CN1289515C - 不对称(转移)氢化催化剂 - Google Patents
不对称(转移)氢化催化剂 Download PDFInfo
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- CN1289515C CN1289515C CNB018123910A CN01812391A CN1289515C CN 1289515 C CN1289515 C CN 1289515C CN B018123910 A CNB018123910 A CN B018123910A CN 01812391 A CN01812391 A CN 01812391A CN 1289515 C CN1289515 C CN 1289515C
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- Prior art keywords
- hydrogenation
- asymmetric
- catalyzer
- atom
- group
- Prior art date
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- 238000005984 hydrogenation reaction Methods 0.000 title abstract description 43
- 239000003054 catalyst Substances 0.000 title abstract description 20
- 238000012546 transfer Methods 0.000 title abstract description 18
- 239000003446 ligand Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 27
- 239000010948 rhodium Substances 0.000 claims abstract description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 19
- 150000002466 imines Chemical class 0.000 claims abstract description 11
- 150000002576 ketones Chemical class 0.000 claims abstract description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 8
- 125000004437 phosphorous atom Chemical group 0.000 claims abstract description 8
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 7
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 7
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 7
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 7
- 150000003624 transition metals Chemical class 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- 239000000852 hydrogen donor Substances 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 150000002923 oximes Chemical class 0.000 claims abstract description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 4
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 150000001336 alkenes Chemical class 0.000 claims description 10
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 10
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 239000002608 ionic liquid Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000002002 slurry Substances 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 52
- 239000000460 chlorine Substances 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 229910052717 sulfur Inorganic materials 0.000 description 23
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- -1 OAc Inorganic materials 0.000 description 19
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- 229910015892 BF 4 Inorganic materials 0.000 description 16
- 238000003756 stirring Methods 0.000 description 13
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 11
- 230000009466 transformation Effects 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 238000007872 degassing Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 229910020366 ClO 4 Inorganic materials 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000012018 catalyst precursor Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical compound OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000004679 31P NMR spectroscopy Methods 0.000 description 3
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229910021115 PF 6 Inorganic materials 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- LXJOYRVJPWDJBZ-UHFFFAOYSA-N (2-acetamido-3-hydroxyphenyl)arsonic acid Chemical compound OC=1C(=C(C=CC1)[As](O)(O)=O)NC(C)=O LXJOYRVJPWDJBZ-UHFFFAOYSA-N 0.000 description 2
- NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 2
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 2
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 2
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 2
- DBZAKQWXICEWNW-UHFFFAOYSA-N 2-acetylpyrazine Chemical compound CC(=O)C1=CN=CC=N1 DBZAKQWXICEWNW-UHFFFAOYSA-N 0.000 description 2
- IGJQUJNPMOYEJY-UHFFFAOYSA-N 2-acetylpyrrole Chemical compound CC(=O)C1=CC=CN1 IGJQUJNPMOYEJY-UHFFFAOYSA-N 0.000 description 2
- WEGYGNROSJDEIW-UHFFFAOYSA-N 3-Acetylpyridine Chemical compound CC(=O)C1=CC=CN=C1 WEGYGNROSJDEIW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 2
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 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 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HYSOPXHRAHXSFM-MRVPVSSYSA-N [(1s)-1-methylcyclohexa-2,4-dien-1-yl]methanamine Chemical compound NC[C@@]1(C)CC=CC=C1 HYSOPXHRAHXSFM-MRVPVSSYSA-N 0.000 description 2
- JAZCEXBNIYKZDI-UHFFFAOYSA-N [Ir+] Chemical compound [Ir+] JAZCEXBNIYKZDI-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960003328 benzoyl peroxide Drugs 0.000 description 2
- AKGGYBADQZYZPD-UHFFFAOYSA-N benzylacetone Chemical compound CC(=O)CCC1=CC=CC=C1 AKGGYBADQZYZPD-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 2
- NQBWNECTZUOWID-QSYVVUFSSA-N cinnamyl cinnamate Chemical compound C=1C=CC=CC=1\C=C/C(=O)OC\C=C\C1=CC=CC=C1 NQBWNECTZUOWID-QSYVVUFSSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000002736 metal compounds Chemical class 0.000 description 2
- 125000005395 methacrylic acid group Chemical group 0.000 description 2
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HYSOPXHRAHXSFM-UHFFFAOYSA-N (1-methylcyclohexa-2,4-dien-1-yl)methanamine Chemical compound NCC1(C)CC=CC=C1 HYSOPXHRAHXSFM-UHFFFAOYSA-N 0.000 description 1
- LYXHWHHENVLYCN-QMDOQEJBSA-N (1z,5z)-cycloocta-1,5-diene;rhodium;tetrafluoroborate Chemical compound [Rh].F[B-](F)(F)F.C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 LYXHWHHENVLYCN-QMDOQEJBSA-N 0.000 description 1
- KYILORDWJFEQBS-RMKNXTFCSA-N (2e)-2-benzylidenebutanedioic acid Chemical compound OC(=O)C\C(C(O)=O)=C/C1=CC=CC=C1 KYILORDWJFEQBS-RMKNXTFCSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- KHHSXHXUQVNBGA-UHFFFAOYSA-N 1-(1h-pyrrol-3-yl)ethanone Chemical compound CC(=O)C=1C=CNC=1 KHHSXHXUQVNBGA-UHFFFAOYSA-N 0.000 description 1
- IBASEVZORZFIIH-UHFFFAOYSA-N 1-(9h-fluoren-2-yl)ethanone Chemical class C1=CC=C2C3=CC=C(C(=O)C)C=C3CC2=C1 IBASEVZORZFIIH-UHFFFAOYSA-N 0.000 description 1
- GCCKHXWBNPBUOD-UHFFFAOYSA-N 1-(furan-3-yl)ethanone Chemical compound CC(=O)C=1C=COC=1 GCCKHXWBNPBUOD-UHFFFAOYSA-N 0.000 description 1
- ZKMZPXWMMSBLNO-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-one Chemical compound C1CC2C(=O)CN1CC2 ZKMZPXWMMSBLNO-UHFFFAOYSA-N 0.000 description 1
- RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
- QQLIGMASAVJVON-UHFFFAOYSA-N 1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)C)=CC=CC2=C1 QQLIGMASAVJVON-UHFFFAOYSA-N 0.000 description 1
- GKDLTXYXODKDEA-UHFFFAOYSA-N 1-phenylbutan-2-one Chemical compound CCC(=O)CC1=CC=CC=C1 GKDLTXYXODKDEA-UHFFFAOYSA-N 0.000 description 1
- WMQUKDQWMMOHSA-UHFFFAOYSA-N 1-pyridin-4-ylethanone Chemical compound CC(=O)C1=CC=NC=C1 WMQUKDQWMMOHSA-UHFFFAOYSA-N 0.000 description 1
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- OECPUBRNDKXFDX-UHFFFAOYSA-N 2,2-dimethyl-1-phenylpropan-1-one Chemical group CC(C)(C)C(=O)C1=CC=CC=C1 OECPUBRNDKXFDX-UHFFFAOYSA-N 0.000 description 1
- AJKVQEKCUACUMD-UHFFFAOYSA-N 2-Acetylpyridine Chemical compound CC(=O)C1=CC=CC=N1 AJKVQEKCUACUMD-UHFFFAOYSA-N 0.000 description 1
- PPKAIMDMNWBOKN-UHFFFAOYSA-N 2-Oxo-4-phenylbutyric acid Chemical compound OC(=O)C(=O)CCC1=CC=CC=C1 PPKAIMDMNWBOKN-UHFFFAOYSA-N 0.000 description 1
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- PONXTPCRRASWKW-KBPBESRZSA-N diphenylethylenediamine Chemical compound C1([C@H](N)[C@@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-KBPBESRZSA-N 0.000 description 1
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- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
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- YUWFEBAXEOLKSG-UHFFFAOYSA-N hexamethylbenzene Chemical compound CC1=C(C)C(C)=C(C)C(C)=C1C YUWFEBAXEOLKSG-UHFFFAOYSA-N 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 1
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- 150000002825 nitriles Chemical class 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
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- TZMFJUDUGYTVRY-UHFFFAOYSA-N pentane-2,3-dione Chemical compound CCC(=O)C(C)=O TZMFJUDUGYTVRY-UHFFFAOYSA-N 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- XDAGXZXKTKRFMT-UHFFFAOYSA-N propan-2-imine Chemical compound CC(C)=N XDAGXZXKTKRFMT-UHFFFAOYSA-N 0.000 description 1
- 239000001327 prunus amygdalus amara l. extract Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000126 substance Substances 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
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 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
- 229930195735 unsaturated hydrocarbon Natural products 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
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium 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
- B01J31/18—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
- B01J31/1845—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 phosphorus
- B01J31/185—Phosphites ((RO)3P), their isomeric phosphonates (R(RO)2P=O) and RO-substitution derivatives thereof
- B01J31/1855—Triamide derivatives thereof
-
- 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
- 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
- C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
一种用通式MLaXbSc代表的不对称(转移)氢化用催化剂,其中M是过渡金属,选自铑和钌,X是反离子,S是配体,a介于0.5~3,b和c各自独立地介于0~2,L是一种手性配体,具有通式(1),其中Cn连同2个O-原子和P-原子一起形成一个取代或未取代的具有2~4个碳原子的环,R1和R2各自独立地代表H、任选取代的烷基、芳基、烷芳基或芳烷基基团,或者可与它们所键合的N-原子一起形成一个(杂环的)环。以及一种烯键不饱和化合物、酮、亚胺或肟衍生物在氢给体和催化剂存在下的不对称(转移)氢化方法,其中采用一种由通式MLaXbSc代表的催化剂,其中M是过渡金属,选自铑、铱和钌,X是反离子,S是配体,a介于0.5~3,b和c各自独立地介于0~2,其特征在于,L是一种手性配体,具有通式(1),其中Cn连同2个O-原子和P-原子一起形成一个取代或未取代的具有2~4个碳原子的环;R1和R2按上面的规定。
Description
本发明涉及一种包含过渡金属化合物和手性配体的不对称(转移)氢化催化剂。
此类催化剂可从G.Francio,F.Faraone和W.Leitner,《Angewandte Chemie.(应用化学)》2000国际版,39,1428~1430,得知。该出版物描述取代烯烃的不对称氢化用二齿膦磷酰胺化物(amidite)配体的应用,其对映体选择性最高达98.8%。
该已知催化剂的缺点是,使用的配体一般是通过许多反应步骤才制成的,其中的许多步骤收率又常常很低。这使得这些配体极其昂贵。这些含膦配体的另一个缺点是,它们对氧比较敏感,因此给它们的实际操作带来问题。
现在,本发明提供一种催化剂,由过渡金属催化剂与一种手性配体组成,其中该配体可在一个或两个步骤中由市售供应的原料简单地制成。
按照本发明,这是由一种用通式MLaXbSc代表的催化剂实现的,其中M是过渡金属,选自铑和钌,L是一种对映异构富集的手性单齿配体,具有通式(1),
其中Cn连同2个O-原子和P-原子一起形成一个取代或未取代的具有2~4个碳原子的环,R1和R2各自独立地代表H、任选取代的烷基、芳基、烷芳基或芳烷基基团,或者可与它们所键合的N-原子一起形成一个(杂环)环,X是反离子,S是配体,a介于0.5~3,b和c各自独立地介于0~2。优选的是,R1和R2各自独立地代表烷基基团,例如,1~6个碳原子的烷基基团,特别是1~3个碳原子,最优选C1和C2代表甲基基团。该烷基、芳基、芳烷基和烷芳基基团优选具有1~20个碳原子,并可任选地被例如,一个或多个羟基、烷氧基、腈或羧酸酯基团或者卤素取代。R1和/或R2可以是聚合物主链的一部分。
现已惊奇地发现,高对映体选择性可在烯烃、酮和亚胺的不对称氢化或不对称转移氢化中实现,只要采用可以简单方式制备的通式(I)的单齿配体。这就更加令人惊奇了,因为一般都认为,达到高对映体选择性需要二齿配体。本发明催化剂的另一个优点是,反应速率随着压力的增加而提高,同时不降低对映体选择性。结果,只需要较少用量催化剂或者可获得较快的反应。再一个优点是,本发明配体几乎对氧不敏感。在前手性化合物的不对称(转移)氢化中采用本发明催化剂,可获得对映异构富集的化合物,其中ee大于90%,尤其是大于95%,更尤其大于98%。
用通式MLaXbSc代表的本发明催化剂可以是中性、阴离子或阳离子性的。本发明催化剂可由预制的具有通式MLaXbSc的络合物组成。此类络合物可通过手性配体与催化剂前体之间的反应来制备。然而,优选的是,该催化剂就地生成,即,将手性配体加入到一种可包含容易被氢化反应去除的配体的催化剂前体的溶液中。需加入的旋光活性配体的数量,例如可介于0.5~5,优选1~3.5当量,相对于金属。优选的是,施加相对于催化剂中要求数量旋光活性配体稍许过量的旋光活性配体。旋光活性配体与金属在催化剂中的最佳比例随旋光活性配体以及随金属而异,可通过实验方便地确定。
该催化剂可在加入被作用物之前利用氢化(预氢化)来活化。现已发现,若本发明催化剂不经预处理,则达到的对映体选择性相同或甚至更高。
合适的催化剂前体的例子是(COD=1,5-环辛二烯);nbd=降冰片二烯;L=配体I;S=如下面规定的配体):
[Rh(COD)2Cl]2,[Rh(COD)2)]BF4,[Rh(nbd)2]BF4,[Rh(nbd)2]ClO4,[Ru(COD)Cl2]n,RhCl3.nH2O,Ru(OAc)3,RuCl3.nH2O.
预形成络合物的例子是RhL2(CH3OH)2BF4,Rh(COD)L2BF4,RuL2(OAc)2,RuL2Br2,Ru(甲基烯丙基)2L2、Ru(η-6-苯)L2Br2、Ru(η-5-环戊二烯基)L2Cl、RuL2Cl2、RuLSCl2、Ru(1,2-二苯基-1,2-二氨基乙烷)LCl2。
在通式(1)的手性配体L中,Cn和/或R1和/或R2是手性的或者是手性本体的一部分。Cn优选代表手性取代的C4链(具有4个任选取代的碳原子的链),其绝大多数是一种构型,例如,其对映体过量大于95%,特别是大于99%,更特别大于99.5%。优选的是,Cn连同两个氧原子和磷原子构成一个7-元环,其中4个碳原子两个一组地构成芳族基团或萘基基团的一部分。适合本发明的手性配体的例子是
不言而喻,在表示出一种对映异构体的地方,则其他对映异构体也类似地适用。
具有通式(I)的此种配体可按照,例如,Houben-Weyl有机化学方法,卷XII/2“有机磷化合物”,G.Thieme出版社,斯图加特,1964,部分2(第四版),pp.99~105中所述简单地制备。优选的制备方法基于HO-Cn-OH化合物与P(NMe2)3或P(NEt2)3(Me=甲基,Et=乙基)起反应,随后与R1R2NH起反应,优选在沸点大于80℃的溶剂如甲苯中进行。适合后一反应的催化剂例子是氯化铵、四唑或苯并咪唑鎓三氟甲磺酸化物(triflate)。HO-Cn-OH的例子是手性联萘酚,例如(R)-或(S)-1,1’-双(2-萘酚);手性双酚,例如,(R)-或(S)-6,6’-二甲氧基-2,2’-双酚;二醇,例如,(R,R)-或(S,S)-2,2-二甲基-1,3-二氧戊环-4,5-双(1,1-二苯基)甲醇(TADDOL),或者(S,R)或(R,S)-茚满-1,2-二醇;基于糖的1,2-二醇和1,3-二醇,例如,下列通式的二醇:
R1R2NH的例子是苄基胺、二苄基胺、二异丙基胺、(R)-或(S)-1-甲基-苄基胺、哌啶、吗啉、(R,R)-或(S,S)-双-(1-甲基苄基)胺。
第二个优选的制备方法基于HO-Cn-OH化合物与PCl3起反应,随后与R1R2NH起反应,优选在碱,例如Et3N的存在下以及在溶剂,如甲苯的存在下。HO-Cn-OH的例子原则上与上面关于第一优选制备方法所提到的一样。R1R2NH的例子是氨、苄基胺、二苄基胺、二异丙基胺、(R)-或(S)-1-甲基-苄基胺、哌啶、吗啉、(R,R)-或(S,S)-双-(1-甲基苄基)胺。
若本发明具有通式MLaXbSc的催化剂是阳离子性的,则反离子X是阴离子。适宜阴离子的例子是Cl、Br、I、OAc、BF4、PF6、ClO4、对甲苯磺酸、苯磺酸根、四(五氟苯基)硼酸根。非配位阴离子是优选的。若催化剂是阴离子性的,则X是阳离子。适宜阳离子的例子是碱金属,例如,锂、钠或钾,碱土金属如镁或钙,或者铵,或烷基取代的铵。
配体S可以是手性或非手性的。适宜配体S是烯烃,例如,马来酐或乙烯;二烯,例如1,5-环辛二烯、1,3-丁二烯和2,5-降冰片二烯;芳烃,例如苯、六甲基苯、甲基.异丙基苯和枯烯、η-5-配位的环戊二烯基配体,例如,环戊二烯基和五甲基环戊二烯基;二胺如1,2-二氨基乙烷。手性配体S的例子是(R,R)-1,2-环己烷二胺、(S,S)-1,2-二苯基-1,2-二氨基乙烷,(S,S)-1,2-二环己基-1,2-二氨基乙烷或(S)-1,1’-双(对甲氧基苯基)-1,2-丙二胺。
本发明还涉及通式I的手性配体的制备。另外,本发明还涉及由通式MLaXbSc代表的催化剂的应用,其中M是过渡金属,选自铑、铱和钌,X是反离子,S是配体,a介于0.5~3,b和c各自独立地介于0~2,其中L是通式(I)的手性配体
其中Cn连同2个O-原子和P-原子一起形成一个取代或未取代的带2~4个碳原子的环,R1和R2按上面的规定,所述应用为在在例如烯烃、酮、亚胺和肟衍生物的不对称氢化或不对称转移氢化中的应用。Cn和/或R1和/或R2是手性的或者是手性本体的一部分。与手性配体一起构成催化剂的合适的催化剂前体的例子有(COD=1,5-环辛二烯;nbd=降冰片二烯,L=本发明配体I,S=如上面规定的配体):[Rh(COD)Cl]2,[Rh(COD)2]BF4,[Rh(nbd)2]BF4,[Rh(nbd)2]ClO4,[Ir(COD)Cl]2,[Ir(COD)2]X(X=BF4,PF6,ClO4,SbF6,CF3SO3,B(C6F5)4),[Ru(COD)Cl2]n.
预形成络合物实例的例子是RhL2(CH3OH)2BF4、Rh(COD)L2BF4、RuL2(OAc)2、RuL2Br2、Ru(甲基烯丙基)2L2、Ru(η-6-苯)L2Br2、Ru(η-5-环戊二烯基)L2Cl、RuLSCl2、Ru(1,2-二苯基-1,2-二氨基乙烷)LCl2、IrL2(CH3OH)2PF6、Ir(COD)L2BF4。
在该催化剂的制备中,优选的是,金属与旋光活性配体的摩尔比选择在2∶1~1∶10之间,优选在1∶1~1∶6之间。优选的是,该催化剂就地制备,就是说在与实施不对称(转移)氢化反应的同一容器中制备,不经催化剂的中间离析。
适合不对称(转移)氢化反应的被作用物例如是前手性烯键不饱和化合物,就本发明目的而言,为简单计亦称烯烃,特别是亚烷基甘氨酸衍生物,例如,2-乙酰氨基-肉桂酸、2-苯甲酰氨基肉桂酸、2-乙酰氨基丙烯酸、N-乙酰-2-亚异丙基甘氨酸、N-乙酰-2-亚环己基甘氨酸、N-乙酰-3’-甲氧基-乙酰氧基-亚苄基甘氨酸,2-取代的马来酸,例如,2-苯基马来酸、2-甲基马来酸;亚烷基-琥珀酸衍生物,例如,衣康酸、2-亚苄基琥珀酸、2-亚异丁基-琥珀酸;1-取代的丙烯酸衍生物,例如,1-(6’-甲氧基-萘基)-丙烯酸、1-(4’-异丁基苯基)丙烯酸,1-取代的肉桂酸,例如,1-甲基-肉桂酸、1-(羟甲基)-肉桂酸和1-(氯甲基)-肉桂酸以及上述化合物的盐,例如,钠、锂、四烷基铵或三辛基铵盐,以及酯,例如二羧酸的甲酯、乙酯和叔丁酯,还有单酯,均可使用。
其他合适的被作用物是烯酰胺(enamides),例如,1-乙酰氨基苯乙烯、(Z)-2-乙酰-1-(对甲氧基亚苄基)-N-乙酰-1-(3’,4’-二甲氧基-亚苄基)-6,7-二甲氧基-1,2,3,4-四氢-异喹啉、1-苄氧羰基-4-叔丁氧羰基-2,3-脱氢-哌嗪-2-N-叔丁基酰胺,烯醇醚,例如,1-甲氧基-苯乙烯,烯醇酯,例如,5-亚甲基-丁内酯,烯丙基醇,例如,3,7-二甲基-2,7-辛二烯-1-醇(香叶醇),橙花醇、4-羟基-2-环戊烯酮。一项有关不对称烯烃氢化范围的最新综述,例如,由布朗(J.M.Brown)发表在《Comprehensive Asymmetric Catalysis》中,E.N.Jacobsen,A.Pfaltz和H.Yamamoto主编,Springer,柏林,1999,卷I,pp.121~182。
另一些合适的被作用物例如是前手性酮,具有通式(II):
其中R和R’彼此不相等且彼此独立地代表1~20个碳原子的烷基基团、芳基基团、芳烷基基团、链烯基基团或炔基基团,或者与它们键合的碳原子一起构成一个环,也有可能R和R’包含一个或多个杂原子或官能团,例如,乙酰苯、1-乙酰萘、2-乙酰萘、3-奎宁环酮、2-甲氧基环己酮、1-苯基-2-丁酮、苄基-异丙基甲酮、苄基丙酮、环己基甲基酮、叔丁基甲基酮、叔丁基苯基酮、异丙基苯基酮、乙基-(2-甲基乙基)-酮,邻-、间-或对-甲氧基乙酰苯,邻-、间-或对-(氟,氯)乙酰苯,邻-、间-或对-氰基乙酰苯,邻-、间-和/或对-三氟甲基乙酰苯,邻-、间-或对-硝基乙酰苯、2-乙酰芴、乙酰二茂铁、2-乙酰噻吩、3-乙酰噻吩、2-乙酰吡咯、3-乙酰吡咯、2-乙酰呋喃、3-乙酰呋喃、1-二氢茚酮、2-羟基-1-二氢茚酮、1-四氢萘酮、对甲氧基苯基-对’-氰基苯基二苯酮、环丙基-(4-甲氧基苯基)-甲酮、2-乙酰吡啶、3-乙酰吡啶、4-乙酰吡啶、乙酰吡嗪、α-卤代酮,例如,α-氯乙酰苯;α-氧代酸,例如,丙酮酸、苯基水合乙醛酸、4-苯基-2-氧代-丁酸、3-氧代,4,4-二甲基丁内酯及其酯和盐;β-氧代酸,例如,乙酰乙酸、4-苯基乙酰乙酸及其酯和盐;二酮,例如,联乙酰、联苯酰、乙酰丙酮;羟基酮,例如,羟基丙酮、苯偶姻和1-苯基-1-羟基丙酮。
可用于该不对称(转移)氢化反应的其他前手性化合物是通式(III)的前手性亚胺:
其中R、R’和R”,例如,彼此独立地代表1~20个碳原子的烷基基团、芳基基团、芳烷基基团、链烯基基团或炔基基团,或者与它们所键合的碳原子一起构成一个环,也有可能R、R’和R”包含一个或多个杂原子和官能团,且R”还可以是能够脱除的基团,例如,氧膦基、磺酰或苄基基团。亚胺的例子是由上面所描述的酮与烷基胺或芳基胺或氨基酸衍生物,例如,氨基酸酰胺、氨基酸酯、肽或多肽所制备的那些。合适的烷基胺或芳基胺的例子是苄基胺,例如,苄基胺或邻-、间-或对位取代的苄基胺、α-烷基苄基胺、萘基胺,例如,萘基胺、1,2,3,4,5,6,7或8-取代的萘基胺、1-(1-萘基)烷基胺或1-(2-萘基)烷基胺或二苯甲基胺。合适的亚胺的例子是N-(2-乙基-6-甲基苯基)-1-甲氧基-丙酮亚胺(acetonimine)、5,6-二氟-2-甲基-1,4-苯并嗪、2-氰基-1-吡咯啉、2-乙氧基羰基-1-吡咯啉、2-苯基-1-吡咯啉、2-苯基-3,4,5,6-四氢吡啶、3,4-二氢-6,7-二甲氧基-1-甲基-异喹啉、1-(对甲氧基苄基)-3,4,5,6,7,8-六氢异喹啉、N-二苯基氧膦基2-萘苯酮(naphtophenone)亚胺或N-甲苯磺酰-四氢萘酮亚胺。
可用于该不对称(转移)氢化反应的其他前手性化合物是通式(IV)的前手性肟及其衍生物:
其中R/R’按上面的规定,R例如,代表羟基基团、醚基团、酰氧基基团、磺酰氧基基团。合适的肟衍生物的例子是乙酰苯肟、N-乙酰氧基-对甲氧基乙酰苯亚胺和O-甲基-对氯乙酰苯肟。
本发明催化剂也适合用于从以下化合物(的对映异构体的外消旋混合物)出发制备旋光活性化合物:在分子中其他部位包含手性中心的烯烃、酮、亚胺或肟衍生物,其中优选两种对映异构体之一被氢化。
本发明催化剂的应用在一种或多种氢给体存在下实施,后者就本发明目的而言应理解为能够以某种方式将氢转移给被作用物的化合物。可用的适宜氢给体优选是H2,但也可以是1~10个碳原子的脂族或芳族醇,尤其是1~10个碳原子的仲醇,例如异丙醇或环己醇,或者5~10个碳原子的不饱和烃,例如,1,4-二氢苯或氢醌,还原性糖,例如,葡萄糖或甲酸衍生物,例如,甲酸铵或甲酸与三乙胺的共沸混合物。
被作用物与氢给体之间的摩尔比优选介于1∶1~1∶100。氢压可在宽范围内变化,且当要求快速反应或者尽可能低用量催化剂时,优选选择得尽可能高。氢压例如介于0.05~20MPa,优选0.1~10MPa,尤其是0.15~8MPa。
在不对称氢化中,过渡金属化合物中存在的金属与被作用物的摩尔比优选采用1∶10~1∶1,000,000,尤其是1∶50~1∶100,000之间的数值。
该催化剂可任选地以二聚体形式加入,其中该二聚体形式随后就地全部或部分地转变为单体形式。
不对称(转移)氢化实施的温度一般在反应速度与对映体选择性之间进行权衡,优选介于-20~120℃,尤其是0~60℃。不对称(转移)氢化优选在排除氧的条件下进行。优选的是,被作用物与溶剂不含任何氧、过氧化物或其他氧化性物质。
作为溶剂,可使用:醇、酯、酰胺、醚、酮、芳烃、卤代烃。优选采用乙酸乙酯、2-丙醇、丙酮、四氢呋喃(THF)、二氯甲烷、甲苯或二溴乙烷。不对称(转移)氢化也可在离子液体中进行,正如T.Welton在《化学评论》99,2071~2083(1999)中所描述的那样,以便简化产物的离析。必要的话,配体在离子液体中的溶解度可通过给配体提供诸如羧酸盐之类的极性基团予以提高。如果被作用物是液体,则氢化还可以非常适合地在没有溶剂的情况下进行。如果被作用物和/或产物几乎不溶于溶剂,则不对称(转移)氢化也可以淤浆形式进行。如果产物形成一种淤浆,其离析将大大简化。
优选的是,该(转移)氢化反应在不预先氢化的条件下实施。然而,也可在加入被作用物之前通过用氢气氢化或者以诸如NaBH4之类的还原剂处理使催化剂活化,以备不对称(转移)氢化。该(转移)氢化反应有时也利用在氢化之前或期间加入碱、酸、卤化物或N-羟基酰亚胺来加速。合适的碱是氮碱,例如,三乙胺、DBU和取代的或未取代的吡啶和无机碱,例如,KOtBu或Cs2CO3。合适的酸例如是HBr、三氟乙酸。合适的卤化物例如是碱金属卤化物或四烷基铵卤化物,例如LiI、LiBr、LiCl、NaI、四丁基碘化铵。合适的N-羟基-酰亚胺例如是N-羟基-邻苯二甲酰亚胺。
本发明将通过下面的例子加以说明,但是不受此限。
实施例
实例I
配体1的合成
在缓慢氮气流下,7mL(38mmol)六甲基磷三酰胺在40℃加入到10.0gS-(-)-1,1’-双-2-萘酚(34.9mmol)在50g无水甲苯中的悬浮体中。1min后,产物开始结晶。5h后,过滤分离出固体,以甲苯和戊烷洗涤并干燥。收率:11.0g(30.6mmol,88%),纯产物,根据TLC(薄层色谱法)(硅胶,EtOAc∶己烷=1∶1,31P-NMR和1H-NMR)。
实例II
配体2的合成
0.36g配体1(1.0mmol)、0.07g四唑(0.9mmol)和0.394mL二苄基胺(2.0mmol)在4mL无水甲苯中的悬浮体,在缓慢氮气流下沸腾-回流5h。然后,溶液冷却,并在硅胶薄层上过滤。以10%叔丁基甲基醚在己烷中的溶液洗涤该硅胶后,滤液彻底蒸发。收率:0.44g(0.87mmol,87%),纯,根据31P-NMR和1H-NMR和TLC。
实例III
配体3的合成
向PCl3(3.0mmol)、三乙胺(6.0mmol)和甲苯(5mL)的冷却溶液(-60℃)中,在5min内加入(S)-2,2-联萘酚(3.0mmol)和甲苯(25mL)的暖溶液(60℃)。搅拌2h后,反应混合物暖至室温,并在氩气氛下过滤。滤液以三乙胺(2.9mmol)和2.9mmol(R,R)-双(1-甲基苄基)-胺在-40℃处理。常温下16h后,混合物过滤,浓缩并以色谱术提纯。收率:41%,纯,根据31P-NMR和1H-NMR和TLC。
实例IV:烯烃的氢化
方法A.在0.1MPa并进行预氢化的条件下氢化
Rh(COD)2BF4(0.010mmol)和手性配体(0.022mmol)称重到10mLSchlenk容器中,加入磁性搅拌子,然后容器用橡胶隔膜封闭。3个真空/氮气周期,然后是2个真空/氢气周期。加入1.5mL溶剂并在0.1MPa氢气氛下搅拌1h。随后,加入被作用物(0.2mmol)在3.5mL溶剂中的溶液,反应混合物在氢气氛下搅拌。样品以4∶1乙酸乙酯∶己烷在硅胶上过滤,并蒸发。e.e.测定采用手性GC(气相色谱)或HPLC(高压液相色谱);转化率按1H-NMR。当反应结束后时,反应混合物按照与样品相同的方式处理并蒸发。结果载于表中。
方法B.在0.1MPa下的氢化实验(不进行预氢化)
Rh(COD)2BF4(0.010mmol)、手性配体(0.022mmol)和被作用物(0.2mmol)称重到配备橡胶隔膜盖和搅拌子的Schlenk管中,3个真空/氮气周期后,通过隔膜盖加入5mL新鲜蒸馏的溶剂,反应混合物在0.1MPa氢气氛下搅拌。样品和反应混合物如同在方法A中所述进行处理。结果载于表中。
方法C.0.5MPa下的氢化
Rh(COD)2BF4、手性配体(2.2当量,相对于Rh)和CH2Cl2(10mL)在氮气氛下加入到Schlenk容器中并搅拌。催化剂溶液利用针筒转移到50mL Buchi miniclave(微型反应釜)中。当CH2Cl2以外的溶剂应用到氢化中时,Rh(COD)2BF4和手性配体首先通过在氮气氛下、室温搅拌10min而溶解在CH2Cl2中。CH2Cl2在真空下蒸发,加入要求的溶剂(10mL),随后该催化剂溶液转移到Buchi微型反应釜中。
在许多情况中,该溶液在0.1MPa氢气氛下预氢化1h。被作用物(0.8mmol)溶解在10mL溶剂中的溶液,加入到Buchi微型反应釜中,并施加0.5MPa氢压。样品和反应混合物按如同方法A中所述进行处理。结果载于表中。
方法D.在6MPa下氢化
Rh(nbd)2BF4(4.0mg,0.0099mmol)和8.6mg手性配体1(0.022mmol)在氮气氛下溶解到配备橡胶隔膜盖和搅拌子的Schlenk管中的CH2Cl2(2.5mL,脱气的)中。该橙色溶液在室温搅拌5min,溶剂通过蒸发赶出。催化剂溶解在乙酸乙酯(20mL,脱气)中。α-乙酰氨基肉桂酸酯(240mg,1,09mmol)加入到125mL Parr压热釜中。3个氮气压力(0.29MPa)-解压周期后,加入乙酸乙酯(30mL)。橙色催化剂溶液(20mL)借助针筒加入到压热釜中,然后施加6.0MPa氢压。反应混合物利用具有螺旋桨叶的顶部搅拌器在680rpm下进行搅拌。4、10和20min后取样。4min后,反应已证明完成。生成N-乙酰-苯基丙氨酸甲酯的转化率大于99%,e.e.为97%。还可参见表2。
方法E.不同烯烃和烯酰胺在不同氢压下的氢化
Rh(COD)2BF4、手性配体(2.2当量,相对于Rh),被作用物和溶剂称重到压热釜中。压热釜封闭并通过3个氮压(0.29MPa)-解压周期达到惰性化。施加要求的氢压,反应混合物利用具有螺旋桨叶的顶部搅拌器以500rpm进行搅拌。反应进程利用氢的摄入来监测。结果载于表6中。
表1
L* | 配体构型 | 方法 | 温度℃ | 溶剂 | 时间(分钟) | 转化率(%) | 对映体过量(%) | 产物构型 |
1 | S | A | RT | MeOH | 1080 | 60 | 72 | R |
1 | R | A | RT | MeOH | 1320 | 98 | 75 | S |
1 | R | A | RT | CH2Cl2 | 240 | 100 | 947 | S |
1 | S | A | RT | CH2Cl2 | 240 | 100 | 95.5 | R |
1 | S | A | RT | EtOAc | 120 | >98 | 91.2 | R |
1 | S | A | 5 | CH2Cl2 | 180 | 96 | 97.2 | R |
1 | S | A | -10 | CH2Cl2 | 1080 | 86 | 98.0 | R |
1 | S | A | -10 | CH2Cl2 | 1080 | 92 | 97.9 | R |
1 | S | A | RT | ClCH2CH2Cl | 120 | >98 | 88.9 | R |
1 | S | A | RT | 丙酮 | 270 | 92 | 92.4 | R |
1 | S | A | RT | THF | 270 | 75 | 93.6 | R |
1 | S | B | RT | ClCH2CH2Cl | 300 | 100 | 96.0 | R |
1 | S | B | RT | CH2Cl2 | 120 | 94 | 97.0 | R |
1 | S | B | RT | EtOAc | 300 | >98 | 95.6 | R |
1 | S | A | RT | CH2Cl2+50mLH2O | 240 | 100 | 92.2 | R |
1 | S | B | 0 | CH2Cl2 | 1200 | 100 | 97.6 | R |
1 | S | B | 0 | EtOAc | 1200 | 85 | 98.4 | R |
1 | S | B | 0 | ClCH2CH2C | 1200 | 100 | 97.6 | R |
1 | S | B | -10 | CH2Cl2 | 1200 | 64 | 97.9 | R |
2 | S | A | RT | MeOH | 1260 | 16 | 56 | R |
3 | S,R,R | A | RT | CH2Cl2 | 240 | 100 | 42 | R |
6 | S | A | RT | MeOH | 11520 | 72 | 34 | R |
13 | R,R | A | RT | MeOH | 240 | 100 | 37 | R |
14 | R,R | A | RT | MeOH | 1440 | 100 | 77 | S |
表2 2-乙酰氨基-肉桂酸甲酯以配体1在高压下的氢化
(见实例IV)
方法 | 预氢化 | 温度(℃) | 溶剂 | Rh量(mol%) | 时间(分钟) | 转化率(%) | 对映体过量(%) |
C | 是 | RT | CH2Cl2 | 5 | 10 | >98 | 94.6 |
C | 是 | -5 | CH2Cl2 | 5 | 60 | >98 | 97.2 |
C | 是 | RT | CH2Cl2 | 0.5 | 40 | >98 | 94.7 |
C | 否 | RT | CH2Cl2 | 0.5 | 60 | 87 | 95.5 |
C | 否 | RT | 丙酮 | 0.5 | 60 | 94 | 95.5 |
C | 是 | RT | EtOAc | 0.5 | 60 | 58 | 95.7 |
C | 否 | RT | THF | 5 | 30 | >98 | 95.9 |
D | 否 | RT | EtOAc | 0.9 | 4 | >98 | 97 |
表4 各种烯烃采用本发明催化剂的氢化
(见实例IV,方法B,转化率>99%)
R3 | R4 | 温度(℃) | 溶剂 | 时间(分钟) | 对映体过量(%) |
H | Me | 0 | EtOAc | 1200 | >99 |
Ph | H | RT | EtOAc | 1200 | 80 |
H | Me | RT | CH2Cl2 | 240 | >99 |
H | Me | RT | EtOAc | 960 | >99 |
H | H | RT | EtOAc | 180 | 99 |
(p-OAc,m-OMe)-Ph | Me | RT | EtOAc | 1200 | 94 |
(p-OAc,m-OMe)-Ph | Me | RT | CH2Cl2 | 1200 | 95 |
(p-OAc,m-OMe)-Ph | Me | 0 | EtOAc | 1200 | 98 |
(p-OAc,m-OMe)-Ph | Me | 0 | CH2Cl2 | 1200 | 96 |
(p-F)-Ph | H | RT | EtOAc | 270 | 76 |
(p-F)-Ph | Me | RT | CH2Cl2 | 150 | 95 |
表5 衣康酸及衍生物采用本发明催化剂的氢化
(见实例IV,室温)
R5 | R6 | 方法 | 溶剂 | 时间(分钟) | 转化率(%) | 对映体过量(%) |
Me | Me | A | CH2Cl2 | 780 | >99 | 87 |
H | H | B | EtOAc | 1200 | >99 | 97 |
Me | Me | B | CH2Cl2 | 1200 | >99 | 94 |
H | H | B | CH2Cl2 | 1200 | >99 | 95 |
Me | Me | C,无预氢化0.5mol%Rh | CH2Cl2 | 60 | 75 | 91 |
表6 烯酰胺采用本发明催化剂的氢化
(见实例IV,在CH2Cl2,室温,转化率>99%)
R7 | 配体 | 方法 | Rh量(mol%) | 氢压(MPa) | 时间(分钟) | 对映体过量(%) |
H | 1 | B | 5 | 0.5 | 1200 | 92 |
p-Cl | 2 | E | 2 | 1.5 | 210 | 58 |
p-Cl | 20,R1和R2=Me | E | 2 | 1.5 | 210 | 89 |
p-Cl | 22,R1和R2=Me | E | 2 | 1.5 | 210 | 86 |
p-Cl | 1 | E | 2 | 1.5 | 210 | 93 |
p-Ome | 1 | E | 2 | 1.5 | 240 | 84 |
p-Ome | 22,R1和R2=Me | E | 2 | 1.5 | 240 | 62 |
p-Ome | 20,R1和R2=Me | E | 2 | 1.5 | 240 | 83 |
p-Ome | 2 | E | 2 | 1.5 | 240 | 53 |
对比实验
手性二齿配体的氢化(不构成本发明的一部分)。按照方法A(参见实例IV)的2-乙酰氨基肉桂酸甲酯,除非另行指出一律采用1.1当量手性配体的氢化)。结果载于表3中。该结果表明,二齿磷酰胺配体通常将导致反应缓慢和对映体选择性低下。
表3
L* | 配体构型 | 注 | 溶剂 | 时间(分钟) | 转化率(%) | 对映体过量(%) | 产物构型 |
28 | S,S | MeOH | 1140 | 100 | 22 | R | |
28 | S,S | CH2Cl2 | 1140 | 100 | 42 | R | |
29 | R,R | MeOH | 1380 | 6 | 52 | R | |
29 | R,R | 2.2eq.配体 | MeOH | 1320 | - | - | - |
29 | R,R | CH2Cl2 | 1440 | 56 | 72 | R | |
30 | S,S | MeOH | 1380 | - | - | - | |
30 | S,S | 2.2eq.配体 | MeOH | 1320 | - | - | - |
30 | S,S | CH2Cl2 | 1440 | 100 | 25 | S | |
31 | R,S,R,S | MeOH | 1260 | 18 | 12 | S | |
31 | R,S,R,S | CH2Cl2 | 1440 | 7 | 28 | R | |
32 | S,S,S,S | MeOH | 1260 | 40 | 6 | R | |
32 | S,S,S,S | CH2Cl2 | 1440 | 100 | 80 | S | |
33 | R,R,R,R | MeOH | 1320 | 100 | 14 | S | |
34 | R,R,R,R | MeOH | 1320 | 40 | 15 | S |
二齿配体,不形成本发明的一部分
实例V:乙酰苯的氢化
催化剂络合物Ru(配体)(二胺)Cl2的合成
[RuCl2(对甲基.异丙基苯)]2(9mg)和2当量配体1(21.9mg)加入到氮气氛下的Schlenk烧瓶中。加入DMF(1.0mL),混合物通过3个真空/N2周期达到脱气。然后,它在65℃搅拌16~24h(或3h,90℃)。生成一种RuCl2(配体)2(dmf)n络合物。然后,将它冷却至室温,再加入1当量(S,S)-1,2-二苯基-1,2-二氨基乙烷(DPEN)(6.3mg)。混合物再搅拌16~24h后,将它用于氢化。
光谱数据:RuCl2(配体)2(dmf)nP-NMR:148.8ppm;
Ru(配体)(DPEN)Cl2P-NMR:147.7(游离配体)和172.2(络合物)ppm。
预制的通式Ru(L)Cl2[(S,S)-1,2-二苯基乙二胺](0.1mmol)络合物和被作用物(10mmol)称重到压热釜中。在缓慢氮气流下加入脱气的MeOH(50mL)和K2CO3(2.0mmol),封闭压热釜并通过3个氮压(0.29MPa)-解压周期将其惰性化。施加要求的氢压(5.0MPa)和温度(50℃),反应混合物借助带螺旋桨叶的顶部搅拌器以5O0rpm搅拌。
结果:
L=配体1∶45min后,93%转化率;e.e.为58%。
L=配体1,但其中N-甲基基团换成了异丙基基团:150min后,98%转化率;e.e.,67%。
实例VI采用配体1的钌(II)和铱(I)络合物的不对称转移氢化
利用铱(I)催化剂的乙酰苯不对称还原
[IrCl(COD)]2(0.01mmol,0.25mol%,6.7mg)和(S)-1配体(0.04mmol,1mol%,14.4mg)的混合物在干燥、脱气的异丙醇(5mL)中,在80℃氮气下加热1h。冷却至室温后,催化剂溶液加入到叔丁醇钾(0.125mmol,3.125mol%,14.0mg)和乙酰苯(4mmol,471μl)在干燥、脱气的异丙醇(35mL)中的溶液中。反应在室温、氮气下搅拌表中所载时间并利用GC分析监测。结果载于表7中。
采用钌(II)催化剂的乙酰苯不对称还原
[RuCl2(对甲基.异丙基苯)]2(0.0125mmol,0.25mol%,7.7mg)和(S)-Monophos配体(0.05mmol,1mol%,18.0mg)在干燥、脱气的异丙醇(5mL)中的混合物,在80℃、氮气下加热1h。冷却至室温后,催化剂溶液加入到叔丁醇钾(0.15mmol,3mol%,16.8mg)和乙酰苯(5mmol,588μl)在干燥、脱气的异丙醇(40mL)中的溶液中。反应在室温氮气下搅拌表中所载时间并利用GC分析监测。
结果载于表7中。
表7钌和铱络合物催化的乙酰苯以异丙醇进行不对称转移氢化
金属前体 | 时间(h) | 转化率(%) | 对映体过量(主要对映体) |
[IrCl(cod)]2 | 1.5 | 8 | 25(R) |
21 | 51 | 27(R) | |
[RuCl2(对甲基异丙基苯)]2 | 1 | 17 | 47(R) |
21 | 24 | 46(R) |
Claims (18)
2.权利要求1的催化剂,其中Cn代表主要为一种构型的手性取代的C4链。
3.权利要求2的催化剂,其中Cn连同两个O原子和P原子构成4个碳原子的7元环,其中碳原子两个一组地构成芳基基团或萘基基团的一部分。
4.权利要求1~3中任何一项的催化剂,其中R1和R2各自独立地代表烷基基团。
5.权利要求4的催化剂,其中R1和R2都代表甲基基团。
6.制备通式1的配体的方法,其中具有通式HO-Cn-OH-其中n按上面规定-的二醇与P(N(R3)2)3-其中R3是甲基或乙基-起反应,随后与R1R2NH反应,其中R1和R2各自独立地代表任选取代的烷基、芳基、烷芳基或芳烷基基团或者可与它们所键合的N原子一起形成一个杂环的环。
7.制备通式1的配体的方法,其中具有通式HO-Cn-OH-其中n按上面规定-的二醇与PCl3起反应,随后与R1R2NH反应,其中R1和R2各自独立地代表任选取代的烷基、芳基、烷芳基或芳烷基基团或者可与它们所键合的N原子一起形成一个杂环的环。
9.权利要求8的方法,其中烯键不饱和化合物、酮或亚胺发生不对称氢化或不对称转移氢化反应。
10.权利要求9的方法,其中Cn代表主要为一种构型的手性取代的C4链。
11.权利要求10的方法,其中Cn连同2个O原子和P原子一起构成一个具有4个碳原子的环,碳原子两个一组地构成芳基基团或萘基基团的一部分。
12.权利要求8~11中任何一项的方法,其中不对称氢化或不对称转移氢化是在一种非质子溶剂存在下进行的。
13.权利要求8~11中任何一项的方法,其中不对称氢化或不对称转移氢化是在一种离子液体存在下进行的。
14.权利要求8~13中任何一项的方法,其中氢给体选自氢气、异丙醇和甲酸与三乙胺的混合物。
15.权利要求8~14中任何一项的方法,其中不对称氢化或不对称转移氢化是在0.1~10MPa压力下进行的。
16.权利要求8~15中任何一项的方法,其中采用一种在分子中其他部位包含手性中心的烯烃、酮或亚胺。
17.权利要求8~16中任何一项的方法,其中催化剂是就地制备的。
18.权利要求8~17中任何一项的方法,其中被作用物和/或产物与溶剂一起形成淤浆。
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WO2004024684A2 (en) * | 2002-09-13 | 2004-03-25 | Yale University | Enantioselective amination and etherification |
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CN1309728C (zh) * | 2004-07-30 | 2007-04-11 | 中国科学院上海有机化学研究所 | 一类手性有机-无机高分子组装体催化剂、合成方法及用途 |
CN100482671C (zh) * | 2004-09-29 | 2009-04-29 | 中国科学院上海有机化学研究所 | 手性单磷配体、合成方法及其用途 |
US8383872B2 (en) * | 2004-11-16 | 2013-02-26 | Velocys, Inc. | Multiphase reaction process using microchannel technology |
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