WO2012065571A1 - 手性螺环吡啶胺基膦配体化合物与合成方法及其应用 - Google Patents
手性螺环吡啶胺基膦配体化合物与合成方法及其应用 Download PDFInfo
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- WO2012065571A1 WO2012065571A1 PCT/CN2011/082432 CN2011082432W WO2012065571A1 WO 2012065571 A1 WO2012065571 A1 WO 2012065571A1 CN 2011082432 W CN2011082432 W CN 2011082432W WO 2012065571 A1 WO2012065571 A1 WO 2012065571A1
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 45
- 238000001308 synthesis method Methods 0.000 title claims abstract description 10
- 239000003446 ligand Substances 0.000 title abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000003054 catalyst Substances 0.000 claims abstract description 34
- 150000001728 carbonyl compounds Chemical class 0.000 claims abstract description 13
- 230000003287 optical effect Effects 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 239000007858 starting material Substances 0.000 claims abstract description 4
- -1 2-caiyl Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 22
- 239000003960 organic solvent Substances 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 150000002430 hydrocarbons Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 13
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 13
- 229910052707 ruthenium Inorganic materials 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical group CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000012298 atmosphere Substances 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 239000012018 catalyst precursor Substances 0.000 claims description 9
- 150000003855 acyl compounds Chemical class 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical class O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 6
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical class O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 238000006722 reduction reaction Methods 0.000 claims description 4
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 claims description 3
- JQJBQVRTSMGDJX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxy]decane Chemical compound CCCCCCCCCCOC(C)(C)C JQJBQVRTSMGDJX-UHFFFAOYSA-N 0.000 claims description 3
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 claims description 3
- PAZJFXNRVLDLFO-UHFFFAOYSA-N 4-sulfanylmorpholine Chemical compound SN1CCOCC1 PAZJFXNRVLDLFO-UHFFFAOYSA-N 0.000 claims description 3
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 238000010668 complexation reaction Methods 0.000 claims description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- WLRJHFIRCVDODH-UHFFFAOYSA-L CCO[Sb](O)(Cl)=O Chemical group CCO[Sb](O)(Cl)=O WLRJHFIRCVDODH-UHFFFAOYSA-L 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 2
- NUBSZFGESDICNN-UHFFFAOYSA-N propan-2-yl chlorate Chemical compound CC(C)OCl(=O)=O NUBSZFGESDICNN-UHFFFAOYSA-N 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims 2
- 150000002192 fatty aldehydes Chemical class 0.000 claims 2
- LTRVAZKHJRYLRJ-UHFFFAOYSA-N lithium;butan-1-olate Chemical compound [Li+].CCCC[O-] LTRVAZKHJRYLRJ-UHFFFAOYSA-N 0.000 claims 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 1
- TUDIUWZXQPVWJK-UHFFFAOYSA-N SNS.NN Chemical compound SNS.NN TUDIUWZXQPVWJK-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 230000000536 complexating effect Effects 0.000 claims 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 claims 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 229910052741 iridium Inorganic materials 0.000 abstract description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000011160 research Methods 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- KUXDQQMEFBFTGX-UHFFFAOYSA-N [N].P Chemical compound [N].P KUXDQQMEFBFTGX-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- XQJHRCVXRAJIDY-UHFFFAOYSA-N aminophosphine Chemical compound PN XQJHRCVXRAJIDY-UHFFFAOYSA-N 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 150000003303 ruthenium Chemical class 0.000 description 3
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- YSWYYGKGAYSAOJ-UHFFFAOYSA-N phosphane Chemical compound P.P YSWYYGKGAYSAOJ-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical compound C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 241001251371 Betula chinensis Species 0.000 description 1
- OMHVFMGDWKKSKK-UHFFFAOYSA-N C(C)N(C(C)C)CC.NN Chemical compound C(C)N(C(C)C)CC.NN OMHVFMGDWKKSKK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical group 0.000 description 1
- 150000008365 aromatic ketones Chemical class 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- NQZFAUXPNWSLBI-UHFFFAOYSA-N carbon monoxide;ruthenium Chemical group [Ru].[Ru].[Ru].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] NQZFAUXPNWSLBI-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 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
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- B01J31/189—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 containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Definitions
- the present invention relates to a chiral spiropyridinylaminophosphine ligand compound and a synthetic method therefor.
- the present invention also provides a process for the preparation of a novel spiropyridinium phosphine ligand which is applied to the asymmetric hydrogenation of a carbonyl compound to prepare an optically active compound. Background technique
- chiral phosphine-nitrogen ligands containing an amine group are one of a very important class of chiral ligands.
- Such chiral phosphine-nitrogen ligands can coordinate with many transition metals to form chiral catalysts that have important applications in asymmetric catalytic reactions.
- transition metal catalysts containing an amine group-containing chiral phosphine-nitrogen ligand exhibit good reactivity and enantioselectivity in many asymmetric catalytic reactions (Amoroso, D.; Graham, TW; Guo, R.; Tsang, C.-W.; Abdur-Rashid, K. Aldrich. Chimica. Acta. 2008, 41, 15).
- the chiral catalysts of these chiral phosphatidyl ligands have achieved much lower enantioselectivity in the asymmetric catalytic hydrogenation of mono-ketones than the chiral bisphosphines developed by Noyori et al. /Diamine catalyst.
- the ruthenium catalyst of such a chiral phosphine ligand has higher reactivity than the chiral bismuth-bisphosphine/diamine catalyst in the asymmetric catalytic hydrogenation of ⁇ , ⁇ -unsaturated ketones having an outer double bond. And enantioselectivity; also has a very prominent performance in the asymmetric catalytic hydrogenation of monoarylalkyl ketones.
- the catalyst still has the disadvantage of relatively low conversion number, and its conversion number (substrate to catalyst ratio) in the catalytic hydrogenation reaction of monoketone and ⁇ , ⁇ -unsaturated ketone is much higher than other hands. Sex catalysts, but the maximum is only 10,000, and further improvement is needed.
- the object of the present invention is to provide a novel chiral spiropyridinium phosphine ligand compound and a synthesis method thereof, and the use thereof as a chiral ligand for ruthenium catalyzed carbonyl
- asymmetric catalytic hydrogenation of compounds i.e., in the asymmetric hydrogenation of ruthenium carbonyl compounds including arylalkyl ketones, alkenones, ketoesters, high yields (>90%) and Enantioselectivity (up to 99.9% ee).
- the activity of the reaction is also high, and the amount of the catalyst can be reduced to 0.0001% by mole.
- the synthesis process step of the invention has a single unit and high yield; the obtained chiral spiropyridinium phosphine compound is a very efficient chiral ligand.
- the chiral spiropyridinium phosphine ligand provided by the present invention is a compound having the structure of the formula I, or a racemic or optically active or a catalytically acceptable salt thereof.
- R 1 is a d-C 8 chain hydrocarbon group or a saturated cyclic hydrocarbon group or a cycloalkenyl group, a phenyl group, a substituted phenyl group, a 1-naphthyl group, a 2-caiyl group, a heteroaryl group, a furyl group or a thiol group.
- the substituent on the substituted phenyl group is a halogen, a hydrocarbon group of d to C 8 , an alkoxy group, the number of substituents is 1 to 5, and the heteroaryl group is pyridyl.
- R 2 , R 3 , R 4 , R 5 are H, C1 to C8 alkyl or alkoxy, phenyl, substituted phenyl, 1-caiyl, 2-naphthyl, heteroaryl, furyl or thienyl
- the substituent on the substituted phenyl group is a hydrocarbon group of a d to C 8 , an alkoxy group, the number of substituents is 1 to 5, and the heteroaryl group is a pyridyl group; or R 2 to R 3 , R 4 to R 5 combined into a C3 ⁇ C7 aliphatic ring, an aromatic ring;
- R 2 , R 3 , R 4 , R 5 may be the same or different;
- two adjacent R 6 or two adjacent R 7 may be combined into a C3 ⁇ C7 aliphatic ring or an aromatic ring, and R 6 and R 7 may be the same or different;
- R 8 , 1 9 are 11, halogen, C1 to C8 alkyl, C1 to C8 alkoxy, phenyl, substituted phenyl,
- a 1-naphthyl group, a 2-naphthyl group, a heteroaryl group, a furyl group or a thiol group wherein the substituent on the substituted phenyl group is a halogen, a hydrocarbon group of d to C 8 , an alkoxy group, and the number of substituents is 1.
- R 1 Is H, d ⁇ C 8 alkyl, phenyl, substituted phenyl, 1-caiyl, 2-caiyl, heteroaryl, furyl or silyl, the substituent on the substituted phenyl is d
- the hydrocarbon group and the alkoxy group of ⁇ C 8 have a substituent number of 1 to 5, and the heteroaryl group is a pyridyl group.
- R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 1 are simultaneously H, and R 1 is a phenyl group or a substituted benzene. group, a substituted phenyl group the said substituted group is halogen, d ⁇ C hydrocarbon group or an alkoxy group. 8, the number of substituents is 1 ⁇ 5; R 9 is H, broad halo, C C alkyl.
- R 9 may be a C 3 to C 7 aliphatic ring Or an aromatic ring.
- the present invention also specifically provides a typical compound of a chiral spiropyridinylaminophosphine ligand having the structure shown below, or a racemate or an optical isomer thereof, or a catalytically acceptable salt thereof:
- the present invention also provides a method for synthesizing the chiral spiropyridinium phosphine compound, which is characterized by the racemic or optically active compound 7-diaryl/alkane represented by formula II having a chiral spiroindoline skeleton.
- the phosphinyl-7'-amino-hydrazine, hydrazine-spirobihydroindole is used as a starting material by the following reaction formula:
- R ⁇ R 10 and the values of ⁇ and m are as defined in claim 1.
- the racemic or optically active compound 7-diaryl/alkylphosphino-7'-amino-oxime of the formula II is synthesized by the literature method ( Jian-Bo Xie, Jian -Hua Xie, Xiao-Yan Liu, Wei-Ling Kong, Shen Li, Qi-Lin Zhou, J. Am. Chem. Soc. 2010 132, 4538; Zhou Qilin, Xie Jianhua, Xie Jianbo, Wang Lixin, CN 101671365A).
- the first step is a first step:
- Synthesis Method 1 Racemic or optically active 7-diaryl/alkylphosphino-7'-amino-oxime, ⁇ -spiroindane having the structure of formula II in the presence of an organic solvent and a reducing reagent
- the racemic ratio of racemic or optically active 7-diaryl/alkylphosphino-7'-amino-oxime, ruthenium-spiroindane II, pyridinaldehyde and reducing reagent is 1: 1-5: 1-10 ;
- the reaction temperature is 0 ⁇ 120 °C.
- Step 2 Substituting the above-mentioned pyridinal, pyridinyl chloride, pyridinic acid with a fat or an aromatic aldehyde, an acid chloride or a carboxylic acid according to the above synthetic method or step, and using a snail containing a hydrogen atom on the synthesized nitrogen atom
- the organic solvent may be decyl alcohol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, diphenylbenzene, decyl tert-butyl ether, diethyl ether, dioxane, hydrazine, hydrazine - two a mixed solvent of one or a combination of mercapto amide and disulfoxide;
- the reducing agent may be lithium aluminum hydride, sodium borohydride, sodium triacetylborohydride or sodium nitrile borohydride;
- the base is an organic base or an inorganic base, wherein the organic base may be pyridine, triethylamine, tributylamine, fluorenyl-mercaptomorpholine or hydrazine, hydrazine-diethylisopropylamine; the inorganic base may be hydrogen Sodium oxide, potassium hydroxide, sodium carbonate
- the chiral spiropyridinylaminophosphine compound of the invention can be used as a chiral ligand for asymmetric catalytic reaction, and the compound can be used as a chiral ligand with transition metals such as ruthenium, osmium, iridium, palladium, copper, iron and nickel.
- the metal precursor forms a corresponding transition metal complex and is formed as a chiral catalyst for use in asymmetric reactions, especially in ruthenium-catalyzed carbonyl compounds including arylalkyl ketones, alkenones, ketoesters.
- the chiral spiropyridinium phosphine ligand is firstly complexed with the ruthenium catalyst precursor for 0.5-4 hours, and then at a hydrogen atmosphere at a pressure of 0.1-10 MPa.
- the hydrogenation of the chiral catalyst can be obtained by stirring the reaction for 0.1 to 3 hours; or the complexation reaction of the chiral spiropyridinium phosphine ligand with the ruthenium catalyst precursor in an organic solvent for 0.5-4 hours, and desolvation is obtained.
- the complex, the complex is further stirred in the organic solvent in a hydrogen atmosphere at a pressure of 0.1 to 10 MPa for 0.1 to 3 hours to obtain a chiral catalyst.
- the chiral catalyst prepared can be used for the asymmetric catalytic hydrogenation of a carbonyl compound, and the reaction is described as follows:
- a carbonyl compound or a base is added from the reaction solution or solid obtained above as a catalyst, and the reaction is stirred for 0.1 to 24 hours under a hydrogen atmosphere at a pressure of 0.1 to 10 MPa to obtain a chiral alcohol compound.
- the catalyst is used in an amount of 0.0001 to 5 mol%; the substrate concentration is 0.001 to 10.0 M; the alkali is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium ethoxide, potassium ethoxide, sodium t-butoxide, and tert-butyl Potassium alkoxide, lithium t-butoxide, triethylamine, tributylamine or N-mercaptomorpholine; alkali concentration is 0.005M-1.0M; reaction temperature is 0-80 °C.
- the above organic solvent is one of decyl alcohol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, decyl tert-butyl ether, dioxane, DMF, DMSO or a mixture of several thereof. Solvent.
- the chiral spiropyridinylaminophosphine compound provided by the present invention has a compound of the formula I, or a racemate or an optical isomer thereof, or a catalytically acceptable salt thereof, and the main structural feature is a chiral spiroindoline a framework which can be used as a chiral ligand for the asymmetric catalytic hydrogenation of ruthenium-catalyzed carbonyl compounds, ie, the asymmetric hydrogenation of carbonyl compounds including arylalkyl ketones, ketenes and ketoesters High yield ( >90%) and enantioselectivity (up to 99.9%) Ee).
- the activity of the reaction is also high, and the amount of the catalyst can be reduced to 0.0001% by mole.
- the synthetic process step of the invention has a single unit and high yield; the obtained chiral spiropyridinium phosphine compound is a very efficient chiral ligand.
- Example 1 white solid, yield 96%.
- Example 1 white solid, yield 96%.
- the product is a structure in which the ester is exchanged to a lactone after hydrogenation; b
- the reaction is carried out at 0 °C.
- the chiral spiropyridinium phosphine phosphine ligand compounds and methods for synthesizing the same, and the use thereof, have been described by way of example, and those skilled in the art will be able to devise the invention as described herein without departing from the spirit, scope and scope of the invention.
- the chiral spiropyridinylaminophosphine ligand compound, the synthesis method and its application are modified or modified and combined to achieve the present technology. It is to be understood that all such alternatives and modifications are obvious to those skilled in the art and are considered to be included in the spirit, scope and content of the invention.
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EP11842107.2A EP2641910B1 (en) | 2010-11-19 | 2011-11-18 | Chiral spiro-pyridylamidophosphine ligand compound, synthesis method therefor and application thereof |
ES11842107.2T ES2641313T3 (es) | 2010-11-19 | 2011-11-18 | Compuesto de ligando espiro-piridilamidofosfina quiral, procedimiento de síntesis para el mismo y aplicación del mismo |
JP2013539127A JP5923105B2 (ja) | 2010-11-19 | 2011-11-18 | キラルスピロ−ピリジルアミドフォスフィン配位子化合物、その合成方法及びその利用 |
US13/885,051 US8962839B2 (en) | 2010-11-19 | 2011-11-18 | Chiral spiro-pyridylamidophosphine ligand compound, synthesis method therefor and application thereof |
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ES2641313T3 (es) | 2017-11-08 |
US8962839B2 (en) | 2015-02-24 |
EP2641910A1 (en) | 2013-09-25 |
CN102040625B (zh) | 2013-09-25 |
JP2014501719A (ja) | 2014-01-23 |
JP5923105B2 (ja) | 2016-05-24 |
EP2641910B1 (en) | 2017-06-28 |
US20130225822A1 (en) | 2013-08-29 |
CN102040625A (zh) | 2011-05-04 |
EP2641910A4 (en) | 2014-05-21 |
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