素原子を含む側鎖で繋いだ錯体を報告しており、これらの錯体はさらに高い活性を示すことが知られている(特開2012-67071号公報およびJ. Am. Chem. Soc. 133 (2011) p. 14960等参照)。
一方、前述のJ. Am. Chem. Soc. 117 (1995) p. 7562;J. Am. Chem. Soc. 118 (1996) p. 2521;J. Am. Chem. Soc. 118 (1996) p. 4916で報告されているような、ジアミン部分とルテニウム錯体に配位する芳香族化合物(arene)部位とを炭素鎖もしくは酸素原子を含む側鎖で繋いでいない従来から用いられている錯体を、シリカゲルなどの固相に担持した触媒がいくつか開発されてきた。(Org. Lett. 6 (2004) p. 169;Chem. Commun. (2004) p. 2070;Eur. J. Org. Chem. (2005) p. 3221等参照)。
本発明は、このような課題を解決しようとするものである。
即ち、本発明は、以下の内容を含むものである。
一般式(1)で表される固相担持ルテニウム錯体。
R2及びR3は、それぞれ独立して、炭素数1~10のアルキル基;炭素数1~10のアルキル基、炭素数1~10のアルコキシ基、および、ハロゲン原子から選択される置換基を有していてもよいフェニル基;又は炭素数1~10のアルキル基から選択される置換基を有していてもよい炭素数3~8のシクロアルキル基を示す。R2及びR3は、一緒になって環を形成してもよい。
R11、R12、R13、R14、及びR15は、それぞれ独立して、水素原子、炭素数1~10のアルキル基、又は炭素数1~10のアルコキシ基を示す。
R16、R17、R18、及びR19は、それぞれ独立して、水素原子、ヒドロキシル基、炭素数1~10のアルキル基、又は炭素数1~10のアルコキシ基を示す。R16及びR17は、R16とR17とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
R18及びR19は、R18とR19とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
Zは、酸素原子又はメチレン(-CH2-)を示す。
n1は1又は2を、n2は1~3の整数を示す。
Yは水素原子を示す。
Xは、トリフルオロメタンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基、ベンゼンスルホニルオキシ基、水素原子、又はハロゲン原子を示す。
j及びkは、それぞれ独立して、0又は1を示すが、j+kが1になることはない。
Aは、置換基を有してもよい直鎖状又は分岐鎖状の炭素数1~20のアルキレン基、置換基を有してもよい炭素数3~20のシクロアルキレン基、置換基を有してもよい炭素数6~20のアリーレン基、置換基を有してもよい複素環基、酸素原子、硫黄原子、
から選択される二価の基、または、これらの二価の基が複数結合して形成された基を表す。なお、式(A1)及び式(A2)の結合部分は、どちらがB側になってもよい。
Bは、
Dは固相担体を示す。
p、qは、それぞれ独立して、0又は1を表す。)
R2、R3、R11、R12、R13、R14、R15、R16、R17、R18、R19、Z、n1、n2、Y、A、B、D、p、及びqは、上記で定義した通りであり、Q-はカウンターアニオンを示す。)
R2、R3、R11、R12、R13、R14、R15、R16、R17、R18、R19、Z、n1、n2、Y、A、B、D、p、及びqは、上記で定義した通りであり、Vはハロゲン原子を示す。)
一般式(1)~(3)のいずれかで表される固相担持ルテニウム錯体及び水素供与体の存在下、カルボニル化合物のカルボニル基を還元することを特徴とする光学活性アルコールの製造方法。
一般式(1)~(3)のいずれかで表される固相担持ルテニウム錯体及び水素供与体の存在下、イミン化合物のイミノ基を還元することを特徴とする光学活性アミンの製造方法。
水素供与体が、ギ酸、ギ酸アルカリ金属塩及び水酸基置換炭素のα位炭素原子に水素原子を有するアルコールの中から選ばれる上記のいずれかの製造方法。
水素供与体が、水素である上記のいずれかの製造方法。
一般式(1)~(3)のいずれかで表される固相担持ルテニウム錯体を含む還元用触媒。
還元用触媒が、不斉還元用触媒である上記触媒。
また、一般式(1)及び(2)で表される固相担持ルテニウム錯体は、ジアミン配位子の2個の窒素原子が共有結合又は配位結合でルテニウム原子に結合し、当該ジアミンと結合した芳香族化合物部位もルテニウム原子に配位結合する、3座配位子を有し、かつ、芳香族化合物部位とジアミン部分とを連結する鎖状部分を有し、ジアミン部分に結合したスルホニル基から伸びる側鎖の末端が固相担体に結合している錯体である。
一般式(1)、(2)、及び(3)における*印は、当該*印が付されている炭素原子が不斉炭素原子となる場合があることを示している。当該炭素原子が不斉炭素原子となる場合には、それらの光学活性体としてもよいし、光学活性体の混合物であってもよいし、ラセミ体(ラセミ化合物を含む)であってもよい。本発明の好ましい態様としては、これらの炭素原子が不斉炭素原子となる場合には、これらの光学活性体が挙げられる。
一般式(2)で表される固相担持ルテニウム錯体は、一般式(1)で表される固相担持ルテニウム錯体におけるRu-Xの結合が、Ru+-Q-のイオン結合となる場合の錯体である。
一般式(3)で表される固相担持ルテニウム錯体は、ハロゲン原子であるVを介した二量体(ダイマー)であり、芳香族化合物部位がルテニウム原子に配位している錯体である。一般式(3)で表される固相担持ルテニウム錯体は、一般式(1)又は(2)で表される固相担持ルテニウム錯体を製造する際の中間体として有用なだけでなく、それ自体も還元触媒としての活性を有している錯体である。
<一般式(1)の固相担持ルテニウム錯体>
本発明の一般式(1)のR2及びR3は、それぞれ独立して、炭素数1~10のアルキル基;炭素数1~10のアルキル基、炭素数1~10のアルコキシ基、およびハロゲン原子から選択される置換基を有していてもよいフェニル基;又は炭素数1~10のアルキル基から選択される置換基を有していてもよい炭素数3~8のシクロアルキル基を示す。R2及びR3は、一緒になって環を形成してもよい。また、R2及びR3の双方が炭素数1~10のアルキル基、炭素数1~10のアルコキシ基、およびハロゲン原子から選択される置換基を有していてもよいフェニル基であることが好ましく、R2及びR3の双方が置換基を有さないフェニル基であることがより好ましい。
本発明の一般式(1)のR2及びR3で示される炭素数1~10のアルキル基としては、炭素数1~10、好ましくは炭素数1~5の直鎖又は分岐のアルキル基が挙げられる。具体的なアルキル基としては、例えばメチル基、エチル基、n-プロピル基、イソプロピル基、n-ブチル基、イソブチル基、s-ブチル基、t-ブチル基、n-ペンチル基、n-ヘキシル基、n-ヘプチル基、n-オクチル基、n-ノニル基及びn-デシル基等が挙げられる。当該アルキル基としては、メチル基、エチル基、n-プロピル基、イソプロピル基、n-ブチル基、イソブチル基、s-ブチル基、t-ブチル基、n-ペンチル基であることが好ましい。
次に、本発明の一般式(1)のR2及びR3で示される、フェニル基が有しうる置換基としての炭素数1~10のアルキル基、炭素数1~10のアルコキシ基、及び、ハロゲン原子について説明する。なお、当該フェニル基は、1つまたは複数の置換基を有しうる。
置換基としての炭素数1~10のアルキル基は、例えば前記した式(1)のR2及びR3で示される炭素数1~10のアルキル基として定義された基から選択することができる。
置換基としての炭素数1~10のアルコキシ基としては、炭素数1~10、好ましくは炭素数1~5の直鎖又は分岐のアルコキシ基が挙げられ、具体的なアルコキシ基としては、例えばメトキシ基、エトキシ基、n-プロポキシ基、イソプロポキシ基、n-ブトキシ基、イソブトキシ基、s-ブトキシ基、t-ブトキシ基、n-ペンチルオキシ基、n-ヘキシルオキシ基、n-ヘプチルオキシ基、n-オクチルオキシ基、n-ノニルオキシ基及びn-デシルオキシ基等が挙げられる。当該アルコキシ基としては、メトキシ基、エトキシ基、n-プロポキシ基、イソプロポキシ基、n-ブトキシ基、イソブトキシ基、s-ブトキシ基、t-ブトキシ基、n-ペンチルオキシ基であることが好ましい。
置換基としてのハロゲン原子としては、例えば、フッ素原子、塩素原子及び臭素原子が挙げられる。
式(1)のR2及びR3で示される当該シクロアルキル基が有しうる置換基としての炭素数1~10のアルキル基は、例えば前記した式(1)のR2及びR3で示される炭素数1~10のアルキル基として定義された基から選択することができメチル基、イソプロピル基、t-ブチル基等が好ましい。当該シクロアルキル基は、1つまたは複数の置換基を有しうる。
また、R2及びR3が一緒になって環を形成する場合、隣接する炭素原子と共に4~8員、好ましくは5~8員のシクロアルカン環を形成する。好ましいシクロアルカン環としては、シクロペンタン環、シクロヘキサン環及びシクロヘプタン環が挙げられ、これらの環は、炭素数1~10のアルキル基から選択される置換基を有していても良い。置換基として具体的な当該アルキル基としては、メチル基、イソプロピル基、t-ブチル基等が挙げられる。当該環は、1つまたは複数の置換基を有しうる。
R11、R12、R13、R14、及びR15で示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
R11、R12、R13、R14、及びR15で示される炭素数1~10のアルコキシ基としては、炭素数1~10、好ましくは炭素数1~5の直鎖又は分岐のアルコキシ基が挙げられ、具体的なアルコキシ基としては、例えばメトキシ基、エトキシ基、n-プロポキシ基、イソプロポキシ基、n-ブトキシ基、イソブトキシ基、s-ブトキシ基、t-ブトキシ基、n-ペンチルオキシ基、n-ヘキシルオキシ基、n-ヘプチルオキシ基、n-オクチルオキシ基、n-ノニルオキシ基及びn-デシルオキシ基等が挙げられる。当該アルコキシ基としては、メトキシ基、エトキシ基、n-プロポキシ基、イソプロポキシ基、n-ブトキシ基、イソブトキシ基、s-ブトキシ基、t-ブトキシ基、n-ペンチルオキシ基であることが好ましい。
また、一般式(1)中のn1は、1又は2を示し、n2は1~3の整数を示す。n1は1であることが好ましく、n2は2であることが好ましい。
R16、R17、R18、及びR19で示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
R16、R17、R18、及びR19で示される炭素数1~10のアルコキシ基としては、上述したR11~R15で表される炭素数1~10のアルコキシ基として定義された基から選択することができる。
R16とR17は、R16とR17とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
R18とR19は、R18とR19とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
好ましい-(-C(R16)(R17)-)n1-基としては、例えば、-CH2-基、-CH2-CH2-基、基、-CH(CH3)-基、-CO-基などが挙げられるが、これらの基に限定されるものではない。
好ましい-(-C(R18)(R19)-)n2-基としては、例えば、-CH2-基、-CH2-CH2-基、-CH(CH3)-基、-CO-基などが挙げられるが、これらの基に限定されるものではない。
一般式(1)のj及びkは、それぞれ独立して、0又は1であり、j+kが1になることはない。即ち、kが1であればjも1であり、kが0であればjも0である。
Yは水素原子を示す。
一般式(1)のXは、トリフルオロメタンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基、ベンゼンスルホニルオキシ基、水素原子、又はハロゲン原子を表す。好ましいXとしては、水素原子及びハロゲン原子、具体的にはフッ素原子、塩素原子及び臭素原子等が挙げられ、例えば塩素原子が特に好ましい。
一般式(1)のY、並びに一般式(1)のXにおける水素原子としては、通常の水素原子だけでなく水素原子の同位体であってもよい。好ましい同位体としては重水素原子が挙げられる。
当該アルキレン基が有しうる置換基としては、フッ素原子、塩素原子、臭素原子、及び、ヨウ素原子などのハロゲン原子、上述したようなアルコキシ基、カルボキシル基、オキソ基(=O)、ヒドロキシル基、アミノ基、シアノ基、ニトロ基などが挙げられる。当該アルキレン基は、1つまたは複数の置換基を有しうる。
当該シクロアルキレン基が有しうる置換基としては、フッ素原子、塩素原子、臭素原子、ヨウ素原子などのハロゲン原子、炭素数1~10のアルキル基、上述したようなアルコキシ基、カルボキシル基、オキソ基(=O)、ヒドロキシル基、アミノ基、シアノ基、ニトロ基などが挙げられる。当該シクロアルキレン基は、1つまたは複数の置換基を有しうる。
当該アリーレン基が有しうる置換基としては、フッ素原子、塩素原子、臭素原子、ヨウ素原子などのハロゲン原子、炭素数1~10のアルキル基、上述したようなアルコキシ基、カルボキシル基、ヒドロキシル基、アミノ基、シアノ基、ニトロ基などが挙げられる。当該アリーレン基は、1つまたは複数の置換基を有しうる。
当該複素環基が有しうる置換基としては、フッ素原子、塩素原子、臭素原子、ヨウ素原子などのハロゲン原子、炭素数1~10のアルキル基、上述したようなアルコキシ基、カルボキシル基、ヒドロキシル基、アミノ基、シアノ基、ニトロ基などが挙げられる。当該複素環基は、1つまたは複数の置換基を有しうる。
Ra及びRbで示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
Ra及びRbで示される炭素数6~10のアリール基としては、芳香族単環式基、芳香族多環式基又は芳香族縮合環式基が挙げられ、芳香族単環式基が好ましい。また、当該アリール基は、置換基として炭素数1~10のアルキル基又は炭素数1~6のアルコキシ基から選択される置換基を1つまたは複数有していてもよい。当該アリール基としては、具体的にはフェニル基、トリル基、キシリル基などが挙げられる。
Rcで示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
Rcで示される炭素数6~10のアリール基としては、上述したRa及びRbで表される炭素数6~10のアリール基として定義された基から選択することができる。
なお、式(A1)及び式(A2)の結合部分は、どちらがB側になってもよい。
好ましいAの骨格としては、-アリーレン-アルキレン-、-アリーレン-、および-アリーレン-アルキレン-式(A2)-アルキレン-アリーレン-が挙げられる。Aの骨格としては、-フェニレン‐アルキレン‐、‐フェニレン‐、および-フェニレン-アルキレン-式(A2)-アルキレン-フェニレン-がより好ましく、‐フェニレン‐炭素数1~3のアルキレン‐、‐フェニレン‐、または、-フェニレン-炭素数1~3のアルキレン-Rcが水素である式(A2)-オキソ基で置換された炭素数1~3のアルキレン-フェニレン-であることがより好ましい。
Bで示される式(B1)について説明する。
Rd及びReで示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
Rd及びReで示される炭素数6~10のアリール基としては、芳香族単環式基、芳香族多環式基又は芳香族縮合環式基が挙げられ、芳香族単環式基が好ましい。また、当該アリール基は、炭素数1~10のアルキル基および炭素数1~6のアルコキシ基から選択される1つ又は複数の置換基を有していてもよい(置換基としての炭素数1~10のアルキル基は、R2及びR3で表される炭素数1~10のアルキル基として定義された基から選択でき、置換基としての炭素数1~6のアルコキシ基は、R11~R15で表される炭素数1~10のアルコキシ基として定義された基から選択できる)。Rd及びReで示される当該アリール基としては、具体的にはフェニル基、トリル基、キシリル基などが挙げられる。Rd及びReで示される炭素数1~10のアルコキシ基としては、上述したR11~R15で表される炭素数1~10のアルコキシ基として定義された基から選択することができる。
Rfで示される炭素数1~10のアルキル基としては、上述したR2及びR3で表される炭素数1~10のアルキル基として定義された基から選択することができる。
また、一般式(1)中のpおよびqはそれぞれ独立して、0又は1を示すが、例えば、pが1でqが1である場合、又は、pが1でqが0である場合が、より好ましい。
また、他の固相担体としては、より膨潤性を高めたポリスチレン類似の担体であるJandaJelsTMや、TantaGel(登録商標)などが挙げられる。さらにトリチルレジン、PEGレジン、HalolinkTMResin、オキシム樹脂やペプチド、さらに酸化鉄などの無機担体なども挙げられる。
式(2)中、R2、R3、R11、R12、R13、R14、R15、R16、R17、R18、R19、Z、n1、n2、Y、A、B、D、p、及びqは、上記で定義した通りである。
式(2)中、Q-はカウンターアニオンを示す。具体的なカウンターアニオンとしては、トリフルオロメタンスルホニルオキシイオン(TfO-)、p-トルエンスルホニルオキシイオン(TsO-)、メタンスルホニルオキシイオン(MsO-)、ベンゼンスルホニルオキシイオン(BsO-)などのアルキルスルホニルオキシイオン又はアレーンスルホニルオキシイオン;又はBF4 -、SbF6 -、CF3COO-、CH3COO-、PF6 -、NO3 -、ClO4 -、SCN-、OCN-、ReO4 -、MoO4 -、BPh4 -、B(C6F5)4 -、及びB(3,5-(CF3)2C6F3)4 -などのイオンが挙げられる。
式(3)中、R2、R3、R11、R12、R13、R14、R15、R16、R17、R18、R19、Z、n1、n2、Y、A 、B、D、p、及びqは、上記で定義した通りである。
式(3)中、Vはハロゲン原子を示す。
一般式(3)のVで示すハロゲン原子は、塩素原子、臭素原子、ヨウ素原子のいずれかを表す。一般式(3)におけるすべてのVが同じハロゲン原子であってもよいし、異なるハロゲン原子の組み合わせでもよい。
以下のスキームの*、R2、R3、X、Y、Z、V、Q-、R11、R12、R13、R14、R15、R16、R17、R18、R19、A、B、D、n1、n2、p、q、j、及びkは、上記で定義した通りである。
一般式(3)の錯体を製造するための中間体である一般式(5)で表されるシクロヘキサジエンを有するジアミン化合物は、スキーム1やスキーム2の方法により合成することができる。
スキーム1に示したように、一般式(5)は、J. Am. Chem. Soc. 133 (2011) p. 14960のSupporting Information(14962頁右欄参照)に記載された内容に従い、一般式(6)で表される一方にスルホニル基を導入したジアミン化合物に一般式(7)で表されるシクロヘキサジエン誘導体を反応させることにより合成できる。
また、スキーム2のように、一般式(5)は、一般式(9)で表される化合物を、一般式(8)で表されるスルホニルクロリドなどによりスルホニル化して合成することもできる。
なお、一般式(9)で表される化合物は、上記したスキーム1の一般式(7)とジアミンを反応させることにより合成できる。
用いる溶媒は、特に限定はされないが、2-プロパノール、n-ブタノール、2-ブタノール、n-ペンタノール、2-ペンタノール、3-ペンタノール、3-メチル-1-ブタノール、シクロペンタノール、3-メトキシ-1-プロパノール、2-メトキシエタノール、2-エトキシエタノール、2-イソプロポキシエタノール、n-ヘキサノール、3-メトキシ-1-ブタノール、3-メトキシ-3-メチル-1-ブタノール、2-ヘキサノール、3-ヘキサノール、シクロヘキサノール、n-ヘプタノール、2-ヘプタノール、3-ヘプタノール、シクロヘプタノール、n-オクタノール、2-オクタノール、3-オクタノール、4-オクタノール、シクロオクタノール等の脂肪族アルコール;フェノール、ベンジルアルコール、1-フェニルエタノール、2-フェニルエタノール、o-クレゾール、m-クレゾール、p-クレゾール、2-メチルベンジルアルコール、3-メチルベンジルアルコール、4-メチルベンジルアルコールなどの芳香族アルコール;エチレングリコール、1,2-プロパンジオール、1,3-プロパンジオール、1,2-ブタンジオール、1,3-ブタンジオール、1,4-ブタンジオール、エチレングリコール-n-ブチルエーテル、エチレングリコール-iso-ブチルエーテル、エチレングリコール-n-ヘキシルエーテルなどのジオール及びその誘導体が挙げられる。溶媒は1種単独で用いてもよく、2種以上を混合して用いてもよい。2種以上の溶媒を組み合わせることにより、溶媒の沸点を所望の範囲に調整することができ、還流下で反応を行う場合に反応温度を調整することができる。例えば、アルコールに少量の水を混合して用いてもよい。
一般式(5)の化合物の使用量は、ルテニウム原子に対して1~20倍モル当量、好ましくは1~10倍モル当量、より好ましくは1~5倍モル当量である。
溶媒の使用量は、反応温度においてハロゲンルテニウム又はその水和物を溶解する量であればよく、特に制限されない。例えば、ハロゲンルテニウム又はその水和物の2~100倍容量(すなわち、ハロゲンルテニウム又はその水和物1gに対して溶媒2~100mL。以下同様。)、好ましくは2~75倍容量である。
反応温度は、用いる溶媒によっても異なるが、反応効率の観点から60℃以上、好ましくは100℃以上であり、200℃以下、好ましくは160℃以下である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
[一般式(1)のうち、j=1であり、Xがハロゲン原子の錯体の製造方法]
一般式(1)のうち、j=1であり、Xがハロゲン原子である錯体は、スキーム4で示すように、適切な溶媒の存在下、一般式(3)の錯体に塩基を作用させることにより合成することができる。
用いられる塩基としては、炭酸水素ナトリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸カリウム、水酸化リチウム、炭酸水素リチウム、炭酸リチウム、炭酸セシウム、水酸化マグネシウム、炭酸マグネシウム、水酸化カルシウム、炭酸カルシウムなどの無機塩基;トリエチルアミン、トリプロピルアミン、トリブチルアミン、ピリジン、トリイソプロピルアミンなどのアミン類が挙げられる。これらの中でも特にトリエチルアミンが好適である。塩基の使用量としては、ルテニウム原子に対して0.2~20倍モル当量、好ましくは1.0~10倍モル当量である。
溶媒の使用量は、特に制限されないが、例えば、基質に対して2倍容量~50倍容量(溶媒mL/基質g)である。
反応温度は、特に限定はされないが、0℃~各溶媒の沸点以下の温度であり、好ましくは室温~80℃である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
一般式(1)のうち、j=0である錯体は、スキーム5で示すように、適切な溶媒の存在下、一般式(3)の錯体に塩基を作用させることにより合成することができる。
用いられる塩基としては、水酸化ナトリウム、炭酸水素ナトリウム、炭酸ナトリウム、水酸化カリウム、炭酸水素カリウム、炭酸カリウム、水酸化リチウム、炭酸水素リチウム、炭酸リチウム、炭酸セシウム、水酸化マグネシウム、炭酸マグネシウム、水酸化カルシウム、炭酸カルシウムなどの無機塩基類が挙げられる。これらの中でも特に水酸化ナトリウム、水酸化カリウムが好適である。塩基の使用量としては、ルテニウム原子に対して1~20倍モル当量、好ましくは1.0~10倍モル当量である。
溶媒の使用量は、特に制限されないが、例えば、基質に対して2倍容量~20倍容量(溶媒mL/基質g)である。
反応温度は、特に限定はされないが、0℃~各溶媒の沸点以下の温度であり、好ましくは室温~80℃である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
一般式(1)のうち、j=1であり、Xがトリフルオロメタンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基、又はベンゼンスルホニルオキシ基である錯体は、スキーム5で得られる一般式(1)のうちj=0の錯体に対して、対応する適切な酸類で処理することにより合成することができる。
製造方法をスキーム6に示す。
用いられる酸類(X-H)としては、トリフルオロメタンスルホン酸、p-トルエンスルホン酸、メタンスルホン酸、ベンゼンスルホン酸などである。用いる酸の使用量としては、ルテニウムに対して1~20倍モル当量、好ましくは1.0~10倍モル当量である。
用いる溶媒としては特に限定はされないが、例えば、塩化メチレン、ジクロロエタン、クロロホルム、トリフルオロエタノール等のハロゲン化溶媒;トルエン、キシレン等の芳香族炭化水素類;ジイソプロピルエーテル、テトラヒドロフラン等のエーテル類;メタノール、エタノールなどのアルコール類が挙げられる。
溶媒の使用量は、特に制限されないが、例えば基質に対して2倍容量~20倍容量(溶媒mL/基質g)である。
反応温度は、特に限定はされないが、0℃~各溶媒の沸点以下の温度であり、好ましくは室温~80℃である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
一般式(1)のうち、j=1でありXが水素原子である錯体は、スキーム7で示すように、一般式(3)で表される錯体に、ギ酸や水素ガスなど反応させることにより合成することができる。
製造方法をスキーム7に示す。
用いられる溶媒としては特に限定されないが、メタノール、エタノール、イソプロパノール等のアルコール、トルエン、キシレン等の芳香族炭化水素、ジクロロメタン、1,2-ジクロロエタンなどのハロゲン化炭化水素、アセトニトリル、N,N-ジメチルホルムアミド等の非プロトン性極性溶媒、ジエチルエーテル、テトラヒドロフラン等のエーテル等が挙げられ、これらの中でもメタノールやジクロロメタンが好ましい。溶媒は、1種類を使用してもよいし、複数を混合して使用してもよい。
溶媒の使用量は、特に制限されないが、例えば、基質に対して2倍容量~20倍容量(溶媒mL/基質g)である。
反応温度は、特に限定はされないが、0℃~各溶媒の沸点以下の温度であり、好ましくは室温~80℃である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
また、一般式(1)のうち、j=1でありXが水素原子である錯体は、(a)スキーム5で得られた一般式(1)のうち、j=0である錯体に、ギ酸や水素ガスなどを反応させる、(b)スキーム6で得られた一般式(1)のうち、j=1でありXがトリフルオロメタンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基、又はベンゼンスルホニルオキシ基である錯体に、ギ酸や水素ガスなどを反応させる、又は(c)後述するスキーム8で合成される一般式(2)の錯体に、ギ酸や水素ガスなどを反応させる、ことにより合成することもできる。
これらの反応条件は、スキーム7の条件と同様である。
一般式(2)で表される固相担持ルテニウム錯体は、一般式(1)のうちj=1でありXがハロゲン原子である錯体とG-Qで表される金属塩を反応させることにより製造することができる。
製造方法をスキーム8に示す。
当該G-Qで表される金属塩の例としては、AgOTf、AgOTs、AgOMs、AgOBs、AgBF4、AgSbF6、CF3COOAg、CH3COOAg、AgPF6、AgNO3、AgClO4、AgSCN、AgOCN、AgReO4、AgMoO4、NaOTf、NaBF4、NaSbF6、CF3COONa、CH3COONa、NaPF6、NaNO3、NaClO4、NaSCN、KOTf、KBF4、KSbF6、CF3COOK、CH3COOK、KPF6、KNO3、KClO4、KSCN、KBPh4、KB(C6F5)4、KB(3,5-(CF3)2C6F3)4、LiOTf、LiBF4、LiSbF6、CF3COOLi、CH3COOLi、LiPF6、LiNO3、LiClO4、LiSCN、LiBPh4、LiB(C6F5)4、LiB(3,5-(CF3)2C6F3)4などが挙げられ、特に限定はされないが、例えばAgBF4が使用しやすい。
用いられる溶媒としては特に限定されないが、メタノール、エタノール、イソプロパノール等のアルコール、トルエン、キシレン等の芳香族炭化水素、ジクロロメタン、1,2-ジクロロエタンなどのハロゲン化炭化水素、アセトニトリル、N,N-ジメチルホルムアミド等の非プロトン性極性溶媒、ジエチルエーテル、テトラヒドロフラン等のエーテル等が挙げられ、これらの中でもメタノールやジクロロメタンが好ましい。溶媒は、1種類を使用してもよいし、複数を混合して使用してもよい。
溶媒の使用量は、特に制限されないが、例えば、基質に対して2倍容量~20倍容量(溶媒mL/基質g)である。
反応温度は、特に限定はされないが、0℃~各溶媒の沸点以下の温度であり、好ましくは室温~80℃である。
反応時間は用いる反応基質により異なるが、30分~20時間、好ましくは1時間~12時間である。本製造法は、窒素ガス、アルゴンガス等の不活性ガス中で行うことが好ましい。
錯体調製後は、反応液の濃縮又は貧溶媒の添加等の一般的な晶析手法により、目的とする固相担持ルテニウム錯体を分離することができる。
また、上記の錯体の調製において、ハロゲン化金属塩(G-X)が副生する場合には、必要に応じて水洗の操作を行ってもよい。
上述した固相担持ルテニウム錯体を触媒として用い、かつ、水素供与体の存在下で、有機化合物を還元して、還元生成物を製造することができる。
本発明の還元反応は、上述した固相担持ルテニウム錯体を触媒として用い、かつ、水素供与体の存在下で、カルボニル化合物のカルボニル基を還元してアルコールを製造する方法、及び、イミン化合物のイミノ基を還元してアミンを製造する方法、を含む。また、上述した固相担持ルテニウム錯体が光学活性体の場合は、カルボニル化合物のカルボニル基を不斉還元して光学活性アルコールを製造することができ、また、イミン化合物のイミノ基を還元して光学活性アミンを製造することができる。
水素供与体としては、ギ酸又はそのアルカリ金属塩、水酸基が置換している炭素原子のα位に水素原子を有するアルコールであるイソプロパノール等の水素移動型還元反応に一般的に用いられるようなものであれば特に限定されない。また、水素供与体としては水素ガスも用いることができる。
上記水素供与体と塩基との組み合わせの中で、水素供与体がギ酸の場合にはアミンを塩基として用いるのが好ましく、この場合、ギ酸とアミンは別々に反応系に添加しても良いし、混合して反応系に添加しても良い。混合して用いる場合は、ギ酸とアミンを任意の割合で混合して使用することができる。また、あらかじめギ酸とアミンの共沸混合物を調製して用いてもよい。好ましいギ酸とアミンの共沸混合物としては、例えば、ギ酸トリエチルアミン(5:2(モル比))共沸混合物などが挙げられる。
反応溶媒は通常、水素供与体が液体であればそれを利用できるが、トルエン、テトラヒドロフラン、アセトニトリル、ジメチルホルムアミド、ジメチルスルホキシド、アセトン、塩化メチレン等の非水素供与性溶媒やメタノール、エタノール、n-ブタノールを単独又は混合して使用することも可能である。ギ酸塩を用いる時などは、ギ酸塩を溶解させるため水を助溶媒として有機溶媒と併せて用い、二層系で反応を行うこともできる。この場合、反応を加速させるため相間移動触媒を併せて用いても良い。また、水素供与体として水素ガスを用いる場合は、メタノール、エタノール、イソプロパノール、トルフルオロエタノール、ヘキサフルオロ-2-プロパノール等のアルコール溶媒が好ましい。
カルボニル化合物又はイミン類に対する水素供与体の量としては、通常等モル量以上用いられ、このうち水素供与体がギ酸又はその塩である場合には、1.5倍モル量以上が好ましく、また、40倍モル量以下、好ましくは20倍モル量以下の範囲で用いられ、分子効率の観点から、2~15倍モル量であることが好ましい。一方、水素供与体がイソプロパノール等の場合には、反応平衡の観点から基質に対して大過剰量用いられ、通常1000モル倍以下の範囲で用いられる。
反応温度は-20~100℃、好ましくは0~70℃の範囲から選ばれる。
反応圧力は特に限定されず、通常0.5~2気圧、好ましくは常圧のもとで行われる。また、水素ガスを用いる場合は通常5MPa以下である。
反応時間は触媒比によって異なるが1~100時間、通常は2~50時間である。
反応操作としては、例えば、基質、溶媒、塩基、および水素供与体を混合し、混合液をカラムに送液することにより、反応させることができる。また、水素供与体が水素ガスの場合は、基質、溶媒、および塩基を混合し、混合液をカラムに送液するとともに、水素ガスをカラムに通すことにより反応させることができる。
以下、実施例により本発明を詳細に説明するが、本発明はこれらに限定されるものではない。
また、実施例中の記号は以下の意味を表す。
Ph:フェニル
DPEN:1,2-ジフェニルエチレンジアミン
DIPEA:ジイソプロピルエチルアミン
Ts:トシル
Et3N:トリエチルアミン
Me:メチル
2-MeOEtOH:2-メトキシエタノール
PS:ポリスチレン
HFIP:1,1,1,3,3,3-ヘキサフルオロ-2-プロパノール
THF:テトラヒドロフラン
300mL4つ口反応フラスコに三方コック、スターラーバー及び温度計を取り付け、内部を窒素置換した。この反応フラスコに、窒素気流下にて(R,R)-DPEN 5.0g(23.5mmol)、化合物1の20重量%トルエン溶液30.38g(18.8mmol)、Na2CO3 4.99g(47.1mmol)、DIPEA 6.09g (47.1mmol)、及びキシレン 100mLを加え、140℃のオイルバスにて11時間攪拌した。その後、水60mL及びトルエン50mLを投入し攪拌した後、静置し分液を行った。さらに有機層を水30mLにて洗浄し、有機層をエバポレーターにて濃縮した後、シリカゲルカラムクロマトグラフィー(酢酸エチル100%→酢酸エチル:メタノール=1:1(容量比))にて精製することにより、化合物2を4.39g(収率64.3%)得た。
1H-NMR (CDCl3, 300MHz): δ 7.30-7.10(m, 10H), 5.62 (m, 1H), 5.45 (m, 1H), 4.00 (d, 1H), 3.80 (m, 2H), 3.78 (d, 1H), 3.50-3.38 (m, 2H), 2.70-2.50 (m, 6H), 2.45-2.25 (brs, 3H), 1.70 (s, 3H);
1H-NMR (CDCl3, 300MHz): δ 7.40 (d, 2H), 7.20-6.85 (m, 8H), 5.63 (m, 1H), 5.43 (m, 1H), 4.41 (d, 1H), 3.90 (m, 1H), 3.80 (m, 1H), 3.59 (s, 9H), 3.60-3.40 (m, 2H), 3.75-3.60 (m, 2H), 3.60 (brs, 2H), 1.70 (s, 3H), 0.95-0.85 (m, 2H);
反応時間1時間、2時間、及び5時間後の転化率及び光学純度をGCにて測定した。結果は表1の通りである。
反応終了後の溶液に酢酸エチル5mLを加えた後、桐山ロートにて固体触媒をろ取し、本発明の固相担持ルテニウム錯体を回収した。
回収した固相担持ルテニウム錯体を用いて、1回目と同様の操作で2回目の反応を行った。反応時間1時間、2時間、及び5時間後の転化率及び光学純度は表1の通りである。反応終了後、1回目と同様の操作により、本発明の固相担持ルテニウム錯体を回収した。
2回目の反応に使用した後回収した固相担持ルテニウム錯体を用いて、1回目と同様の操作で3回目の反応を行った。反応時間1時間、2時間、及び7時間後の転化率及び光学純度は表1の通りである。
反応時間3時間及び5時間後の転化率及び光学純度は次表3の通りである。
反応終了後の溶液に酢酸エチル5mLを加えた後、反応液の上澄みの液をシリンジで抜き取り、シュレンク管内に残った固体触媒に1回目の反応と同様にして新たな基質とギ酸トリエチルアミン(5:2)共沸物を加えて2回目の反応を行った。反応時間1時間及び3時間後の転化率及び光学純度は次表3の通りである。
反応終了後、1回目と同様の操作により反応液を抜き取り、シュレンク管内に残った固体触媒に1回目の反応と同様にして新たな基質とギ酸トリエチルアミン共沸物を加えて3回目の反応を行った。反応時間1時間及び4時間後の転化率及び光学純度は次表3の通りである。
1H-NMR (CDCl3, 300MHz): δ 7.38-7.10 (m, 10H), 5.60-5.30 (m, 2H), 4.22-4.04 (m, 1H), 3.85-3.70 (m, 1H), 2.78-2.16 (m, 9H), 2.08 (s, 1H), 2.03-1.92 (m, 1H), 1.90 (t, 2H), 1.78 (s, 1H), 1.65 (s, 2H) 1.58-1.20 (m, 4H);
1H-NMR (CDCl3, 300MHz): δ 7.62 (d, 1H), 7.50-6.78 (m, 14H), 5.56-5.20 (m, 2H), (m, 1H), 3.60 (s, 9H), 3.10-2.18 (m, 9H), 2.10-1.56 (m, 9H), 1.45-1.20 (m, 4H), 1.05-0.80 (m, 2H);
[実施例17] ルテニウムダイマー錯体(化合物14)の合成
15mLシュレンク管に実施例20で得られ化合物6B ’0.41g (0.01mmol)、アセトフェノン 0.6g (5.0mmol)、及びギ酸トリエチルアミン(5:2(モル比))共沸物2.5mLを加え、窒素置換した後60℃にて5時間反応を行った。アセトフェノンに対するギ酸の量は、9倍モル量であった。GCにて転化率と光学純度を測定したところ、97.8% conv.、96.8% eeであった。
反応時間10時間後、GCにて転化率及び光学純度を測定したところ、97.6%conv.、96.9%eeであった。
反応時間5時間後、GCにて転化率及び光学純度を測定したところ、100%conv.、98.4%eeであった。
反応時間10時間後、GCにて転化率及び光学純度を測定したところ、96.0%conv.、94.1%eeであった。
反応時間8時間後、GCにて転化率及び光学純度を測定したところ、97.3%conv.、82%eeであった。
反応時間20時間後、GCにて転化率及び光学純度を測定したところ、98.0%conv.、90%eeであった。
反応時間20時間後、GCにて転化率及び光学純度を測定したところ、95.0%conv.、91%eeであった。
30mLナスフラスコに、4-クロロスルホニル安息香酸61mg(0.28mmolを加え、窒素置換した後に、THF2mLに溶解したトリエチルアミン56mg(0.56mmol)を滴下した。これを撹拌しながら氷水で0℃に冷却し、THF2mLに溶解した化合物2 100mg(0.28mmol,実施例1で合成)を滴下し、反応させた。30分後に反応を停止し、シリカゲルクロマトグラフィー(クロロホルム:メタノール=20:1(容量比))にて精製し、化合物16を420mg(0.768mmol,収率28%)得た。
1H-NMR (CDCl3, 300MHz): δ 8.25-7.90 (m, 14H), 6.40-6.20 (m, 1H), 5.82-4.98 (m, 2H), 4.88-4.70 (m, 1H), 4.00-3.18 (m, 5H), 2.96-2.40 (m, 4H), 2.22-1.86 (m, 2H), 1.78-1.40 (m, 4H), 0.08 (s, 1H);
30mLナスフラスコに、実施例31で得た化合物16 202mg(0.37mmol)、1-エチル-3-[3-(ジメチルアミノ)プロピル]カルボジイミド塩酸塩(EDCIと略す) 85mg(0.444mmol)、ジメチルアミノピリジン(DMAPと略す)54mg(0.444mmol)、及び塩化メチレン1mLを加え、窒素置換を行った。そののち塩化メチレンを1mL追加し、室温にて20時間撹拌した。反応停止後、桐山漏斗上で濾過し、濾過物を30mLナスフラスコに入れた。水10mLおよびクロロホルム10mLをナスフラスコへ加え、10分撹拌して洗浄した。その後、再び濾過し、メタノールにてさらに洗浄したあと乾燥し、化合物17を241mg得た。
30mLナスフラスコに、実施例32で得た化合物17 0.2g(0.31mmol)、及びRuCl3・3H2O 80mg(0.31mmol)を加え、窒素置換を行った。そののち2-メトキシエタノールを5mL追加し、110℃にて2時間撹拌した。反応停止後、桐山漏斗上で濾過し、濾過物をメタノールにて洗浄したのちに乾燥し、本発明のポリスチレンに担持されたルテニウムダイマー錯体(化合物18)を192mg得た。
反応時間5時間及び7時間後の転化率及び光学純度は表5の通りである。
反応終了後の溶液に酢酸エチル5mLを加えた後、桐山ロートにて固体触媒をろ取し、本発明の固相担持ルテニウム錯体を回収した。
回収した固相担持ルテニウム錯体を用いて、1回目と同様の操作で2回目の反応を行った。反応時間5時間及び7時間後の転化率及び光学純度は表5の通りである。
実施例6で得られた化合物6B 2.5g (モノマー錯体に換算すると0.06 mmol)をメタノールに懸濁させパッカー経由でカラムに投入した後、HPLCポンプにてメタノールを送液して圧力が一定になったところで充填を終了とした。次にこのカラムを60℃のカラムオーブンに入れ、アセトフェノン6ml(51.4mmol)、ギ酸トリエチルアミン(5:2(モル比))共沸物25ml、及びメタノール125mlの混合溶液をHPLCポンプを用いて0.05ml/minの流速で連続送液した。アセトフェノンに対するギ酸の量は、約3.6倍モル量であった。
反応開始2時間で転化率は100%、選択率97% eeであった。そのまま連続10時間送液しカラムを通過した反応液を1時間毎にGCにて分析した結果、何れも転化率100% 選択率97% eeであった。
Claims (10)
- 一般式(1)で表される固相担持ルテニウム錯体
R2及びR3は、それぞれ独立して、炭素数1~10のアルキル基;炭素数1~10のアルキル基、炭素数1~10のアルコキシ基、および、ハロゲン原子から選択される置換基を有していてもよいフェニル基;又は炭素数1~10のアルキル基から選択される置換基を有していてもよい炭素数3~8のシクロアルキル基を示す。R2及びR3は、一緒になって環を形成してもよい。
R11、R12、R13、R14、及びR15は、それぞれ独立して、水素原子、炭素数1~10のアルキル基、又は炭素数1~10のアルコキシ基を示す。
R16、R17、R18、及びR19は、それぞれ独立して、水素原子、ヒドロキシル基、炭素数1~10のアルキル基、又は炭素数1~10のアルコキシ基を示す。R16及びR17は、R16とR17とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
R18及びR19は、R18とR19とこれらが結合している炭素原子とでカルボニル基を形成してもよい。
Zは、酸素原子又はメチレン(-CH2-)を示す。
n1は1又は2を、n2は1~3の整数を示す。
Yは水素原子を示す。
Xは、トリフルオロメタンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基、ベンゼンスルホニルオキシ基、水素原子、又はハロゲン原子を示す。
j及びkは、それぞれ独立して、0又は1を示すが、j+kが1になることはない。
Aは、置換基を有してもよい直鎖状又は分岐鎖状の炭素数1~20のアルキレン基、置換基を有してもよい炭素数3~20のシクロアルキレン基、置換基を有してもよい炭素数6~20のアリーレン基、置換基を有してもよい複素環基、酸素原子、硫黄原子、
から選択される二価の基、または、これらの二価の基が複数結合して形成された基を表す。なお、式(A1)及び式(A2)の結合部分は、どちらがB側になってもよい。
Bは、
Dは固相担体を示す。
p、qは、それぞれ独立して、0又は1を表す。) - 請求項1~3のいずれかに記載の固相担持ルテニウム錯体及び水素供与体の存在下で、有機化合物を還元することを特徴とする還元生成物を製造する方法。
- 請求項1~3のいずれかに記載の固相担持ルテニウム錯体及び水素供与体の存在下、カルボニル化合物のカルボニル基を還元することを特徴とする光学活性アルコールの製造方法。
- 請求項1~3のいずれかに記載の固相担持ルテニウム錯体及び水素供与体の存在下、イミン化合物のイミノ基を還元することを特徴とする光学活性アミンの製造方法。
- 水素供与体が、ギ酸、ギ酸アルカリ金属塩及び水酸基置換炭素のα位炭素原子に水素原子を有するアルコールの中から選ばれる請求項4~6のいずれかに記載の製造方法。
- 水素供与体が、水素である請求項4~6のいずれかに記載の製造方法。
- 請求項1~3のいずれかに記載の固相担持ルテニウム錯体を含む還元用触媒。
- 還元用触媒が、不斉還元用触媒である請求項9に記載の触媒。
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