CN110494412A - 手性金属配合物 - Google Patents
手性金属配合物 Download PDFInfo
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- CN110494412A CN110494412A CN201880024017.7A CN201880024017A CN110494412A CN 110494412 A CN110494412 A CN 110494412A CN 201880024017 A CN201880024017 A CN 201880024017A CN 110494412 A CN110494412 A CN 110494412A
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- Prior art keywords
- metal complex
- formula
- chiral metal
- chiral
- formulas
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- 150000004696 coordination complex Chemical class 0.000 title claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 150000002576 ketones Chemical class 0.000 claims abstract description 17
- 150000001768 cations Chemical group 0.000 claims abstract description 9
- 230000007935 neutral effect Effects 0.000 claims abstract description 9
- 150000002466 imines Chemical class 0.000 claims abstract description 5
- 150000002923 oximes Chemical class 0.000 claims abstract description 5
- 239000011572 manganese Substances 0.000 claims description 23
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 21
- 229910052751 metal Inorganic materials 0.000 claims description 21
- 239000002184 metal Substances 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 19
- 229910052748 manganese Inorganic materials 0.000 claims description 19
- 150000001412 amines Chemical class 0.000 claims description 14
- 150000004698 iron complex Chemical class 0.000 claims description 14
- 239000003446 ligand Substances 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- GWLJTAJEHRYMCA-UHFFFAOYSA-N phospholane Chemical compound C1CCPC1 GWLJTAJEHRYMCA-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- -1 and R4For CO Chemical class 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052742 iron Chemical group 0.000 claims description 7
- AOWPVIWVMWUSBD-RNFRBKRXSA-N [(3r)-3-hydroxybutyl] (3r)-3-hydroxybutanoate Chemical compound C[C@@H](O)CCOC(=O)C[C@@H](C)O AOWPVIWVMWUSBD-RNFRBKRXSA-N 0.000 claims description 6
- 230000000737 periodic effect Effects 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000002577 pseudohalo group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- 239000000758 substrate Substances 0.000 description 30
- 239000003054 catalyst Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 239000007787 solid Substances 0.000 description 11
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000000956 alloy Substances 0.000 description 4
- 229910045601 alloy Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- LREGBYAVKWWAIK-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-trimethylsilylethanamine Chemical compound ClCCN([Si](C)(C)C)CCCl LREGBYAVKWWAIK-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000000769 gas chromatography-flame ionisation detection Methods 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 230000008570 general process Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012263 liquid product Substances 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000607 proton-decoupled 31P nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VMLOJVKKOABMEO-UHFFFAOYSA-N 2,2'-bis[(s-1,1'-binaphthyl-2,2'-dimethyl)phosphino]diethylamine Chemical compound C1C2=CC=C3C=CC=CC3=C2C(C2=CC=CC=C2C=C2)=C2CP1CCNCCP(C1)CC2=CC=C(C=CC=C3)C3=C2C2=C1C=CC1=CC=CC=C21 VMLOJVKKOABMEO-UHFFFAOYSA-N 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005046 Chlorosilane Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- KOOADCGQJDGAGA-UHFFFAOYSA-N [amino(dimethyl)silyl]methane Chemical compound C[Si](C)(C)N KOOADCGQJDGAGA-UHFFFAOYSA-N 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- NHFDIUPJVYYTLG-UHFFFAOYSA-N carbononitridic isocyanide Chemical compound [C-]#[N+]C#N NHFDIUPJVYYTLG-UHFFFAOYSA-N 0.000 description 1
- 210000000080 chela (arthropods) Anatomy 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- 235000019628 coolness Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 150000002012 dioxanes Chemical class 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- 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
- C07C29/145—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 with hydrogen or hydrogen-containing gases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D307/44—Furfuryl alcohol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D309/06—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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Abstract
本发明包括式(I)的新型手性金属配合物，其中M、PR2、R3和R4如说明书中所概述，它的立体异构体，其为中性配合物或带有合适反离子的配位阳离子形式的。所述手性金属配合物可用于不对称反应中，特别是用于酮、亚胺或肟的不对称还原中。
Description
本发明涉及具有下式的新型手性金属配合物
其中M、PR2、R3和R4如下文所定义，以及它的立体异构体，其为中性配合物或带有合适反离子的配位阳离子形式的。
本发明还涉及用于制备手性金属配合物的方法及其在不对称反应中的用途，特别是在C＝X双键即酮(C＝O)、α-酮酯或β-酮酯(α：-(C＝O)-(C＝O)-OR或β：-(C＝O)-CR2-(C＝O)-OR)、亚胺(-C＝N-R)或肟(-C＝N-OH)的不对称还原中的用途。
用于不对称反应诸如不对称氢化的催化剂领域的研究倾向于从铂族金属催化剂转向环保的非铂族金属催化剂。(P.G.Anderson等人,J.Am.Chem.Soc.2017,139,1346；R.H.Morris等人,ACS Catal.2017,7,316)。
本发明的目的是提供手性金属配合物催化剂，其既环保又具有高对映选择性和转化率。
利用以下化合物可达到该目的：式I的新型手性金属配合物
其中
表示虚线键(a)或楔形键(b)
a)b)
M为选自元素周期表的锰族或铁族的金属；
PR2为
其中R5和R6彼此独立地为C1-4烷基或芳基；或
其中R7和R8彼此独立地为C1-4烷基；
R3为CO、卤素或氢，并且
R4为CO、卤素或H-BH3；
和它的立体异构体，其为中性配合物或带有合适反离子的配位阳离子形式的。
除非另外定义，否则本文中使用的所有技术和科学术语所具有的含义与本发明所属领域普通技术人员通常理解的含义相同。尽管在本发明的实践或测试中，可使用与本文所述的那些方法和材料类似或等同的方法和材料，但下文描述了合适的方法和材料。
术语“手性”表示与镜像不重叠的能力，而术语“非手性”是指能够与其镜像重叠的实施方案。手性分子具有光学活性，即它们具有旋转平面偏振光的平面的能力。当化学结构中存在手性中心时，意指与该手性中心相关联的所有立体异构体都包括在本发明中。
术语“手性”意味着分子能够以光学纯对映体、对映体混合物、光学纯非对映体或非对映体混合物的形式存在。
在本发明的一个优选实施方案中，术语“手性”表示光学纯对映体或光学纯非对映体。
术语“立体异构体”表示具有相同的分子连接性和键多重性但其原子在空间中的排列不同的化合物。
术语“非对映体”表示具有两个或更多个手性中心并且其分子并非彼此镜像的立体异构体。非对映体具有不同的物理性质，例如熔点、沸点、光谱特性和反应性。
术语“对映体”表示化合物的两种立体异构体，它们是彼此不可重叠的镜像。
在本文所提供的结构式中，虚线键(a)表示取代基在纸平面下方，楔形键(b)表示取代基在纸平面上方。
a)b)
螺旋键(c)表示两种选项，即虚线键(a)或楔形键(b)。
c)
术语“C-1-4烷基”表示具有1至4个碳原子的单价直链或支链饱和烃基。C1-4烷基的示例包括甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基。
术语“卤素”表示氟、氯、溴或碘。
术语“拟卤素”表示卤素的类似物，其化学性质与卤素的化学性质类似。拟卤素的示例包括氰基、异氰化物、氰酸酯或异氰酸酯。
术语“芳基”表示包含6至10个碳环原子的单价芳族碳环单环体系或双环体系，其任选地可被取代。芳基部分的示例包括苯基和萘基。苯基为优选的芳基基团。
与术语“芳基”有关的术语“任选取代”表示芳基基团可以不被取代或被一个或多个取代基取代，该取代基独立地选自C1-4烷基、C1-4烷氧基或卤素。
M代表元素周期表的锰族或铁族的金属。
合适的锰族金属为锰或铼，优选地为锰。
合适的铁族金属为铁、钌或锇，优选地为铁。
在本发明的一个优选实施方案中，金属M选自元素周期表的锰族或铁族，并且更优选地，金属M选自锰或铁。
PR2代表配体
其中R5和R6彼此独立地为C1-4烷基或芳基，优选地为C1-4烷基或苯基，更优选地为C1-4烷基，甚至更优选地为甲基；或
其中R7和R8彼此独立地为C1-4烷基，更优选地为甲基。
PR2特别地为式IIa1的配体
其中R5和R6如上所述，但是其中R5和R6优选地为C1-4烷基，更优选地为甲基。
更特别地，PR2为式IIa2'或IIa2”的配体
其中R5和R6如上所述，但是优选地为C1-4烷基，更优选地为甲基。
在本发明的一个优选实施方案中，手性金属配合物具有式Ia
其中M、PR2、R3和R4如上所述，其为中性配合物或带有合适反离子的配位阳离子形式的。
在采用锰作为优选的金属M时，手性锰配合物具有式Ib
其中PR2、R3和R4如上所述，其为中性配合物或带有合适反离子的配位阳离子形式的，更优选地手性锰配合物具有式Id
其中PR2如上所述，并且X为卤素或拟卤素。
X优选地代表卤素，更优选地代表溴或氯，甚至更优选地代表溴。
同样，以铁作为优选的金属M时，手性铁配合物具有式Ic
其中PR2、R3和R4如上所述，更优选地手性铁配合物具有式Ie
其中PR2如上所述。
最优选的手性金属配合物具有式If
或式Ig
本发明还包括制备式I的手性金属配合物的方法，该方法包括式III的双(磷杂环戊烷基乙基)胺衍生物与金属盐的反应
其中，PR2如上所述。适用于反应的金属盐在很大程度上取决于所用的金属M。
式III的双(磷杂环戊烷基乙基)胺衍生物可按照本领域中已知的方法由相应的膦HPR2开始合成。
因此，对于其中PR2代表如下配体的膦
根据M.J.Burk,J.E.Feaster,R.L.Harlow,Tetrahedron:Asymmetry 1991,2,569-592所述，可通过二甲基磷杂环戊烷与双(2-氯乙基)三甲基甲硅烷基胺的反应，合成式III的双(磷杂环戊烷基乙基)胺衍生物，其中R5和R6为甲基。
式III的双(磷杂环戊烷基乙基)胺衍生物(其具有下式的膦配体PR2)
可例如从Sigma-Aldrich商购获得(CAS号791630-00-7)。
对于具有下述配体PR2的膦
其中R7和R8如上所述，可根据M.J.Burk,J.E.Feaster,R.L.Harlow,Tetrahedron:Asymmetry 1991,2,569-592所述，通过具有式IIc的配体的膦与双(2-氯乙基)三甲基甲硅烷基胺的反应，以类似于式IIa的配体PR2的方式实现。
式III的双(磷杂环戊烷基乙基)胺衍生物的合成可根据M.J.Burk,J.E.Feaster,R.L.Harlow,Tetrahedron:Asymmetry 1991,2,569-592所述来实现。
式Id的手性金属配合物的制备
其中PR2如上所述，包括式III的双(磷杂环戊烷基乙基)胺衍生物与Mn(CO)5X的反应
其中，PR2如上所述，在Mn(CO)5X中，X-为卤素或拟卤素，优选地为卤素，更优选地为氯或溴，甚至更优选地为溴。
该反应有利地在惰性气氛下，于合适的有机溶剂中以及20℃至150℃优选地为80℃至110℃的反应温度下进行。
合适的溶剂为非极性溶剂，诸如芳烃，如甲苯或苯。
可通过标准技术分离配合物，并且可通过结晶将其进一步纯化。
式Ie的手性金属配合物的制备
包括使式III的双(磷杂环戊烷基乙基)胺衍生物
与FeX2和一氧化碳进行反应以形成式IV的铁配合物中间体
在式III中，PR2如上所述，在FeX2中，X为卤素
以及随后用合适的氢化物形成剂使所述铁配合物中间体转化为式Ie的手性金属配合物。
FeX2优选地为氯化铁或溴化铁，更优选地为溴化铁。
式III的双(磷杂环戊烷基乙基)胺衍生物与FeX2的反应通常发生在合适的有机溶剂诸如极性非质子溶剂如四氢呋喃中以及0℃至50℃优选地为20℃至30℃的反应温度下，并且反应时间为2h至8h。
随后与一氧化碳反应形成式IV的中间体可发生在0℃至50℃优选地为20℃至30℃的反应温度下，并且反应时间为0.5h至6h。
通过除去溶剂并用合适的溶剂诸如乙醇洗涤粗中间体化合物，可轻松分离中间体。
式IV的手性铁配合物中间体
是现有技术中未知的化合物，因此也是本发明的一个实施方案，在式IV中，PR2如上所述并且X为卤素。
在一个更优选的实施方案中，X为氯或溴，更优选地为溴。
PR2特别地为式IIa1的配体
其中R5和R6如上所述，但是其中R5和R6优选地为C1-4烷基，更优选地为甲基。
更特别地，PR2为式IIa2'或IIa2”的配体
其中R5和R6如上所述，但是优选地为C1-4烷基，更优选地为甲基。
最优选的手性铁配合物中间体具有式IV，其中X为溴并且PR2具有式IIa2'，其中R5和R6为甲基。
用于使式IV的手性铁配合物中间体转化为式Ie的手性金属配合物的合适的氢化物形成剂可选自配位金属氢化物，如氢化铝锂、氢化二异丁基铝或硼氢化钠，优选硼氢化钠。
反应通常发生在合适的有机溶剂诸如非极性溶剂如甲苯中以及0℃至50℃的反应温度下。
通过除去溶剂并用合适的溶剂例如正庚烷洗涤粗配合物，可分离期望的铁配合物。
在本发明的另一实施方案中，上述手性金属配合物可用于催化不对称反应，特别是不对称还原，更特别地是C＝X双键即酮(C＝O)、α-酮酯或β-酮酯(α：-(C＝O)-(C＝O)-OR或β：-(C＝O)-CR2-(C＝O)-OR)、亚胺(-C＝N-R)或肟(-C＝N-OH)的不对称还原。
在本发明的一个更优选的实施方案中，上述手性金属配合物可用于催化C＝X双键即酮、酮酯、亚胺或肟的不对称氢化，特别是催化酮的不对称氢化。
手性金属配合物在具有C＝X官能团的化合物的各种底物上具有活性。
因此，对于酮，二烷基酮、芳基烷基酮、环烷基烷基酮、α-酮酯和β-酮酯、环烷酮、杂环基烷基酮或甚至含有酮基团的杂环化合物都是合适的底物。
不对称氢化的反应条件在很大程度上取决于所选的手性金属配合物和底物，但是在原则上，反应条件对本领域的技术人员来讲是已知的。
在用优选的式Id的锰配合物对酮进行不对称氢化的典型过程中，在惰性气氛以及碱存在下，将配合物溶于合适的有机溶剂中。然后加入酮底物，通常在高压釜中于升高的温度和5bar至100bar优选地为10bar至60bar的氢气压力下进行氢化。
在用优选的式Ie的铁配合物对酮进行不对称氢化的典型过程中，在惰性气氛下，将配合物溶于合适的有机溶剂中。然后加入酮底物，通常在高压釜中于升高的温度和5bar至100bar优选地为10bar至60bar的氢气压力下进行氢化。以下实例将进一步说明本发明。
实施例：
缩写：
X的X射线晶体结构分析：在Bruker Kappa APEX II Duo衍射仪上采集数据。结构通过直接法(SHELXS-97:Sheldrick,G.M.Acta Cryst.2008,A64,112.)进行解析，并通过F2(SHELXL-2014:G.M.Sheldrick,Acta Cryst.2015,C71,3.)上的全矩阵最小二乘法进行修正。利用XP(Bruker AXS)进行图形表示。
1.配体合成：
1.1(2R,5R)-2,5-二甲基磷杂环戊烷的合成
根据报道的方法(T.Hammerer,A.W.Braun,A.Salzer,G.Franció,W.Leitner,Synthesis 2012,44,2793-2797)合成标题化合物。
向异丙醇冷却浴(-79℃)冷却的(R,R)-2,5-二甲基-1-(三甲基甲硅烷基)磷杂环戊烷(9.42g，50.0mol)溶液，逐滴加入MeOH(1.63g，51.0mol)。将所得溶液加热至室温，并搅拌过夜。将溶液加热至高达60℃，使副产物冷凝到另一个Schlenk烧瓶中。分离呈无色液体的产物，收率为95％(5.52g，47.5mmol)。
1.2双(2-氯乙基)三甲基甲硅烷基胺的合成
按照报道的方法(A.A.Danopoulos,A.R.Willis,P.G.Edwards,Polyhedron 1990,9,2413-2418)合成标题化合物。
向100mL Et2O、0.25mL DMSO和三乙胺(17.0g，168.0mmol)中的搅拌和冷却(0℃)的双(2-氯乙基)胺盐酸盐(10g，56.0mmol)悬浮液中，在0℃下，于半小时内逐滴加入三甲基氯硅烷(21.3g，196mmol)。在0℃下将该溶液搅拌1小时，加热至室温，并进一步搅拌3-5天。对该溶液进行过滤，真空除去液体部分的挥发物，得到呈黄色粘稠液体的产物(9.96g，46.5mmol，收率为83％)。
1.3双(2-((2R,5R)-2,5-二甲基磷杂环戊烷基乙基))胺的合成
参照报道的方法(M.J.Burk,J.E.Feaster,R.L.Harlow,Tetrahedron.Asymmetry1991,2,569-592)合成标题化合物。
将(2R,5R)-2,5-二甲基磷杂环戊烷(6.9g，0.059mmol)溶于80mL正己烷中，并冷却至-79℃。向该溶液中逐滴加入正丁基锂(2.5M，溶于正己烷中，25mL，62.5mmol)。在此温度下将溶液搅拌半小时，加热至室温，将所得的淡黄色溶液进一步搅拌5小时。加入10mL THF，并使溶液再次冷却至-79℃。逐滴加入稀释于10mL THF中的6.32g(29.5mmol)双(2-氯乙基)三甲基甲硅烷基胺，同时沉淀出白色固体。在室温下，将浅黄色悬浮液搅拌16h。然后加入30mL水和60mL TBAF(1M THF溶液，60mmol)，将所得的两相体系进一步搅拌3-5天。真空除去大部分有机溶剂，并用Et2O从水相对产物萃取三次。用MgSO4干燥有机层，过滤，除去液体部分的挥发物，并对黄色产物进行真空干燥(6.76g，22.4mmol，收率为71％)。使用钳形配体而不经进一步纯化。
1H NMR(400.13MHz；CD3Cl)：δ＝1.08-1.12(dd,6H,CH 3,J＝7.2Hz)；1.16-1.23(dd,6H,CH 3,J＝7.2Hz；m,2H,CH 2)；1.34-1.47(m,4H,CH 2)；1.61-1.68(m,2H,CH 2)；1.84-1.92(m,2H,CH)；1.93-2.02(m,2H,CH 2)；2.03-2.15(m,4H,CH 2,CH)；2.62-2.78(m,4H,CH 2)，3.8(br,1H,NH)。
31P NMR(121.5MHz；CD3Cl)：δ＝-5.2ppm。
2.配合物合成
2.1锰配合物合成
向甲苯(20mL)中的[MnBr(CO)5](275mg，1mmol)悬浮液中，加入双(2-((2R,5R)-2,5-二甲基磷杂环戊烷基乙基))胺(331.5mg，1.1mmol，溶于2mL甲苯中)。将[MnBr(CO)5]溶解，将溶液加热至100℃并在氩气流下进一步搅拌20h。将反应混合物冷却至室温并真空浓缩，得到其中包含红色内含物的黄色固体。用5mL戊烷对粗固体洗涤三次，得到纯净的黄色/橙色固体(359.5mg，72.4mmol，收率为72％)。
31P{1H}NMR(122MHz,C6D6)：δ＝97.14。
IR-ATR(固体)[cm-1]：2009(s,CO)，1908(s,CO)，1821(s,CO)。
EA％ber.(gef)C17H38BrMnNO3P2，M＝520.27g/mol：C 43.86(44.97)；H 6.39(6.61)N 2.69(2.74)。
2.2铁配合物合成
a)前体的合成
将2.07g双(2-((2R,5R)-2,5-二甲基磷杂环戊烷基乙基))胺(6.8mmol)溶于30mLTHF中。然后加入溶于20mL THF中的FeBr2·THF溶液(2.84g,6.8mmol)。在室温下将所得的棕色/黄色溶液搅拌过夜。与CO反应三小时，形成蓝色固体。真空除去溶剂，并用5mL EtOH洗涤所得的粗固体，得到纯化合物，其收率为63％(2.35g，4.3mmol)。
1H NMR(400.13MHz；CD3Cl)：δ＝1.11-1.16(m,6H,CH3)；1.22-1.38(m,3H,P-CH2)；1.42-1.52(m,2H,P-CH2)；1.59-1.78(m,9H,2x CH3；P-CH2)；1.80-1.90(m,1H,P-CH2)；1.99-2.16(m,3H,P-CH)；2.29-2.36(m,1H,P-CH)；2.37-2.45(m,1H,P-CH)；2.54-2.78(dd,2H,N-CH2)；2.82-2.92(m,1H,N-CH2)；2.94-3.04(m,2H,P-CH)；3.14-3.26(m,1H,N-CH2)；4.32-4.44(br,1H,NH)。
31P{1H}NMR(122MHz,C6D6)：δ＝95.91(d,JPP＝174.19Hz)，98.54(d,JPP＝174.19)。
IR-ATR(固体)[cm-1]：1935(s,CO)。
b)铁配合物Ie的合成
将690mg IV(1.27mmol)溶于20mL苯或甲苯中。将新制备的NaBH4溶液(383mg，10.12mmol，溶于20mL EtOH中)逐滴加入溶液中，则会直接观察到显著的气体逸出。将溶液搅拌3-5h后，除去溶剂，并对剩余的固体进行真空干燥。用苯或甲苯(总共40mL)萃取产物，然后真空除去溶剂。用10mL正庚烷洗涤粗固体三次，得到预期的产物，其收率为80％(403mg)。
1H-NMR(300K,C6D6,400.13MHz)：δ＝-19.20(t，1H，Fe-H，2JHP＝51.85Hz(次要异构体))，-18.80(t，1H，Fe-H，2JHP＝51.75Hz(主要异构体))，-2.77(bs,4H,HBH3)，0.95(m,3H,CH3)，1.15(m,3H,CH-CH2)，1.25(m，5H，CH3和P-CH2和CH-CH2)，1.32(m,1H,CH-CH2)，1.41(m,3H,CH3)，1.51(m,2H,N-CH2)，1.58(m,1H,CH)，1.66(m,1H,P-CH2)，1.73(m，6H，CH3，P-CH2和CH-CH2)，1.91(m，4H，CH-CH2和CH)，2.08(m,1H,P-CH2)，2.27(m,1H,CH)，2.62(m，3H，CH和N-CH2)，3.76(m,1H,N-H)。
31P-NMR-主要异构体(300K,C6D6,100.616MHz)：δ＝109.18(d,1P,2JPP＝122.93Hz)，107.02(d,1P,2JPP＝120.75Hz)。
31P-NMR-次要异构体(300K,C6D6,100.616MHz)：δ＝114.41(d,1P,2JPP＝116.87Hz)，104.98(d,1P,2JPP＝116.64Hz)。
IR-ATR(固体)[cm-1]：1894(s,CO)。
3.不对称氢化结果
3.1用实施例2.1的锰配合物对酮或酮酯进行氢化
一般过程：
使用分子氢的所有催化氢化实验均在Parr Instruments高压釜(300mL)中进行，以内部合金板推进高压釜，该内部合金板包括多达8个同样的反应瓶(4mL)，这些反应瓶配备瓶盖和刺穿隔垫的针。
代表性实验：
在氩气气氛下，向小瓶中装入实施例2.1的锰配合物和碱，该锰配合物和碱溶于2mL干溶剂中。稍微搅拌所得的红色溶液，然后加入酮或酮酯(0.5或1mmol)。将小瓶置于合金板中，该合金板随后会放入高压釜内。密封后，用氢气对高压釜吹扫5次，然后加压至30bar并加热至期望的温度。然后，将高压釜冷却至室温，减压，并利用GC-FID或HPLC以及GC-MS对反应混合物进行分析。使用硅胶作为固定相，并以正戊烷/乙酸乙酯或正戊烷/丙酮混合物作为洗脱剂，通过柱色谱法进行产物分离。
各个反应条件：
[a]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，50℃，EtOH(1.5mL)
[b]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，70℃，EtOH(1.5mL)
[c]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，50℃，甲苯(1.5mL)
[d]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，50℃，iPrOH(1.5mL)
[e]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，50℃，iPrOH(1.5mL)
[f]1mol％催化剂，5mol％KOtBu，0.5mmol底物，30bar，4-5h，40℃，叔戊醇(1.5mL)
[g]1mol％催化剂，5mol％KOtBu，0.5mmol底物，30bar，16h，50℃，甲苯(1.5mL)
[h]2mol％催化剂，5mol％KOtBu，0.5mmol底物，30bar，8h，100℃，二噁烷(1.5mL)
[i]1mol％催化剂，5mol％KOtBu，1mmol底物，30bar，4h，30℃，1,4-二氧六环(2mL)
[j]1mol％催化剂，5mol％KOtBu，1mmol底物，30bar，4h，40℃，叔戊醇(2mL)
[k]1mol％催化剂，5mol％KOtBu，1mmol底物，30bar，4h，80℃，叔戊醇(2mL)
[l]2mol％催化剂，5mol％KOtBu，1mmol底物，30bar，4h，50℃，甲苯(2mL)
[m]2mol％催化剂，5mol％KOtBu，1mmol底物，30bar，4h，80℃，叔戊醇(2mL)
[n]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，3h，70℃，iPrOH(1.5mL)
[o]2mol％催化剂，5mol％NaOtBu，0.5mmol底物，30bar，1h，50℃，iPrOH(1mL)
SP＝副产物(双键的氢化)
表1：
3.2用实施例2.2的铁配合物对酮或酮酯进行氢化
一般过程：
使用分子氢的所有催化氢化实验均在Parr Instruments高压釜(300mL)中进行，以内部合金板推进高压釜，该内部合金板包括多达8个同样的反应瓶(4mL)，这些反应瓶配备瓶盖和刺穿隔垫的针。
代表性实验：
在氩气气氛下，向小瓶中装入实施例2.2的铁配合物，该铁配合物溶于2mL干溶剂中。稍微搅拌所得的黄色溶液，然后加入酮或酮酯(0.5或1mmol)。将小瓶置于合金板中，该合金板随后会放入高压釜内。密封后，用氢气对高压釜吹扫5次，然后加压至30bar并加热至期望的温度。然后，将高压釜冷却至室温，减压，并利用GC-FID或HPLC以及GC-MS对反应混合物进行分析。使用硅胶作为固定相，并以正戊烷/乙酸乙酯或正戊烷/丙酮混合物作为洗脱剂，通过柱色谱法进行产物分离。
各个反应条件：
[a]1mol％催化剂，0.5mmol底物，30bar，3h，30℃，CH2Cl(1.5mL)
[b]3mol％催化剂，0.5mmol底物，30bar，3h，70℃，iPrOH(1.5mL)
[c]2mol％催化剂，0.5mmol底物，30bar，2h，50℃，EtOH(1.5mL)
[d]1mol％催化剂，0.5mmol底物，30bar，3h，70℃，iPrOH(1.5mL)
[f]1mol％催化剂，1mmol底物，30bar，22h，40℃，正庚烷(1.5mL)
[g]1mol％催化剂，1mmol底物，30bar，3h，30℃，EtOH(2mL)
[h]1mol％催化剂，1mmol底物，30bar，6h，30℃，EtOH(2mL)
[i]1mol％催化剂，1mmol底物，30bar，6h，60℃，EtOH(2mL)
[j]1mol％催化剂，1mmol底物，30bar，6h，30℃，EtOH(2mL)
[k]3mol％催化剂，1mmol底物，30bar，3h，70℃，THF(2mL)
SP＝副产物(双键的氢化)
表2：
Claims (19)
1.下式的手性金属配合物
其中
表示虚线键(a)或楔形键(b)
a)b)
M为选自元素周期表的锰族或铁族的金属；
PR2为
其中R5和R6彼此独立地为C1-4烷基或芳基；或
其中R7和R8彼此独立地为C1-4烷基；
R3为CO、卤素或氢，并且
R4为CO、卤素或H-BH3；
以及它的立体异构体，其为中性配合物或带有合适反离子的配位阳离子形式的。
2.下式的手性金属配合物
其中
表示虚线键(a)或楔形键(b)
a)b)
M为选自元素周期表的锰族或铁族的金属；
PR2为
其中R5和R6彼此独立地为C1-4烷基或芳基；或
其中R7和R8彼此独立地为C1-4烷基；
R3为CO或氢，并且
R4为CO或H-BH3；
以及它的立体异构体，其为中性配合物或带有合适反离子的配位阳离子形式的。
3.根据权利要求1或2所述的手性金属配合物，其中所述金属M为选自元素周期表的锰族或铁族的金属。
4.根据权利要求1至3中任一项所述的手性金属配合物，其中所述金属M选自锰或铁。
5.根据权利要求1至4中任一项所述的手性金属配合物，其中PR2为式IIa1的配体
其中R5和R6如上所述，但是R5和R6优选地为C1-4烷基。
6.根据权利要求1至5中任一项所述的手性金属配合物，其中PR2为式IIa2'或式IIa2”的配体
其中R5和R6如上所述，但是优选地为C1-4烷基。
7.根据权利要求1至6中任一项所述的手性金属配合物，其具有式Ia
其中M、PR2、R3和R4如上所述，其为中性配合物或带有合适反离子的配位阳离子形式的。
8.根据权利要求1至7中任一项所述的手性金属配合物，其具有式Ib
其中PR2、R3和R4如上所述，其为中性配合物或带有合适反离子的配位阳离子形式的。
9.根据权利要求1至7中任一项所述的手性金属配合物，其具有式Ic
其中PR2、R3和R4如上所述。
10.式Id的根据权利要求1至8中任一项所述的手性金属配合物；
其中PR2如上所述，并且X为卤素或拟卤素。
11.式Ie的根据权利要求1至7和权利要求9中任一项所述的手性金属配合物；
其中PR2如上所述。
12.式If的根据权利要求1至8和权利要求10中任一项所述的手性金属配合物；
13.式Ig的根据权利要求1至7、权利要求9和权利要求11中任一项所述的手性金属配合物
14.制备式I的手性金属配合物的方法，所述方法包括式III的双(磷杂环戊烷基乙基)胺衍生物与金属盐的反应
其中，PR2如上所述。
15.制备式Id的手性金属配合物的方法
其中，PR2如上所述，所述方法包括式III的双(磷杂环戊烷基乙基)胺衍生物
其中，PR2如上所述
与Mn(CO)5X-的反应，
在所述Mn(CO)5X-中，X-为卤素或拟卤素，优选地为卤素。
16.制备式Ie的手性金属配合物的方法
其中，PR2如上所述
所述方法包括使式III的双(磷杂环戊烷基乙基)胺衍生物
与FeX2和一氧化碳进行反应以形成式IV的铁配合物中间体
在所述式III中，PR2如上所述，在所述FeX2中，X为卤素
在所述式IV中，PR2如上所述并且X为卤素；
以及随后用合适的氢化物形成剂使所述铁配合物中间体转化为式Ie的手性金属配合物。
17.式IV的手性铁配合物中间体
其中PR2如上所述并且X为卤素。
18.权利要求1至13所述的手性金属配合物在催化不对称反应中的应用。
19.根据权利要求18所述的应用，其中所述不对称反应为不对称还原，特别是C＝X双键即酮、酮酯、亚胺或肟的不对称还原。
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| IL269827A (en) | 2019-11-28 |
| AU2018250840A1 (en) | 2019-08-22 |
| BR112019018979A2 (pt) | 2020-04-14 |
| AU2018250840B2 (en) | 2021-06-24 |
| CA3052387A1 (en) | 2018-10-18 |
| KR102636763B1 (ko) | 2024-02-14 |
| US20200040021A1 (en) | 2020-02-06 |
| IL269827B2 (en) | 2023-04-01 |
| EP3609859A1 (en) | 2020-02-19 |
| BR112019018979B1 (pt) | 2023-01-10 |
| IL269827B (en) | 2022-12-01 |
| EP3609859B1 (en) | 2022-04-27 |
| KR20190134637A (ko) | 2019-12-04 |
| JP7267932B2 (ja) | 2023-05-02 |
| MX2019012177A (es) | 2019-12-19 |
| US11124532B2 (en) | 2021-09-21 |
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