CN106518931B - 一种新型螺环膦-羧酸的铱络合物及其制备方法和应用 - Google Patents
一种新型螺环膦-羧酸的铱络合物及其制备方法和应用 Download PDFInfo
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- CN106518931B CN106518931B CN201610922754.1A CN201610922754A CN106518931B CN 106518931 B CN106518931 B CN 106518931B CN 201610922754 A CN201610922754 A CN 201610922754A CN 106518931 B CN106518931 B CN 106518931B
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- carboxylic acid
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- alkyl
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- 229910052741 iridium Inorganic materials 0.000 title claims abstract description 36
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 125000003003 spiro group Chemical group 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000003446 ligand Substances 0.000 claims abstract description 16
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims abstract description 13
- 150000001735 carboxylic acids Chemical class 0.000 claims abstract description 13
- -1 sec-hexyl Chemical group 0.000 claims description 130
- 238000006243 chemical reaction Methods 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 239000003054 catalyst Substances 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 18
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000002503 iridium Chemical class 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 claims description 2
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 2
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 2
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 2
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229940043279 diisopropylamine Drugs 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 150000002504 iridium compounds Chemical class 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005932 isopentyloxycarbonyl group Chemical group 0.000 claims description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical group CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005933 neopentyloxycarbonyl group Chemical group 0.000 claims description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 claims description 2
- 125000002872 norbornadienyl group Chemical group C12=C(C=C(CC1)C2)* 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000006608 n-octyloxy group Chemical group 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 150000002500 ions Chemical class 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- DURJBIVOBGHCHY-UHFFFAOYSA-N 3-Methyleneheptanoic acid Chemical compound CCCCC(=C)CC(O)=O DURJBIVOBGHCHY-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000002390 rotary evaporation Methods 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 238000004296 chiral HPLC Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 239000002274 desiccant Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000000605 extraction Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000004679 31P NMR spectroscopy Methods 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000011914 asymmetric synthesis Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical group C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 150000007934 α,β-unsaturated carboxylic acids Chemical class 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005356 chiral GC Methods 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
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Classifications
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- 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
- C07F15/0033—Iridium 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
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/249—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
-
- 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
- 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
- B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
-
- 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
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Abstract
本发明涉及一种螺环膦‑羧酸的铱络合物及其制备方法和应用。具有式(I)所示结构的化合物,其中n=0~3;R1、R2、R3、R4、R5、R6、R7的取值如权利要求1所定义。以取代的7‑羧基‑7′‑二芳基膦基‑1,1′‑螺双二氢茚为配体,在碱的作用下形成羧酸负离子,再与铱前体进行络合,可以得到不同的铱/螺环膦‑羧酸络合物。本发明螺环膦‑羧酸的铱络合物能够催化多种不饱和羧酸的不对称氢化反应,表现出很高的活性和对映选择性,具有很好的工业化前景。
Description
技术领域
本发明涉及一种新型螺环膦-羧酸的铱络合物及其制备方法和应用。具体地讲是以取代的7-羧基-7′-二芳基膦基-1,1′-螺双二氢茚为配体,在碱的作用下形成羧酸负离子,再与铱前体进行络合,可以得到不同的铱/螺环膦-羧酸络合物。该新型螺环膦-羧酸的铱络合物能够催化多种不饱和羧酸的不对称氢化反应,表现出很高的活性和对映选择性,具有很好的工业化前景。
背景技术
过渡金属催化的不对称合成是当前有机合成化学研究领域中的热点(Ohkuma,T.;Kitamura,M.;Noyori,R.Catalytic Asymmetric Synthesis,Wiley,New York,2000)。催化不对称合成的关键是手性催化剂的合成,设计合成新型手性催化剂是催化不对称合成发展的原动力。
在过去的几十年里,人们发展了一系列膦配体和氮配体的Ru、Rh、Ir络合物来实现许多不饱和化合物的不对称氢化(1.Tang,W.;Zhang,X.Chem.Rev.2003,103,3029;2.He,Y.-M.;Fan,Q.-H.Org.Biomol.Chem.2010,8,2497;3.Zhao,B.;Han,Z.;Ding,K.Angew.Chem.Int.Ed.2013,52,4744)。但是以氧原子作为配位基团的手性配体很少被成功应用于不对称催化氢化反应中。最近,Reek和Pfaltz等人分别发展了两类以氧作为配位基团的膦-酰胺配体,并将其应用于Rh和Ir催化的官能团化烯烃的不对称氢化反应中,获得中等或较高的对映选择性(1.Meeuwissen,J.;Detz,R.J.;Sandee,A.J.;de Bruin,B.;Reek,J.N.H.Dolton Trans.2010,39,1929;2.Rageot,D.;Woodmansee,D.H.;Pugin,B.;Pfaltz,A.Angew.Chem.Int.Ed.2011,50,9598)。但是上述两种膦-氧配体的过渡金属络合物稳定性都不高,很容易分解,也不能用硅胶柱层析的方法提纯。尽管羧酸作为导向基已经被广泛的应用到C-H键活化反应中(1.Engle,K.M.;Mei,T.-S.;Wasa,M.;Yu,J.-Q.Acc.Chem.Res.2012,45,788;2.Shi,G.;Zhang,Y.Adv.Synth.Catal.2014,356,1419),但是在不对称催化氢化领域,含有羧酸配位点的手性催化剂却从未被使用过。本专利发展了一类具有螺双二氢茚骨架的手性离子型膦-羧酸配体的铱络合物,公开了这类膦-羧酸配体的铱络合物的制备及其在不饱和羧酸的不对称催化氢化中的应用。该手性膦-羧酸配体的铱络合物催化剂具有以下优点:1)能够实现多种不饱和羧酸的不对称催化氢化,特别是在β-烷基取代-β,γ-不饱和羧酸的氢化反应中给出迄今最高的对映选择性;2)结构简单,无需添加BArF-阴离子来稳定催化剂;3)催化剂有较高的稳定性,可以通过柱层析提纯,并且对空气稳定。
发明内容
本发明的目的是提供一种新型螺环膦-羧酸的铱络合物及其制备方法和应用,可以克服已有技术的缺点。该新型螺环膦-羧酸的铱络合物能够催化多种不饱和羧酸的不对称氢化反应,表现出很高的活性和对映选择性,具有很好的工业化前景。
本发明提供的螺环膦-羧酸的铱络合物具有式(I)所示结构的化合物:
其中:是环辛二烯;n=0~3;R1、R2分别为H、C1~C8烷基、卤代烷基、C1~C8烷氧基、C2~C8酰氧基、C1~C8酰基、C2~C8酯基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、卤素、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基,或当n≥2时为并脂环或并芳环;R1和R2可以相同,也可以不同;
R3、R4、R5、R6分别为H、C1~C8烷基、卤代烷基、C1~C8烷氧基、C2~C8酰氧基、C1~C8酰基、C2~C8酯基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、卤素、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基,或R3~R4、R5~R6为并脂环或芳环;R3、R4、R5、R6可以相同,也可以不同;
R7为C1~C8烷基、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基;
所述取代的苯基或萘基中,取代基为C1~C8烷基、C1~C8烷氧基、羟基、C2~C8酰氧基、卤素、氨基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、C1~C8酰基、C2~C8酯基中的一种或几种;取代基数目为0~5;
环辛二烯配体可以被乙烯、降冰片二烯取代。
本发明所述的螺环膦-羧酸的铱络合物(I)中:
所述的C1~C8烷基为甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、仲戊基、叔戊基、正己基、异己基、新己基、仲己基、叔己基、正庚基、异庚基、新庚基、仲庚基、叔庚基、正辛基、异辛基、新辛基、仲辛基或叔辛基;
所述的C1~C8烷氧基为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、异戊氧基、新戊氧基、仲戊氧基、叔戊氧基、正己氧基、异己氧基、新己氧基、仲己氧基、叔己氧基、正庚氧基、异庚氧基、新庚氧基、仲庚氧基、叔庚氧基、正辛氧基、异辛氧基、新辛氧基、仲辛氧基或叔辛氧基;
所述的C1~C8酰基为甲酰基、乙酰基、丙酰基、正丁酰基、异丁酰基、正戊酰基、异戊酰基、仲戊酰基、新戊酰基、正己酰基、异己酰基、新己酰基、仲己酰基、正庚酰基、异庚酰基、新庚酰基、仲庚酰基、正辛酰基、异辛酰基、新辛酰基、仲辛酰基、1-环丙基甲酰基、1-环丁基甲酰基、1-环戊基甲酰基、1-环己基甲酰基、1-环庚基甲酰基;
所述的C2~C8酰氧基为乙酰氧基、丙酰氧基、正丁酰氧基、异丁酰氧基、正戊酰氧基、异戊酰氧基、仲戊酰氧基、新戊酰氧基、正己酰氧基、异己酰氧基、新己酰氧基、仲己酰氧基、正庚酰氧基、异庚酰氧基、新庚酰氧基、仲庚酰氧基、正辛酰氧基、异辛酰氧基、新辛酰氧基、仲辛酰氧基、1-环丙基甲酰氧基、1-环丁基甲酰氧基、1-环戊基甲酰氧基、1-环己基甲酰氧基、1-环庚基甲酰氧基;
所述的C2~C8酯基为甲氧羰基、乙氧羰基、丙氧羰基、异丙氧羰基、丁氧羰基、异丁氧羰基、正戊氧羰基、异戊氧羰基、新戊氧羰基、仲戊氧羰基、叔戊氧羰基、环戊氧羰基、正己氧羰基、异己氧羰基、新己氧羰基、仲己氧羰基、叔己氧羰基、环己氧羰基、正庚氧羰基、异庚氧羰基、新庚氧羰基、仲庚氧羰基、叔庚氧羰基、环庚氧羰基;
所述的卤代烷基为含氟、氯、溴或碘的卤代烷基。
本发明所述的螺环膦-羧酸的铱络合物(I)还包含具有相同的化学结构通式但具有不同的立体结构和旋光性能的外消旋体、右旋体和左旋体。
所述的螺环膦-羧酸的铱络合物的制备方法是经过如下步骤制备:在有机溶剂(二氯甲烷、三氯甲烷或1,2-二氯乙烷中的一种或几种)中,10~50℃下,螺环膦-羧酸(1mol)、一价铱化合物,如[Ir(COD)Cl]2(COD=环辛二烯)(0.5~1mol)、碱,如Na2CO3(0.5mol),反应0.5~24小时,制备得到不同取代基的螺环膦-羧酸的铱络合物:
其中:n=0~3;R1、R2、R3、R4、R5、R6、R7的取值如上述化合物(I)所定义;COD为1,5-环辛二烯;环辛二烯配体可以被乙烯、降冰片二烯取代。
所述的螺环膦-羧酸的铱络合物的应用是用于催化不饱和羧酸的不对称氢化反应。
其中:[Ir]为螺环膦-羧酸的铱络合物(I);R8、R9、R10是C1~C8烷基、卤代烷基、苄基、苯乙基、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基、C1~C8烷氧基、苯甲氧基、苯氧基;星号标记的位置为手性中心。
具体过程是:将催化剂和底物加入反应釜内管中,加入添加剂和溶剂,密封反应釜并用氢气置换3~10次,充氢气至指定压力,在指定温度下搅拌反应至结束;
所述的催化氢化反应条件是:所用溶剂是C1~C6的醇类;催化剂用量为0.001~1mol%;底物浓度为0.001~10.0M;添加剂为异丙胺、叔丁胺、二甲胺、二乙胺、二异丙胺、二异丙基乙基胺、三甲胺、三乙胺、1,8-二氮杂双环[5,4,0]十一-7-烯、1,4-二氮杂二环[2,2,2]辛烷、氢化钠、氢氧化钠、碳酸钠、碳酸氢钠、叔丁醇钠、氢氧化钾、碳酸钾、碳酸氢钾、叔丁醇钾、氢氧化铯、碳酸铯中的一种或几种;反应温度为0~100℃;氢气压力为0.1~10MPa;反应10分钟~48小时。
本发明以螺环膦-羧酸作为起始原料,在碱的作用下和铱前体进行络合得到含取代基的铱/螺环膦-羧酸络合物。该新型螺环膦-羧酸的铱络合物能够催化多种不饱和羧酸的不对称氢化反应,并表现出以下特点:工作压力较低(通常为0.3MPa),即使在常压下也能很好地完成不对称催化氢化;底物适用范围很广,对一系列不饱和羧酸都能给出很好的结果;对官能团的耐受性很好;对映选择性可达97%ee。上述特点表明,本发明所提供的新型螺环膦-羧酸的铱络合物催化剂克服了已有技术的缺点,是不对称催化氢化的最高效的配体和催化剂之一,特别对β-烷基取代-β,γ-不饱和羧酸的不对称催化氢化给出目前最好的结果,具有很好的工业化前景。
附图说明:
图1为(S)-2d的单晶结构
具体实施方式
通过下述实施实例将有助于近一步理解本发明,但不应将此理解为本发明上述主题的保护范围仅限于以下的实施例,凡基于本发明上述内容所实现的技术均属于本发明的范围。
特别说明:
实施例中使用了缩写,其含义如下:
Me是甲基,Et是乙基,nPr是正丙基,iPr是异丙基,nBu是正丁基,tBu是叔丁基,n-Pent是正戊基,n-Hept是正庚基,Ph是苯基,Bn是苄基,An是对甲氧基苯基,Xyl是3,5-二甲基苯基,DTB是3,5-二叔丁基苯基;NMR是核磁共振,手性HPLC是装有手性色谱柱的高效液相色谱,手性GC是装有手性毛细管柱的气相色谱;ee值为对映异构体过量值;S/C是底物与催化剂物质的量的比。
所用溶剂在使用前用通用的标准操作提纯,干燥;所用试剂均为市售或按照已有文献方法合成得到,并在使用前提纯。
实施例1:螺环膦-羧酸的铱络合物的制备
在手套箱中,将(S)-1a(168mg,0.25mmol)、[Ir(COD)Cl]2(84mg,0.125mmol)和Na2CO3(13mg,0.125mmol)称入一10mL Schlenk瓶中,取出后加入二氯甲烷(2mL),水浴控温40℃反应30分钟,TLC确定配体络合完全。反应结束,冷至室温,浓缩后的残余物经硅胶柱层析(石油醚/乙酸乙酯=1∶1,v/v)得桔红色泡沫状固体202mg,收率:83%。熔点:212~213℃,[α]D 25+200(c 0.5,二氯甲烷),1H NMR(400MHz,CDCl3)δ8.17(d,J=6.8Hz,1H),7.98(s,1H),7.62(t,J=8.4Hz,1H),7.43(s,1H),7.38(s,1H),7.34-7.26(m,3H),7.15(t,J=7.2Hz,1H),6.92(s,1H),6.38(s,1H),6.05(s,1H),4.37(t,J=6.4Hz,1H),3.53(d,J=7.2Hz,1H),3.34(s,1H),2.94-2.74(m,5H),2.43-2.32(m,2H),2.09(dd,J=15.8and9.3Hz,1H),1.90(dd,J=9.9and 4.9Hz,1H),1.54-0.81(m,41H),0.73(d,J=10.8Hz,1H),0.53-0.37(m,2H);31P NMR(161MHz,CDCl3)δ11.1(s);13C NMR(101MHz,CDCl3)δ174.7,149.7,149.6,146.1,146.0,142.5,140.6,135.9,135.4,132.5,131.6,130.6,130.2,127.7,127.4,127.1,126.7,126.6,125.6,125.4,124.7,121.9,120.1,73.0,64.1,63.8,63.3,63.0,60.3,39.7,34.9,34.8,33.8,31.3,31.2,30.8,30.5,30.1,27.4,27.3.HRMS(ESI)Calcd for[C54H68IrNaO2P,M+Na]+:995.4478,Found:995.4480.
以下化合物的合成方法与实施例1相同。
收率:75%。桔红色泡沫状固体,熔点:205~206℃,[α]D 25+318(c 0.5,二氯甲烷),1H NMR(400MHz,CDCl3)δ8.24(d,J=6.0Hz,1H),7.48(t,J=8.0Hz,1H),7.37-7.32(m,3H),7.27-7.23(m,2H),7.11(t,J=8.0Hz,2H),7.04(s,2H),5.73(s,1H),4.40(td,J=7.6and2.2Hz,1H),3.57-3.52(m,1H),3.20(t,J=7.2Hz,1H),2.92-2.67(m,5H),2.46-2.38(m,2H),2.31(s,6H),2.22(s,6H),2.09(dd,J=16.0and 9.2Hz,1H),1.95-1.88(m,1H),1.58-1.42(m,3H),1.23-1.15(m,1H),1.05-0.96(m,1H),0.79-0.73(m,1H),0.60-0.50(m,1H),0.12(dd,J=22.1and 10.1Hz,1H);31P NMR(161MHz,CDCl3)δ9.9(s);13C NMR(101MHz,CDCl3)δ174.5,149.9,149.8,146.2,146.1,143.2,140.5,138.3,137.0,136.9,135.6,135.2,133.4,132.7,132.42,132.38,132.04,132.02,130.4,129.7,129.3,127.9,127.6,127.1,127.0,125.8,125.2,118.6,73.7,64.1,63.9,63.8,63.0,61.1,39.6,34.83,34.77,34.1,31.1,30.8,30.6,30.3,27.4,27.3,21.5,21.4.HRMS(ESI)Calcd for[C42H44IrNaO2P,M+Na]+:827.2600,Found:827.2603.
收率:78%。桔红色泡沫状固体,熔点:195~196℃,[α]D 25+273(c 0.5,二氯甲烷),1H NMR(400MHz,CDCl3)δ8.19(dd,J=5.5and 2.3Hz,1H),7.57(t,J=10.4Hz,2H),7.39-7.33(m,3H),7.25-7.23(m,1H),7.13-7.06(m,2H),6.93(d,J=10.0Hz,2H),6.81(d,J=10.4Hz,2H),6.59(s,1H),4.45(dd,J=7.3and 5.5Hz,1H),3.86(s,3H),3.81(s,3H),3.57-3.52(m,1H),3.23-3.20(m,1H),2.92-2.73(m,5H),2.40-2.18(m,3H),1.95-1.87(m,1H),1.60-1.21(m,4H),1.07-1.01(m,1H),0.87-0.66(m,2H),0.25(dd,J=22.2and 10.3Hz,1H);31P NMR(161MHz,CDCl3)δ6.4(s);13C NMR(101MHz,CDCl3)δ174.5,161.7,160.2,149.8,149.7,146.2,146.1,143.0,140.6,137.2,134.3,132.1,132.0,131.9,129.6,128.7,128.3,127.4,127.1,127.0,126.9,125.9,125.6,121.3,120.9,119.2,114.5,113.2,113.1,74.4,64.3,64.0,63.6,63.0,60.8,55.5,55.4,39.8,34.8,34.7,34.2,31.3,31.1,30.6,30.5,27.1,27.0.HRMS(ESI)Calcd for[C40H40IrNaO4P,M+Na]+:831.2186,Found:831.2182.
收率:80%。桔红色泡沫状固体,熔点:190~191℃,[α]D 25+277(c 0.5,二氯甲烷),1H NMR(400MHz,CDCl3)δ8.20(d,J=5.2Hz,1H),7.64(s,2H),7.48-7.24(m,10H),7.12(t,J=7.6Hz,1H),6.69(s,2H),4.41(s,1H),3.55(d,J=6.0Hz,1H),3.26(s,1H),2.92-2.75(m,5H),2.43-2.31(m,2H),2.19(dd,J=15.7and 9.3Hz,1H),1.91(d,J=2.4Hz,1H),1.55-1.46(m,3H),1.15-1.14(m,1H),0.97-0.96(m,1H),0.78-0.76(m,1H),0.62-0.60(m,1H),0.12-0.09(m,1H);31P NMR(161MHz,CDCl3)δ8.9(s);13C NMR(101MHz,CDCl3)δ174.5,150.0,149.9,146.4,146.3,142.9,140.5,136.2,135.7,132.33,132.30,131.7,131.1,130.6,130.3,129.0,128.9,127.7,127.6,127.4,127.3,127.2,127.1,126.0,125.6,119.1,74.4,64.5,64.2,64.1,63.0,61.0,39.7,35.034.9,34.2,31.1,31.0,30.6,30.4,27.1,27.0.HRMS(ESI)Calcd for[C38H36IrNaO2P,M+Na]+:771.1974,Found:771.1977.
实施例2:(S)-2d的单晶测定参数
表1 (S)-2d的单晶测定参数
实施例3:不同铱催化剂用于3-丁基-3-丁烯酸的不对称氢化
在手套箱中称取催化剂(0.005mmol)和3-丁基-3-丁烯酸3a(71mg,0.5mmol)于装有搅拌子的反应内管中,密封备用。取出后加入碳酸铯(82mg,0.25mmol)和甲醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,45℃搅拌反应至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物(R)-4a。{[α]D 25+4.70(c0.40,二氯甲烷),1H NMR(400MHz,CDCl3)δ2.35(dd,J=15.2and 6.0Hz,1H),2.14(dd,J=14.8and 8.0Hz,1H),1.99-1.89(m,1H),1.37-1.17(m,6H),0.96(d,J=6.8Hz,3H),0.89(t,J=6.8Hz,3H).}。1H NMR分析其转化率,将其转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表2:
表2:不同铱催化剂用于3-丁基-3丁烯酸3a的不对称氢化的实验结果
实施例4:在不同添加剂时3-丁基-3-丁烯酸的不对称氢化
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)和3-丁基-3-丁烯酸3a(71mg,0.5mmol)于装有搅拌子的反应内管中,密封备用。取出后加入不同添加剂和甲醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,45℃下搅拌反应至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物(R)-5a。1H NMR分析其转化率,将其转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表3:
表3:不同添加剂时3-丁基-3-丁烯酸3a不对称催化氢化的实验结果
实施例5:在不同温度下3-丁基-3-丁烯酸的不对称氢化
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)和3-丁基-3-丁烯酸3a(71mg,0.5mmol)于装有搅拌子的反应内管中,密封备用。取出后加入碳酸铯(82mg,0.25mmol)和甲醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,在不同温度下搅拌反应至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物)R)-4a。1H NMR分析其转化率,将其转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表4:
表4:不同温度下3-丁基-3-丁烯酸3a不对称催化氢化的实验结果
实施例6:在不同压力下3-丁基-3-丁烯酸的不对称氢化
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)和3-丁基-3-丁烯酸3a(71mg,0.5mmol)于装有搅拌子的反应内管中,密封备用。取出后加入碳酸铯(82mg,0.25mmol)和甲醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定相应氢气压力,65℃下搅拌反应至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物(R)-4a。1HNMR分析其转化率,将其转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表5:
表5:不同压力下3-丁基-3-丁烯酸3a不对称催化氢化的实验结果
实施例7:在不同溶剂中3-丁基-3-丁烯酸的不对称氢化
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)和3-丁基-3-丁烯酸3a(71mg,0.5mmol)于装有搅拌子的反应内管中,密封备用。取出后加入碳酸铯(82mg,0.25mmol)和溶剂(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,在65℃下搅拌反应至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物(R)-4a。1H NMR分析其转化率,将其转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表6:
表6:不同溶剂中3-丁基-3-丁烯酸3a不对称催化氢化的实验结果
实施例8:氢化β-烷基取代-β,γ-不饱和羧酸
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)、β-烷基取代-β,γ-不饱和羧酸3(0.5mmol)、碳酸铯(82mg,0.25mmol)于装有搅拌子的反应内管中,密封备用。取出后用注射器加入正丁醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,65℃搅拌至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物4,1H NMR分析其转化率,所有反应均完全转化。将产物转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表7。
表7:β-烷基取代-β,γ-不饱和羧酸的不对称催化氢化结果
实施例9:氢化α,β-不饱和羧酸
在手套箱中称取催化剂(S)-2d(3.7mg,0.005mmol)、α,β-不饱和羧酸5(0.5mmol)、碳酸铯(82mg,0.25mmol)于装有搅拌子的反应内管中,密封备用。取出后用注射器加入正丁醇(2mL),将内管放置于氢化反应釜中,通过加压-放气的操作(3-5次)置换为氢气氛围,最后设定氢气压力为0.3MPa,65℃搅拌至压力停止下降。而后停止搅拌,放出氢气,将反应体系旋蒸浓缩后,以3N盐酸水溶液调节体系pH<3,用乙醚(10mL×3)萃取,合并有机相,用饱和食盐水洗涤,无水硫酸钠干燥。抽滤除去干燥剂,旋蒸脱溶,得到目标产物6,1H NMR分析其转化率,所有反应均完全转化。将产物转化为相应酰胺后手性HPLC分析其ee值。所得实验结果见表8。
表8:其他类型不饱和羧酸的不对称催化氢化结果
Claims (9)
1.一种螺环膦-羧酸的铱络合物,其特征在于它具有式(I)所示结构:
其中:是环辛二烯;n=0~3;R1、R2分别为H、C1~C8烷基、卤代烷基、C1~C8烷氧基、C2~C8酰氧基、C1~C8酰基、C2~C8酯基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、卤素、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基;R1和R2可以相同,也可以不同;
R3、R4、R5、R6分别为H、C1~C8烷基、卤代烷基、C1~C8烷氧基、C2~C8酰氧基、C1~C8酰基、C2~C8酯基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、卤素、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基;R3、R4、R5、R6可以相同,也可以不同;
R7为C1~C8烷基、苯基、取代的苯基、萘基、取代的萘基、呋喃基、噻吩基;
所述取代的苯基或萘基中,取代基为C1~C8烷基、C1~C8烷氧基、羟基、C2~C8酰氧基、卤素、氨基、(C1~C8酰基)氨基、二(C1~C8烷基)氨基、C1~C8酰基、C2~C8酯基中的一种或几种;取代基数目为1~5。
2.根据权利要求1所述的螺环膦-羧酸的铱络合物,其特征在于:环辛二烯配体替换为降冰片二烯。
3.根据权利要求1所述的螺环膦-羧酸的铱络合物,其特征在于:
所述的C1~C8烷基为甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、仲戊基、叔戊基、正己基、异己基、新己基、仲己基、叔己基、正庚基、异庚基、新庚基、仲庚基、叔庚基、正辛基、异辛基、新辛基、仲辛基或叔辛基;
所述的C1~C8烷氧基为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、异戊氧基、新戊氧基、仲戊氧基、叔戊氧基、正己氧基、异己氧基、新己氧基、仲己氧基、叔己氧基、正庚氧基、异庚氧基、新庚氧基、仲庚氧基、叔庚氧基、正辛氧基、异辛氧基、新辛氧基、仲辛氧基或叔辛氧基;
所述的C1~C8酰基为甲酰基、乙酰基、丙酰基、正丁酰基、异丁酰基、正戊酰基、异戊酰基、仲戊酰基、新戊酰基、正己酰基、异己酰基、新己酰基、仲己酰基、正庚酰基、异庚酰基、新庚酰基、仲庚酰基、正辛酰基、异辛酰基、新辛酰基、仲辛酰基、1-环丙基甲酰基、1-环丁基甲酰基、1-环戊基甲酰基、1-环己基甲酰基、1-环庚基甲酰基;
所述的C2~C8酰氧基为乙酰氧基、丙酰氧基、正丁酰氧基、异丁酰氧基、正戊酰氧基、异戊酰氧基、仲戊酰氧基、新戊酰氧基、正己酰氧基、异己酰氧基、新己酰氧基、仲己酰氧基、正庚酰氧基、异庚酰氧基、新庚酰氧基、仲庚酰氧基、正辛酰氧基、异辛酰氧基、新辛酰氧基、仲辛酰氧基、1-环丙基甲酰氧基、1-环丁基甲酰氧基、1-环戊基甲酰氧基、1-环己基甲酰氧基、1-环庚基甲酰氧基;
所述的C2~C8酯基为甲氧羰基、乙氧羰基、丙氧羰基、异丙氧羰基、丁氧羰基、异丁氧羰基、正戊氧羰基、异戊氧羰基、新戊氧羰基、仲戊氧羰基、叔戊氧羰基、环戊氧羰基、正己氧羰基、异己氧羰基、新己氧羰基、仲己氧羰基、叔己氧羰基、环己氧羰基、正庚氧羰基、异庚氧羰基、新庚氧羰基、仲庚氧羰基、叔庚氧羰基、环庚氧羰基;
所述的卤代烷基为含氟、氯、溴或碘的卤代烷基。
4.权利要求1所述的螺环膦-羧酸的铱络合物的外消旋体、右旋体和左旋体。
5.根据权利要求1所述的螺环膦-羧酸的铱络合物,其特征在于它是:
7-羧基-7′-二(3,5-二叔丁基苯基)膦基-1,1′-螺双二氢茚.环辛二烯合铱(I)
7-羧基-7′-二(3,5-二甲基苯基)膦基-1,1′-螺双二氢茚.环辛二烯合铱(I)
7-羧基-7′-二(4-甲氧基苯基)膦基-1,1′-螺双二氢茚.环辛二烯合铱(I)
7-羧基-7′-二苯基膦基-1,1′-螺双二氢茚.环辛二烯合铱(I)。
8.根据权利要求7所述的应用,其特征在于将催化剂和底物加入反应釜内管中,加入添加剂和溶剂,密封反应釜并用氢气置换3~10次,充氢气至指定压力,在指定温度下搅拌反应至结束。
9.根据权利要求7所述的应用,其特征在于催化氢化反应条件是:所用溶剂是C1~C6的醇类;催化剂用量为0.001~1mol%;底物浓度为0.001~10.0M;添加剂为异丙胺、叔丁胺、二甲胺、二乙胺、二异丙胺、二异丙基乙基胺、三甲胺、三乙胺、1,8-二氮杂双环[5,4,0]十一-7-烯、1,4-二氮杂二环[2,2,2]辛烷、氢化钠、氢氧化钠、碳酸钠、碳酸氢钠、叔丁醇钠、氢氧化钾、碳酸钾、碳酸氢钾、叔丁醇钾、氢氧化铯、碳酸铯中的一种或几种;反应温度为0~100℃;氢气压力为0.1~10MPa;反应10分钟~48小时。
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