CN115124460B - 含配位单元的联萘轴手性配体及其制备方法和用途 - Google Patents
含配位单元的联萘轴手性配体及其制备方法和用途 Download PDFInfo
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- CN115124460B CN115124460B CN202210936811.7A CN202210936811A CN115124460B CN 115124460 B CN115124460 B CN 115124460B CN 202210936811 A CN202210936811 A CN 202210936811A CN 115124460 B CN115124460 B CN 115124460B
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- China
- Prior art keywords
- substituted phenyl
- binaphthyl
- compound
- butyl
- coordination unit
- Prior art date
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- 239000003446 ligand Substances 0.000 title claims abstract description 82
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 36
- -1 binaphthol amine Chemical class 0.000 claims abstract description 170
- 238000006243 chemical reaction Methods 0.000 claims abstract description 53
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- ZAPYLSLVQJQGEY-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalen-2-amine Chemical class C1=CC=C2C(C3=C4C=CC=CC4=CC=C3N)=CC=CC2=C1 ZAPYLSLVQJQGEY-UHFFFAOYSA-N 0.000 claims abstract description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 25
- 239000003960 organic solvent Substances 0.000 claims description 25
- 150000001879 copper Chemical class 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 16
- 239000003513 alkali Substances 0.000 claims description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 14
- 230000002194 synthesizing effect Effects 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 10
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 9
- 229940045803 cuprous chloride Drugs 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 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 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 7
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
- QYJPSWYYEKYVEJ-FDGPNNRMSA-L copper;(z)-4-oxopent-2-en-2-olate Chemical compound [Cu+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O QYJPSWYYEKYVEJ-FDGPNNRMSA-L 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000008096 xylene Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 5
- 229940125898 compound 5 Drugs 0.000 claims description 5
- 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 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002178 anthracenyl group Chemical class C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 230000000536 complexating effect Effects 0.000 claims description 4
- 229940125773 compound 10 Drugs 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 4
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 239000012495 reaction gas Substances 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- ZKXWKVVCCTZOLD-UHFFFAOYSA-N copper;4-hydroxypent-3-en-2-one Chemical compound [Cu].CC(O)=CC(C)=O.CC(O)=CC(C)=O ZKXWKVVCCTZOLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 2
- 239000001569 carbon dioxide Substances 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 2
- 229940076286 cupric acetate Drugs 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229910052743 krypton Inorganic materials 0.000 claims description 2
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052754 neon Inorganic materials 0.000 claims description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 150000003623 transition metal compounds Chemical class 0.000 claims description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 claims 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims 1
- PBRXKNKPUMMYPO-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-2-methylpropane Chemical compound CC(C)C[O] PBRXKNKPUMMYPO-UHFFFAOYSA-N 0.000 claims 1
- PPZCNAWYKNWRDD-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-3-methylbutane Chemical compound CC(C)CC[O] PPZCNAWYKNWRDD-UHFFFAOYSA-N 0.000 claims 1
- QOOQLKSEGVNYLA-UHFFFAOYSA-N 1-$l^{1}-oxidanylbutane Chemical compound CCCC[O] QOOQLKSEGVNYLA-UHFFFAOYSA-N 0.000 claims 1
- JAVBBFXUGDCHLZ-UHFFFAOYSA-N 1-$l^{1}-oxidanylpropane Chemical compound CCC[O] JAVBBFXUGDCHLZ-UHFFFAOYSA-N 0.000 claims 1
- ZOAMZFNAPHWBEN-UHFFFAOYSA-N 2-$l^{1}-oxidanylpropane Chemical compound CC(C)[O] ZOAMZFNAPHWBEN-UHFFFAOYSA-N 0.000 claims 1
- AELZBYQHJCEGBO-UHFFFAOYSA-N CC(C)(C)C[O] Chemical compound CC(C)(C)C[O] AELZBYQHJCEGBO-UHFFFAOYSA-N 0.000 claims 1
- 229940125797 compound 12 Drugs 0.000 claims 1
- MEUKEBNAABNAEX-UHFFFAOYSA-N hydroperoxymethane Chemical compound COO MEUKEBNAABNAEX-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 229910010271 silicon carbide Inorganic materials 0.000 claims 1
- DVWQNBIUTWDZMW-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalen-2-ol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=CC=CC2=C1 DVWQNBIUTWDZMW-UHFFFAOYSA-N 0.000 abstract description 22
- 239000003054 catalyst Substances 0.000 abstract description 12
- 239000000758 substrate Substances 0.000 abstract description 11
- 238000011914 asymmetric synthesis Methods 0.000 abstract description 10
- 229910052723 transition metal Inorganic materials 0.000 abstract description 5
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical class C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 abstract 1
- HIXQCPGXQVQHJP-UHFFFAOYSA-N nobin Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3N)=C(O)C=CC2=C1 HIXQCPGXQVQHJP-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 122
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Substances 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000005691 oxidative coupling reaction Methods 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- 125000001769 aryl amino group Chemical group 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 229950011260 betanaphthol Drugs 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 150000005347 biaryls Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 125000001624 naphthyl group Chemical class 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 125000001725 pyrenyl group Chemical class 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Chemical group 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000004780 naphthols Chemical class 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 125000005561 phenanthryl group Chemical class 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
- 150000004786 2-naphthols Chemical class 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000662429 Fenerbahce Species 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- PDZKZMQQDCHTNF-UHFFFAOYSA-M copper(1+);thiocyanate Chemical compound [Cu+].[S-]C#N PDZKZMQQDCHTNF-UHFFFAOYSA-M 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- YRNNKGFMTBWUGL-UHFFFAOYSA-L copper(ii) perchlorate Chemical compound [Cu+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O YRNNKGFMTBWUGL-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- FLGPRDQFUUFZBL-UHFFFAOYSA-N formaldehyde;naphthalen-1-ol Chemical compound O=C.C1=CC=C2C(O)=CC=CC2=C1 FLGPRDQFUUFZBL-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- KVRSDIJOUNNFMZ-UHFFFAOYSA-L nickel(2+);trifluoromethanesulfonate Chemical compound [Ni+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F KVRSDIJOUNNFMZ-UHFFFAOYSA-L 0.000 description 1
- BFSQJYRFLQUZKX-UHFFFAOYSA-L nickel(ii) iodide Chemical compound I[Ni]I BFSQJYRFLQUZKX-UHFFFAOYSA-L 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- 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
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2217—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
-
- 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
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
-
- 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
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
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Abstract
本发明公开了一种含配位单元的联萘轴手性配体及其制备方法，以及一种络合物和其在不对称合成手性联萘酚衍生物、联萘胺衍生物和联萘酚胺衍生物中的应用。该含配位单元A的联萘轴手性配体具有以下通式(Ⅰ)的结构：
Description
技术领域
本发明属于不对称合成化学领域，具体涉及一类新型含配位单元的联萘轴手性配体及其制备方法和用途，该类配体与过渡金属所形成的催化剂可用于2-萘酚及其衍生物的不对称氧化偶联反应、联萘胺及其衍生物和联萘酚胺及其衍生物的不对称合成中，具有很高的催化活性和对映选择性。
背景技术
联芳基轴手性化合物不仅广泛存在于天然产物和药物分子中，也经常作为手性源用来合成多种轴手性配体和催化剂，在不对称合成领域扮演着重要角色。自Noyori等人开创性地发展了联萘双膦配体(BINAP)后，新型联芳基轴手性配体不断被开发出来并且应用在过渡金属催化的不对称合成反应中。(Noyori,R.et al.J.Am.Chem.Soc.1979,101,3129-3131；Tang,W.；Zhang,X.Chem.Rev.2003,103,3029-3070；Yudin,A.K.etal.Chem.Rev.2003,103,3155-3212；Brunel,J.M.Chem.Rev.2005,105,857–897)。尽管手性配体/催化剂在不对称合成领域已经取得了长足发展，但是在催化不对称诱导中真正的优势配体骨架并不多。早期的有机膦配体在不对称氢化还原反应中表现出了良好的手性诱导效果，但是仍有许多不对称反应难以通过有机膦配体实现。随后一系列的双齿氮膦配体被开发出来，在一些不对称催化反应中明显地提高了催化活性和对映选择性，但是双齿氮膦配体的后期修饰往往受到局限。因此设计发展具有多种手性控制环境和催化模式的新型配体和催化剂在不对称合成化学中具有重要理论意义和实用价值。
联萘酚(BINOL)、联萘酚胺(NOBIN)、联萘胺(BINAM)是三类非常重要的轴手性分子，广泛应用于材料化学和不对称合成化学等领域。然而目前通过直接芳基碳氢/碳氢不对称偶联获得高光学纯度的萘酚(BINOL)、联萘酚胺(NOBIN)和联萘胺(BINAM)及其衍生化合物仍然非常具有挑战性。现有的手性配体和催化剂通常存在收率和对映选择性低以及底物普适性不好等问题，例如Chien-Tien Chen发展的羟基萘甲醛与氨基酸缩合所得到的三齿配体的钒络合物可催化2-萘酚及其衍生物的不对称氧化偶联反应合成联萘酚(BINOL)，最高e.r.值只有84:16并且底物2-萘酚的适用范围非常有限且对映选择性普遍偏低。如图1所示，虽然Chen Chien-Tien也研究了该催化剂在2-萘胺的不对称氧化偶联合成联萘胺(BINAM)和2-萘胺与2-萘酚不对称氧化偶联合成联萘酚胺(NOBIN)的反应中的催化效果，但是对映选择性非常低，e.r.值分别只有55:45和66.5:33.5，并且所研究的底物只有没有任何取代基的2-萘胺和2-萘酚(C.-T.Chen,et al.Org.Lett.2001,3,869–872)。MarisaC.Kozlowski和Koichi Mikami也分别报道了手性含氮配体与碘化亚铜所制备的催化剂，催化2-萘胺的不对称氧化偶联合成联萘胺(BINAM)，但是收率和e.r.值都很低，收率分别只有26％和50％，e.r.值分别只有47:53和66:34(M.C.Kozlowski,et al.J.Org.Chem.2003,68,5500-5511；K.Mikami,et al.Chirality 2010,22,224–228)。截止到目前，无论是国内还是国际上报道的手性配体和催化剂中，尚未有能以高收率、高对映选择性和广泛的底物适用性催化芳基碳氢/碳氢不对称偶联并且同时合成联萘酚(BINOL)、联萘酚胺(NOBIN)和联萘胺(BINAM)这三类重要的轴手性分子衍生物的体系。因此，发展新型手性配体和催化剂从而发展多样性的联芳基轴手性分子(尤其是联萘酚、联萘酚胺和联萘胺)的不对称合成方法，具有很高的实际应用价值。
发明内容
本发明的目的是提供一类新型含配位单元A的联萘轴手性配体(I)。
本发明的目的另一目的是提供一种上述手性配体的合成方法。
本发明的目的还在于提供上述手性配体的用途，即与过渡金属形成催化剂，用于联萘酚(BINOL)、联萘酚胺(NOBIN)和联萘胺(BINAM)及其衍生物的不对称合成。
本发明提供一种含配位单元的联萘轴手性配体，其特征在于，所述联萘轴手性配体如下述通式(Ⅰ)所示：
在所述通式(Ⅰ)中：
n为氧原子与配位单元通过共价键连接碳原子的个数，n为0或1；
R1选自羟基、氨基、羧基、巯基、C1-7烷基-胺基、磺酸基、芳基-胺基、C1-7烷基-氧基、芳基-氧基、硅烷基-氧基、硅芳基-氧基、酯基以及芳基-膦基中的任一种；
R2-R7分别独立地选自氢、卤素、C1-6烷基、环烷基、芳基、杂芳基、硝基、酯基、氰基、醛基、硅烷基-氧基以及硅芳基-氧基中的任一种；
所述配位单元A选自通式1a、通式1b、通式1c以及通式1d中的任一种：所述通式1a、通式1b、通式1c以及通式1d如下所示：
所述R8、R17、R18分别独立地选自氢、羟基、氨基、C1-7烷基-氧基、芳基-氧基、C1-7烷基-胺基以及芳基-胺基中的任一种；
R9-R16和R19-R30分别独立地选自氢、卤素、烷基、芳基以及杂芳基中的任一种。
用﹡标注的轴手性为R构型或者S构型、或者是外消旋的；
在本发明一优选实验方案中，当所述R1为C1-7烷基-胺基时，所述C1-7烷基-胺基为甲基胺基、乙基胺基、正丙基胺基、异丙基胺基、正丁基胺基、异丁基胺基、正戊基胺基、异戊基胺基、新戊基胺基或苄胺基；当所述R1为芳基-胺基时，所述芳基-胺基为苯基胺基、甲基取代的苯基胺基、甲氧基取代的苯基胺基、叔丁基取代的苯基胺基、氟取代的苯基胺基、萘基胺基、蒽基胺基、菲基胺基或芘基胺基；当所述R1为C1-7烷基-氧基时，所述C1-7烷基-氧基为甲基氧基、乙基氧基、正丙基氧基、异丙基氧基、正丁基氧基、异丁基氧基、正戊基氧基、异戊基氧基、新戊基氧基或苄氧基；当所述R1为芳基-氧基时，所述芳基-氧基为苯基氧基、甲基取代的苯基氧基、三氟甲基取代的苯基氧基、甲氧基取代的苯基氧基、叔丁基取代的苯基氧基、氟取代的苯基氧基、萘基氧基、蒽基氧基、菲基氧基或芘基氧基；当所述R1为硅烷基-氧基时，所述硅烷基-氧基为甲基硅基氧基、乙基硅基氧基、正丙基硅基氧基、异丙基硅基氧基、正丁基硅基氧基、异丁基硅基氧基、正戊基硅基氧基、异戊基硅基氧基或新戊基硅基氧基；当所述R1为硅芳基-氧基时，所述硅芳基-氧基为苯基硅基氧基、甲基取代的苯基硅基氧基、三氟甲基取代的苯基硅基氧基、甲氧基取代的苯基硅基氧基、叔丁基取代的苯基硅基氧基或氟取代的苯基硅基氧基；当所述R1为芳基-膦基时，所述芳基-膦基为苯基膦基、甲基取代的苯基膦基、甲氧基取代的苯基膦基、三氟甲基取代的苯基膦基或叔丁基取代的苯基膦基；
在本发明一优选实验方案中，当所述R2-R7分别独立地为C1-6烷基时，所述C1-6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、新戊基或己基；当所述R2-R7分别独立地为环烷基时，所述环烷基为环丙烷基、环丁烷基、环戊烷基、环己烷基、环庚烷基或环辛烷基；当所述R2-R7分别独立地为烷基-氧基时，所述烷基氧基为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁基氧基、异丁基氧基或叔丁基氧基；当所述R2-R7分别独立地为芳基时，所述芳基为苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、三氟甲基取代的苯基、甲氧基取代的苯基、乙氧基取代的苯基、叔丁基氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基、碘取代的苯基、萘基、蒽基、菲基或芘基；当所述R2-R7分别独立地为杂芳基时，所述杂芳基为呋喃基、噻吩基、吲哚基或吡啶基；
在本发明一优选实验方案中，当所述R8、R17、R18分别独立地为C1-7烷基-氧基时，所述C1-7烷基-氧基为甲基氧基、乙基氧基、正丙基氧基、异丙基氧基、正丁基氧基、异丁基氧基、正戊基氧基、异戊基氧基、新戊基氧基或苄氧基；当所述R8、R17、R18分别独立地为芳基-氧基时，所述芳基-氧基为苯基氧基、甲基取代的苯基氧基、三氟甲基取代的苯基氧基、甲氧基取代的苯基氧基、叔丁基取代的苯基氧基、氟取代的苯基氧基、萘基氧基、蒽基氧基、菲基氧基或芘基氧基；当所述R8、R17、R18分别独立地为C1-7烷基-胺基时，所述C1-7烷基-胺基为甲基胺基、乙基胺基、正丙基胺基、异丙基胺基、正丁基胺基、异丁基胺基、正戊基胺基、异戊基胺基、新戊基胺基或苄胺基；当所述R8、R17、R18分别独立地为芳基-胺基时，所述芳基-胺基为苯基胺基、甲基取代的苯基胺基、三氟甲基取代的苯基胺基、甲氧基取代的苯基胺基、叔丁基取代的苯基胺基、氟取代的苯基胺基、萘基胺基、蒽基胺基、菲基胺基或芘基胺基；
在本发明一优选实验方案中，当所述R9-R16、R19-R30为烷基时，所述烷基为甲基、乙基、正丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基、正戊基、异戊基、新戊基或己基；当所述R9-R16、R19-R30为芳基时，所述芳基为苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、三氟甲基取代的苯基、甲氧基取代的苯基、乙氧基取代的苯基、叔丁基氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基、碘取代的苯基、萘基、蒽基、菲基或芘基；当所述R9-R16、R19-R30分别独立地为杂芳基时，所述杂芳基为呋喃基、噻吩基、吲哚基、吡啶基或喹啉基。
本发明还提供一种所述含配位单元的联萘轴手性配体的制备方法，其特征在于，所述联萘轴手性配体的配位单元分别为通式1a、通式1b、通式1c以及通式1d时，制备方法如下：
(1)配位单元为通式1a的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物b溶解在有机溶剂中，在碱的作用下反应1-48小时，即可；
(2)配位单元为通式1b的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物c溶解在有机溶剂中，在碱的作用下反应1-60小时，即可；
(3)配位单元为通式1c的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物d溶解在有机溶剂中，在碱的作用下0-100℃反应1-60小时，即可；
(4)配位单元为通式1d的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物e在惰性气体保护下溶解在有机溶剂中，在铜盐、碱、草酰胺配体的作用下0-150℃反应1-60小时，即可；
所述化合物中的Y为氯原子、溴原子或碘原子；
在本发明中，所述的有机溶剂为有机合成领域常规使用的溶剂，所述有机溶剂为甲醇、乙醇、异丙醇、正丁醇、丙酮、二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷、乙醚、甲基叔丁基醚、四氢呋喃、1,4-二氧六环、苯、甲苯、二甲苯、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、二甲基亚砜中的一种或几种；优选甲苯。
在本发明中，所述合成方法中的铜盐为常规金属铜盐，所述铜盐如氯化亚铜、溴化亚铜、碘化亚铜或氰化亚铜。
在本发明中，所述惰性气体包括氮气、氩气、氦气、氖气以及氪气中的一种或几种；
在本发明中，所述的碱为有机合成领域常规使用的碱，包括无机碱氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、磷酸钾、磷酸钠、碳酸铯、甲醇钠、叔丁醇钾、叔丁醇钠、氢化钠、氢化钙或有机碱正丁基锂、仲丁基锂、叔丁基锂、二异丙基氨基锂、1,8-二氮杂双环[5.4.0]十一碳-7-烯、三乙胺或吡啶。
在本发明中，所述的反应温度可为有机合成领域该类反应常规的反应温度，例如100℃。
在本发明中，所述的反应时间可为有机合成领域该类反应常规的反应时间，所述反应时间为1-60h，例如24h。
在本发明中，所述的反应式化合物a在所述有机溶剂中的摩尔浓度为0.01-2mol/L，例如，0.5mol/L。
在本发明中，所述的合成反应结束后还包括减压脱溶。
在本发明中，所述的合成反应结束后还包括淬灭过程。所述的淬灭所用的溶液可为有机合成领域该类反应常规的淬灭溶液，例如饱和氯化铵溶液或氢氧化钠溶液。
在本发明中，所述的合成反应结束后还包括后处理步骤，所述的后处理步骤可为本领域中常规的后处理步骤，所述后处理步骤包括萃取、洗涤、干燥、柱层析步骤中的一步或多步。
在本发明中，所述的萃取剂可为有机合成领域常规萃取剂，包括乙酸乙酯、二氯甲烷、氯仿、乙醚。所述洗涤所用溶液可为本领域常规洗涤溶液，例如饱和氯化钠溶液；所述的干燥可采用本领域常规的干燥剂，如无水硫酸钠、无水硫酸镁；所述的柱层析可为有机合成领域常规硅胶柱层析，所述柱层析所用洗脱剂可为有机合成领域常规洗脱剂，如石油醚、二氯甲烷、乙酸乙酯或甲醇中的一种或几种的混合物。
在本发明中还提供一种络合物，如通式(Ⅰ)所述的任一含配位单元的联萘轴手性配体和过渡金属化合物所形成的络合物，所述过渡金属化合物包括碘化亚铜、溴化亚铜、氯化亚铜、三氟甲磺酸铜、乙酰丙酮铜、六氟磷酸四乙腈铜、碘化镍、氯化镍、三氟甲磺酸镍、三氯化铁、三溴化铁、三氟甲磺酸亚铁、四(三苯基膦)钯、三(二亚苄基丙酮)二钯、醋酸钯或氯化钯。将所述的配位单元为1d的联萘轴手性配体，其中配位单元中R1为羟基、R30为蒽基，R2-R7、R24-R29为氢，与氯化亚铜络合，所得到的络合物单晶结构如图10所示。
本发明还提供一种合成联萘酚化合物的方法，包括如下步骤，在反应气体下，将所述的配位单元为1a的联萘轴手性配体，其中R1为羟基、R2、R5为对叔丁基苯基、R8为羟基，R3-R4、R6-R7、R9-R11为氢，金属铜盐和碱在有机溶剂中络合，将化合物5进行如下式反应得到化合物6，
其中，R31-R33分别独立为氢、烷基、芳基、羧基、酯基、醛基、酰基、胺基、卤素或硝基；
用*标注的手性轴为S构型或R构型或者是外消旋的。
本发明还提供一种合成联萘胺衍生物化合物的方法，包括如下步骤，在有机溶剂中，将所述的配位单元为1d的联萘轴手性配体，其中配位单元中R1为羟基、R30为蒽基，R2-R7、R24-R29为氢，与金属铜盐络合，将化合物7与化合物8进行如式反应得到化合物9，
其中，R34分别选自烷基、芳基、杂芳基；R35-R39分别独立为氢、烷基、芳基、羧基、酯基、醛基、酰基、胺基、卤素或硝基；
用*标注的手性轴为S构型或R构型或者是外消旋的。
本发明还提供一种合成联萘酚胺衍生物化合物的方法，包括如下步骤，在有机溶剂中，将所述的配位单元为1d的联萘轴手性配体，其中配位单元中R1为三异丙基硅基氧基、R30为蒽基，R2-R7、R24-R29为氢，与金属铜盐络合，将化合物7与化合物5进行如式反应得到化合物10，
其中，R31-R36和*的定义如上述两个合成方法所述；
在本发明中，当所述R31-R37为烷基时，所述烷基为甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基或环己基。
在本发明中，当所述R31-R37为芳基时，所述芳基为苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、三氟甲基取代的苯基、甲氧基取代的苯基、乙氧基取代的苯基、叔丁基氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基、萘基、蒽基、菲基或芘基。
在本发明中，当所述R31-R37分别选自杂芳基时，所述杂芳基为呋喃基、噻吩基、吲哚基或吡啶基。
在本发明中，所述有机溶剂为有机合成领域常规使用的溶剂，包括甲醇、乙醇、异丙醇、正丁醇、丙酮、二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷、乙醚、甲基叔丁基醚、四氢呋喃、1,4-二氧六环、苯、甲苯、二甲苯、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮或二甲基亚砜；优选甲苯、1,2-二氯乙烷。
在本发明中，所述反应气体为氧气、一氧化碳、二氧化碳或空气。
在本发明中，所述金属铜盐可以是氯化铜、溴化铜、氯化亚铜、溴化亚铜、碘化亚铜、醋酸铜、乙酰丙酮铜、高氯酸铜、三氟乙酸铜、四氟硼酸铜、六氟磷酸根四乙腈铜、氰化亚铜、硫氰酸亚铜、噻吩-2-甲酸亚铜、氧化亚铜；优选碘化亚铜、乙酰丙酮铜或六氟磷酸根四乙腈铜。
在本发明中，所述碱包括无机碱氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、磷酸钾、磷酸钠、碳酸铯、甲醇钠、叔丁醇钾、叔丁醇钠、氢化钠、氢化钙或有机碱正丁基锂、仲丁基锂、叔丁基锂、二异丙基氨基锂、1,8-二氮杂双环[5.4.0]十一碳-7-烯、三乙胺或吡啶；优选碳酸铯。
在本发明中，所述的反应式中化合物5、化合物7和化合物8在所述有机溶剂中的摩尔浓度为0.01～1.0M；例如0.1M。
在本发明中，上述制备联萘酚衍生物的反应中的络合物与碱的摩尔比为：1:1～1:10；例如1:3。
在本发明中，上述制备联萘酚衍生物反应中的金属铜盐与配体的摩尔比为：1:1～1:5；例如1:1.2。
在本发明中，上述制备联萘胺衍生物反应中的金属铜盐与配体的摩尔比为：1:1～1:5；例如1:1.2。
在本发明中，上述制备联萘酚胺衍生物反应中的金属铜盐与配体的摩尔比为：1:1～1:5；例如1:1.2。
在本发明中，上述反应中的反应底物与络合物的摩尔比为：1:0.01～1:0.3；例如1:0.15。
在本发明中，所述的反应温度为-30-50℃；例如25℃。
在本发明中，所述的反应时间为1～72小时；例如48小时。
在本发明实施方案中，所述的反应结束后还包括后处理步骤，所述的后处理步骤可为有机合成领域中常规的后处理步骤，所述后处理步骤包括柱层析步骤。
术语“e.r.”指对映体比例(enantiomeric ratio)
本发明的积极进步效果在于：
本发明提供一种新型含配位单元的联萘轴手性配体，主要结构特征是具有吡啶酰基、喹啉酰基、菲罗啉、联萘基轴等基团，该配体的合成方法以联萘骨架的二酚与吡啶羧酸衍生物、喹啉羧酸衍生物、菲罗啉衍生物为起始原料，在金属铜盐催化剂和碱的作用下使联萘基轴手性基团与各配位单元之间发生亲核取代反应构建碳杂原子键。本发明目标分子结构简洁明了，实验操作简单可大规模制备。在新型轴手性配体的设计以及联芳基轴手性化合物合成方面具有潜在的应用价值。
本发明提供的新型含配位单元的联萘轴手性配体，可作为手性配体与过渡金属铜盐在反应体系中形成催化剂，催化联萘酚(BINOL)、联萘酚胺(NOBIN)和联萘胺(BINAM)及其衍生化合物的不对称合成反应，表现出了良好到优秀的收率(最高达98％)和良好到优秀的对映选择性(e.r.最高达98:2)和反应底物的普适性(至少兼容数十种反应底物)，具有很好的工业应用前景。
附图说明
图1为不对称氧化偶联法合成联萘胺BINAM和联萘酚胺NOBIN的背景技术图；
图2为本发明实施例提供的配位单元为通式1a联萘轴手性配体核磁氢谱图；
图3为本发明实施例提供的配位单元为通式1a联萘轴手性配体核磁碳谱图；
图4为本发明实施例提供的配位单元为通式1b联萘轴手性配体核磁氢谱图；
图5为本发明实施例提供的配位单元为通式1b联萘轴手性配体核磁碳谱图；
图6为本发明实施例提供的配位单元为通式1c联萘轴手性配体核磁氢谱图；
图7为本发明实施例提供的配位单元为通式1c联萘轴手性配体核磁碳谱图；
图8为本发明实施例提供的配位单元为通式1d联萘轴手性配体核磁氢谱图；
图9为本发明实施例提供的配位单元为通式1d联萘轴手性配体核磁碳谱图；
图10为本发明实施例提供的配位单元为1d联萘轴手性配体与金属铜盐的络合物单晶结构图。
具体实施方式
下面通过具体实施例对本发明做进一步详细说明，但不因此限制本发明的范围。
以下各实施例中所使用的仪器和实验材料信息如下：
化学试剂全部采购商品化试剂，试剂来源于Adamas、毕得医药、百灵威等试剂公司。薄层色谱分析(TLC)采用的是SHF254硅胶板，硅胶柱层析所用诺泰硅胶(300-400目)，TLC采用UV光(254nm)。1HNMR和13CNMR使用Bruker AVANCEⅢ400MHz核磁共振仪表征，溶剂为氘代氯仿、氘代甲醇或氘代二甲亚砜。化学位移的单位是ppm,耦合常数的单位是Hz,1HNMR中，δ表示化学位移，s表示单峰，d表示双峰，t表示三重峰，q表示四重峰，m表示多重峰，br表示宽峰。在13CNMR中，δ表示化学位移。高分辨质谱使用JEOC AccuTOF LC-plus 4G设备，离子源采用ESI，或Waters GCT Premier，离子源采用EI。通过岛津LC-20A高效液相色谱和大赛璐Chiralpak、Chiralcel手性柱来测定对映体比例(e.r.)。
实施例1：
选取干燥的50mL圆底烧瓶，加入3,3’-对叔丁基苯基取代的联萘二酚(605mg,1.10mmol)后加入20mL干燥的DMF溶剂溶解，然后置于冰水浴下搅拌10分钟，将一定量的NaH(48mg,1.21mmol)分批加入到反应瓶中，室温搅拌3h后，再分批加入化合物1b(278mg,1.21mmol)搅拌8h后，TLC监测反应是否完全，待原料完全转化后，加入少量的冰水淬灭多余的NaH，然后使用二氯甲烷(3×30mL)溶剂萃取，将合并的有机层用水多次洗涤，最后用盐水洗涤，无水硫酸钠干燥、过滤、减压去除部分溶剂后通过硅胶柱色谱纯化(石油醚/乙酸乙酯＝8/1)得到白色固体(R)-2a(568mg,收率74％)。1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.94(d,J＝8.0Hz,1H),7.81(s,1H),7.79(d,J＝9.2Hz,1H),7.70(d,J＝6.4Hz,1H),7.59(d,J＝8.4Hz,2H),7.48–7.46(m,1H),7.45–7.43(m,2H),7.36–7.28(m,4H),7.25–7.16(m,6H),6.61(d,J＝8.8Hz,1H),5.55(s,1H),4.70(d,J＝14.0Hz,1H),4.62(d,J＝14.4Hz,1H),3.82(s,3H),2.41(s,3H),2.39(s,3H).13C NMR(101MHz,CDCl3)δ165.68,158.33,154.32,149.15,146.25,137.64,137.49,136.93,135.80,135.45,134.73,133.59,133.21,131.58,131.41,130.51,129.85,129.46,129.43,129.41,129.32,129.12,128.34,128.05,126.97,126.79,125.86,125.72,124.89,124.00,123.93,123.87,123.32,116.50,75.22,52.83,21.37,21.36.HRMS(ESI-TOF)m/z Calcd.for C42H34NO4 +[M+H]+:616.2482；Found:616.2481.
实施例2：
制备方法与实施例1相同,淡黄色固体,583mg,收率65％；1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.95(d,J＝8.0Hz,1H),7.82(s,1H),7.81(s,1H),7.73(d,J＝7.6Hz,1H),7.48–7.43(m,1H),7.35–7.20(m,8H),7.09(s,2H),7.03(s,1H),6.98(s,1H),6.64(d,J＝7.6Hz,1H),5.50(s,1H),4.74(d,J＝14.0Hz,1H),4.67(d,J＝14.4Hz,1H),3.84(s,3H),2.36(s,6H),2.34(s,6H).13C NMR(101MHz,CDCl3)δ165.68,158.65,154.34,149.02,146.27,138.36,137.96,137.42,136.87,136.04,133.72,133.24,131.48,131.44,130.74,129.74,129.60,129.38,129.07,128.32,128.06,127.37,127.28,126.91,126.80,125.76,125.72,124.92,123.93,123.87,123.25,116.58,75.31,52.84,21.49.HRMS(ESI-TOF)m/zCalcd.for C44H38NO4 +[M+H]+:644.2794；Found:644.2795.
实施例3：
制备方法与实施例1相同，黄色固体,87mg,收率68％；1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.86(d,J＝8.0Hz,1H),7.73–7.71(m,2H),7.65(d,J＝7.6Hz,1H),7.37(ddd,J＝8.0,6.0,2.0Hz,1H),7.24–7.19(m,4H),7.18(s,2H),7.16–7.10(m,2H),7.02(s,2H),6.55(d,J＝7.6Hz,1H),5.40(br,1H),4.69(d,J＝14.4Hz,1H),4.61(d,J＝14.4Hz,1H),3.78(s,3H),2.24(s,6H),2.22(s,6H),2.14(s,3H),2.12(s,3H).13C NMR(101MHz,CDCl3)δ165.48,158.77,154.47,149.08,145.92,137.16,136.99,136.60,135.92,135.34,135.04,134.69,134.31,133.64,133.12,131.51,131.34,130.67,129.52,129.17,129.07,128.65,128.55,128.36,128.28,128.00,126.80,126.71,125.73,124.93,124.06,123.88,123.82,123.31,116.55,75.16,52.95,20.79,15.40,15.38.HRMS(ESI-TOF)m/z Calcd.for C46H42NO4 +[M+H]+:672.3108；Found:672.3102。
实施例4：
制备方法与实施例1相同，白色固体,258mg,收率76％；1H NMR(400MHz,CDCl3)δ8.08(s,1H),7.99(d,J＝8.4Hz,1H),7.86(s,1H),7.83(d,J＝7.6Hz,1H),7.73(d,J＝9.2Hz,1H),7.59(d,J＝1.6Hz,2H),7.48–7.46(m,2H),7.41–7.29(m,8H),7.24–7.21(m,1H),6.71(d,J＝8.4Hz,1H),5.60(s,1H),4.72(d,J＝14.0Hz,1H),4.61(d,J＝14.4Hz,1H),3.83(s,3H),1.37(s,18H),1.32(s,18H).13C NMR(101MHz,CDCl3)δ165.67,158.75,154.14,151.21,150.81,149.14,146.26,137.48,136.92,136.79,136.56,133.68,133.29,131.60,131.49,129.91,129.10,128.37,128.10,126.83,126.73,125.91,125.77,125.07,124.25,123.95,123.85,123.81,123.31,122.06,121.67,116.52,74.72,52.82,35.05,31.64.HRMS(ESI-TOF)m/z Calcd.for C56H62NO4 +[M+H]+:812.4673；Found:812.4667.
实施例5：
制备方法与实施例1相同，淡黄色固体,250mg,收率78％；1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.94(d,J＝8.0Hz,1H),7.81(s,1H),7.79(d,J＝9.2Hz,1H),7.70(d,J＝6.4Hz,1H),7.59(d,J＝8.4Hz,2H),7.48–7.46(m,1H),7.45–7.43(m,2H),7.36–7.28(m,4H),7.25–7.16(m,6H),6.61(d,J＝8.8Hz,1H),5.55(s,1H),4.70(d,J＝14.0Hz,1H),4.62(d,J＝14.4Hz,1H),3.82(s,3H),2.41(s,1H),2.39(s,1H).13C NMR(101MHz,CDCl3)δ165.68,158.33,154.32,149.15,146.25,137.64,137.49,136.93,135.80,135.45,134.73,133.59,133.21,131.58,131.41,130.51,129.85,129.46,129.43,129.41,129.32,129.12,128.34,128.05,126.97,126.79,125.86,125.72,124.89,124.00,123.93,123.87,123.32,116.50,75.22,52.83,21.37,21.36.HRMS(ESI-TOF)m/z Calcd.for C42H34NO4 +[M+H]+:616.2482；Found:616.2480.
实施例6：
选取25mL的圆底烧瓶，加入化合物(R)-2a(568mg,0.81mmol)后加入10mL的甲醇溶剂溶解，然后加入一定量的KOH水溶液(2mL,2M,4.0mmol)，将反应体系放置于35℃下搅拌3h，TLC监测反应是否完全，待原料完全转化后，使用1M的稀盐酸调节pH到3-4，然后将甲醇溶剂减压蒸馏，再使用乙酸乙酯(3×30mL)溶剂萃取，合并有机层用盐水洗涤，无水硫酸钠干燥、过滤、减压去除部分溶剂后通过重结晶得到淡黄色固体(R)-3a，505mg,收率91％；1HNMR(400MHz,CDCl3)δ8.05(s,1H),7.94(d,J＝8.0Hz,1H),7.82(s,1H),7.77(d,J＝8.0Hz,2H),7.66(d,J＝8.4Hz,2H),7.53–7.44(m,7H),7.40(t,J＝7.8Hz,1H),7.36–7.20(m,4H),7.13(d,J＝8.4Hz,1H),6.71(d,J＝8.0Hz,1H),4.56(d,J＝12.8Hz,1H),4.41(d,J＝12.8Hz,1H),1.36(s,18H).13C NMR(101MHz,CDCl3)δ163.98,156.43,154.08,150.99,150.90,149.02,144.41,138.30,135.51,135.24,134.47,133.41,133.24,131.63,131.53,130.35,130.04,129.29,129.16,129.07,128.40,128.18,127.11,126.80,126.04,125.80,125.75,125.61,125.47,124.80,123.97,123.81,121.96,116.19,74.83,34.76,34.75,31.50,31.47.HRMS(ESI-TOF)m/z Calcd.for C47H44NO4 +[M+H]+:686.3265；Found:686.3255.(图2，图3)
实施例7：
制备方法与实施例6相同，淡黄色固体,480mg,收率82％；1H NMR(400MHz,CDCl3)δ8.05(s,1H),7.97(d,J＝8.0Hz,1H),7.85–7.82(m,3H),7.52–7.44(m,2H),7.38–7.25(m,6H),7.18(d,J＝8.8Hz,1H),7.16(s,2H),7.05(d,J＝7.2Hz,2H),6.76(d,J＝7.6Hz,1H),4.62(d,J＝13.2Hz,1H),4.49(d,J＝13.2Hz,1H),2.39(s,6H),2.38(s,6H).13C NMR(101MHz,CDCl3)δ163.97,156.64,153.88,148.86,144.45,138.58,138.28,138.24,138.01,137.19,135.80,133.57,133.27,131.55,131.43,130.68,129.86,129.77,129.42,129.04,128.39,128.19,127.42,127.19,127.07,126.84,125.96,125.74,125.57,124.84,124.03,123.99,121.87,116.27,74.82,21.52,21.50.HRMS(ESI-TOF)m/z Calcd.forC43H36NO4 +[M+H]+:630.2639；Found:630.2644.
实施例8：
制备方法与实施例6相同，黄色固体,64mg,收率77％；1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.95(d,J＝8.4Hz,1H),7.83–7.80(m,3H),7.48–7.42(m,3H),7.37–7.32(m,5H),7.18–7.13(m,3H),6.76(d,J＝7.6Hz,1H),4.62(d,J＝13.2Hz,1H),4.48(d,J＝13.2Hz,1H),2.34(s,6H),2.33(s,6H),2.23(s,6H).13C NMR(101MHz,CDCl3)δ163.96,156.70,153.98,148.95,144.41,138.24,137.20,136.60,135.74,135.23,134.80,134.14,133.52,133.19,131.61,131.30,130.64,129.68,129.09,128.72,128.49,128.42,128.35,128.15,126.94,126.73,125.91,125.77,125.66,124.87,124.09,123.93,121.77,116.25,74.82,20.83,20.79,15.42,15.40.HRMS(ESI-TOF)m/z Calcd.for C45H40NO4 +[M+H]+:658.2952；Found:658.2951.
实施例9：
制备方法与实施例6相同，白色固体,218mg,收率84％；1H NMR(400MHz,CDCl3)δ8.09(s,1H),7.98(d,J＝8.4Hz,1H),7.87(s,1H),7.82(t,J＝8.2Hz,2H),7.58(s,2H),7.49–7.39(m,7H),7.32(q,J＝7.4Hz,2H),7.26(t,J＝7.4Hz,1H),7.20–7.18(m,1H),6.75(d,J＝8.0Hz,1H),5.60(br,1H),4.62(d,J＝13.2Hz,1H),4.44(d,J＝13.2Hz,1H),1.37(s,18H),1.34(s,18H).13C NMR(101MHz,CDCl3)δ164.01,156.83,153.85,151.37,150.92,149.05,144.47,138.27,137.52,136.59,136.55,133.52,133.31,131.56,131.47,131.44,129.98,129.05,128.37,128.21,126.96,126.74,125.93,125.90,125.50,124.93,124.12,123.93,123.72,122.19,121.93,121.59,116.28,74.50,35.09,35.07,31.66,31.62.HRMS(ESI-TOF)m/z Calcd.for C55H60NO4 +[M+H]+:798.4517；Found:798.4526.
实施例10：
制备方法与实施例6相同，白色固体,197mg,收率79％；1H NMR(400MHz,CDCl3)δ8.03(s,1H),7.92(d,J＝8.0Hz,1H),7.80(s,1H),7.77(d,J＝8.0Hz,2H),7.62(d,J＝7.6Hz,2H),7.45–7.37(m,4H),7.35–7.30(m,2H),7.28–7.12(m,7H),6.72(d,J＝7.6Hz,1H),4.57(d,J＝12.8Hz,1H),4.42(d,J＝13.2Hz,1H),2.39(s,3H),2.38(s,3H).13C NMR(101MHz,CDCl3)δ164.02,156.37,153.92,148.97,144.43,138.31,137.76,137.62,135.51,135.25,134.45,133.40,133.21,131.60,131.39,130.44,129.90,129.49,129.46,129.31,129.27,129.02,128.35,128.14,127.06,126.77,125.99,125.71,125.46,124.75,123.94,123.91,121.98,116.18,74.66,21.32.HRMS(ESI-TOF)m/z Calcd.for C41H32NO4 +[M+H]+:602.2326；Found:602.2324.
实施例11：
向干燥的100mL Schlenk瓶中加入化合物4a-a(0.40g,1.87mmol)、4b(0.51g,1.70mmol)、CuI(97mg,0.51mmol)、草酰胺配体(175mg,0.51mmol)、K3PO4(0.72g,3.40mmol)，将反应体系置换氮气三次并在氮气氛围下通过注射器加入无水DMSO(10mL)，随后将反应混合物在110℃搅拌48小时。冷却至室温后，反应混合物用硅藻土过滤，滤液用二氯甲烷(3×20mL)萃取，将合并的有机相用饱和食盐水洗涤，经Na2SO4干燥后过滤，除去有机溶剂后，将残余物通过硅胶柱色谱纯化，使用石油醚/乙酸乙酯(5:1)作为洗脱剂，得到白色固体(R)-5a,510mg，收率62％；1H NMR(400MHz,CDCl3):δ9.06(dd,J＝4.4,1.6Hz,1H),8.15(dd,J＝8.0,2.0Hz,1H),8.03(d,J＝8.8Hz,1H),8.00(d,J＝8.8Hz,1H),7.95(d,J＝8.0Hz,1H),7.86(d,J＝8.8Hz,1H),7.75(d,J＝8.0Hz,1H),7.66(d,J＝8.8Hz,1H),7.62(d,J＝8.8Hz,1H),7.53(dd,J＝8.4,4.4Hz,1H),7.49(d,J＝9.2Hz,1H),7.45(ddd,J＝8.0,6.0,2.0Hz,1H),7.29(s,1H),7.27(d,J＝2.0Hz,2H),7.24–7.19(m,2H),7.12(ddd,J＝8.4,7.2,1.6Hz,1H),7.08(d,J＝8.8Hz,1H),3.66(s,3H)；13C NMR(101MHz,CDCl3):δ163.09,154.91,150.77,150.13,145.41,145.10,139.25,135.87,134.48,134.13,131.42,129.92,129.83,129.10,129.04,128.24,127.84,126.73,126.45,126.25,125.88,125.65,125.33,125.28,125.23,124.61,123.55,122.91,121.25,117.95,113.22,112.92,56.30；HRMS(ESI-TOF)m/z Calcd.for C33H23N2O2 +[M+H]+:479.1754；Found:479.1743.
实施例12：
制备方法与实施例11相同，白色固体,230mg,收率50％；1H NMR(400MHz,CDCl3):δ8.07–7.91(m,4H),7.84(d,J＝8.8Hz,1H),7.73(d,J＝8.0Hz,1H),7.61(d,J＝8.4,1H),7.55(d,J＝8.4,1H),7.51(d,J＝8.8Hz,1H),7.49–7.40(m,2H),7.29-7.26(m,4H),7.19(t,J＝7.2,Hz 1H),7.11(t,J＝7.6,Hz 1H),7.05(d,J＝8.4Hz,1H),3.66(s,3H)；13C NMR(101MHz,CDCl3):δ163.14,154.91,151.02,150.60,145.00,143.78,139.23,138.60,134.37,134.01,131.42,129.93,129.80,129.02,128.21,127.80,127.61,126.69,126.42,126.26,126.19,125.68,125.64,125.33,125.20,124.11,123.81,123.52,121.33,117.87,113.49,113.31,56.35；HRMS(ESI-TOF)m/z Calcd.for C33H22ClN2O2 +[M+H]+:513.1364；Found:513.1354.
实施例13：
制备方法与实施例11相同，白色固体,60mg,收率56％；1H NMR(400MHz,CDCl3):δ8.15(d,J＝8.0Hz,3H),8.12(dd,J＝8.8Hz,1H),8.03(dd,J＝14.0,8.4Hz,2H),7.88(d,J＝8.8Hz,1H),7.82(d,J＝8.8Hz,2H),7.62(d,J＝8.0Hz,1H),7.58–7.48(m,3H),7.46(d,J＝8.4Hz,1H),7.34(d,J＝7.2Hz,1H),7.32–7.25(m,4H),7.24(s,1H),6.98(t,J＝7.2Hz,1H),6.92(d,J＝8.4Hz,1H),6.61(t,J＝7.6Hz,1H),3.65(s,3H)；13C NMR(101MHz,CDCl3):δ162.90,155.86,155.04,150.87,145.02,144.64,139.10,139.03,136.55,134.46,134.02,131.68,129.72,129.38,129.22,128.98,128.70,128.20,127.79,127.43,127.33,126.69,126.41,126.32,125.74,125.58,125.53,125.35,125.19,123.93,123.37,123.18,119.20,118.65,113.74,112.74,56.79；HRMS(ESI-TOF)m/z Calcd.for C39H27N2O2 +[M+H]+:555.2067；Found:555.2057.
实施例14：
制备方法与实施例11相同，白色固体,175mg,收率51％；1H NMR(400MHz,CDCl3):δ8.16(d,J＝8.4Hz,1H),8.11(d,J＝8.8Hz,1H),8.04(d,J＝8.4Hz,1H),7.98(d,J＝8.4Hz,1H),7.89(d,J＝8.4Hz,1H),7.87–7.81(m,4H),7.63(d,J＝8.0Hz,1H),7.56(dd,J＝14.8,8.4Hz,2H),7.47(d,J＝8.4Hz,1H),7.43(d,J＝7.2Hz,1H),7.30(d,J＝8.8Hz,1H),7.24–7.22(m,2H),6.99–6.72(m,2H),6.90(d,J＝8.4Hz,1H),6.70(t,J＝7.2Hz,1H),3.66(s,3H),2.24(s,6H)；13C NMR(101MHz,CDCl3):δ162.78,156.21,155.06,150.86,144.95,144.66,139.06,138.99,138.22,136.54,134.44,134.02,131.51,131.12,129.72,129.30,129.16,128.98,128.28,127.82,127.31,126.57,126.39,126.22,125.89,125.46,125.37,125.30,125.12,124.03,123.39,122.87,119.52,118.72,113.79,113.06,56.84,21.46；HRMS(ESI-TOF)m/z Calcd.for C41H31N2O2 +[M+H]+:583.2380；Found:583.2382.
实施例15：
制备方法与实施例11相同，黄色固体,99mg,收率78％；1H NMR(400MHz,CDCl3):δ8.51(s,1H),8.32(dd,J＝8.0,3.2Hz,1H),8.02(t,J＝6.8Hz,2H),7.94(dd,J＝8.8,1.6Hz,1H),7.85(d,J＝8.4Hz,1H),7.82–7.65(m,8H),7.60(dd,J＝8.8,3.2Hz,1H),7.44–7.35(m,3H),7.25–7.24(m,3H),7.23–7.18(m,2H),7.13–7.07(m,2H),6.94(d,J＝8.4Hz,2H),3.60(s,3H)；13C NMR(101MHz,CDCl3):δ163.10,158.18,154.94,151.34,145.62,145.14,139.02,135.74,134.24,133.88,131.45,131.29,130.46,129.77,129.55,128.89,128.37,128.28,128.23,127.76,127.68,127.66,126.72,126.63,126.52,126.46,126.17,126.09,125.72,125.68,125.65,125.61,125.07,125.00,124.61,124.42,123.36,121.82,118.08,113.47,113.26,56.29；HRMS(ESI-TOF)m/z Calcd.for C47H31N2O2 +[M+H]+:655.2380；Found:655.2369.
实施例16：
取干燥的100mL Schlenk管中加入(R)-5a(300mg,0.63mmol)，然后在氮气氛下通过注射器加入无水二氯甲烷(10mL)，然后在0℃下向反应体系中滴加BBr3(17％溶解在二氯甲烷,1.9mL,1.90mmol)，在室温下搅拌12小时。反应完全进行后，用冰水淬灭反应并用二氯甲烷(3×15mL)萃取。将合并的有机相用饱和氯化钠洗涤，经Na2SO4干燥后，减压除去溶剂，残余物通过硅胶柱色谱法纯化，使用二氯甲烷/甲醇(100:1)作为洗脱剂，得到白色固体(R)-6a,170mg，收率57％；H NMR(400MHz,CDCl3):δ8.84(dd,J＝4.4,2.0Hz,1H),8.26(br,1H),8.09(dd,J＝8.0,1.6Hz,1H),8.05(d,J＝8.8Hz,1H),7.97(t,J＝8.4Hz,2H),7.79–7.72(m,1H),7.65(d,J＝8.8Hz,1H),7.61(d,J＝8.8Hz,1H),7.57(d,J＝8.8Hz,1H),7.50–7.41(m,3H),7.37–7.31(m,2H),7.31–7.25(m,3H),7.01(d,J＝8.4Hz,1H),6.97(d,J＝8.8Hz,1H)；13C NMR(101MHz,CDCl3):δ163.04,153.21,151.04,149.72,144.63,143.83,139.92,136.04,134.34,134.12,131.99,130.79,129.56,129.13,129.07,128.23,127.92,127.13,126.40,125.25,126.19,125.94,125.80,125.30,124.99,124.52,123.27,122.99,122.13,120.59,116.78,113.77；HRMS(ESI-TOF)m/z Calcd.for C32H21N2O2 +[M+H]+:465.1598；Found:465.1597.
实施例17：
制备方法与实施例16相同，白色固体，119mg,收率62％；1H NMR(400MHz,CDCl3):δ8.17(dd,J＝8.4,1.2Hz,1H),8.10–7.94(m,3H),7.79–7.76(m,2H),7.75(d,J＝4.0Hz,1H),7.70–7.64(m,1H),7.63(d,J＝2.0Hz,1H),7.59(d,J＝8.8Hz,1H),7.57–7.53(m,1H),7.49(ddd,J＝8.0,5.6,2.4Hz,1H),7.43(dd,J＝8.8,6.4Hz,1H),7.36–7.32(m,1H),7.31–7.26(m,2H),7.01(dd,J＝8.8,6.0Hz,2H)；13C NMR(101MHz,CDCl3):δ163.30,153.05,151.05,150.95,144.52,142.83,139.94,138.62,134.17,134.14,132.07,131.05,129.64,129.00,128.24,127.94,127.70,127.18,126.45,126.32,126.16,125.87,125.73,125.55,124.95,124.26,123.82,123.25,121.94,120.07,115.93,114.37；HRMS(ESI-TOF)m/z Calcd.forC32H20ClN2O2 +[M+H]+:499.1208；Found:499.1216.
实施例18：
制备方法与实施例16相同，白色固体，65mg,收率67％；1H NMR(400MHz,CDCl3):δ8.13(d,J＝8.8Hz,1H),8.09(s,1H),8.06(d,J＝4.0Hz,2H),8.00(d,J＝8.4Hz,1H),7.93(d,J＝8.4Hz,1H),7.80–7.73(m,1H),7.71–7.60(m,4H),7.55(dd,J＝10.8,8.8Hz,2H),7.46(d,J＝8.8Hz,1H),7.42(d,J＝6.8Hz,1H),7.36(d,J＝8.4Hz,1H),7.30–7.23(m,3H),7.17(t,J＝7.2Hz,1H),7.04(d,J＝8.8Hz,1H),6.90(d,J＝9.2Hz,1H),6.85(t,J＝7.6Hz,2H)；13C NMR(101MHz,CDCl3):δ163.35,155.61,153.26,151.50,144.17,143.69,140.11,138.16,136.62,134.37,134.31,132.25,131.11,129.59,129.35,128.98,128.57,128.36,127.95,127.09,126.88,126.61,126.49,126.36,125.88,125.31,124.84,124.22,123.26,122.49,120.23,119.45,115.90,113.05；HRMS(ESI-TOF)m/z Calcd.for C38H25N2O2 +[M+H]+:541.1911；Found:541.1915.
实施例19：
制备方法与实施例16相同，白色固体，110mg,收率56％；1H NMR(400MHz,CDCl3):δ8.14(d,J＝8.8Hz,1H),8.11(d,J＝9.2Hz,1H),8.05(s,1H),8.04(d,J＝8.4Hz,1H),7.98(d,J＝8.4Hz,2H),7.76(dd,J＝7.6,1.2Hz,1H),7.65(d,J＝9.2Hz,1H),7.61(s,2H),7.55–7.45(m,4H),7.33–7.25(m,3H),7.20(d,J＝7.6Hz,1H),7.04(d,J＝8.4Hz,1H),6.94(d,J＝8.8Hz,1H),6.84(s,1H),1.92(s,6H)；13C NMR(101MHz,CDCl3):δ163.18,156.54,153.31,151.05,144.41,144.03,140.29,138.61,138.16,136.58,134.36,134.23,132.07,131.01,130.92,129.48,129.03,128.38,128.06,127.92,127.12,126.41,126.30,125.96,125.85,125.62,125.35,125.14,125.02,124.47,123.24,122.38,120.59,120.13,116.41,113.45,21.25；HRMS(ESI-TOF)m/z Calcd.for C40H29N2O2 +[M+H]+:569.2224；Found:569.2222.
实施例20：
制备方法与实施例16相同，白色固体，110mg,收率55％.1H NMR(400MHz,CDCl3):δ8.27(s,1H),8.21(d,J＝8.0Hz,1H),7.88(d,J＝8.8Hz,1H),7.81(d,J＝8.4Hz,2H),7.77–7.65(m,4H),7.64–7.55(m,4H),7.52(d,J＝8.4Hz,1H),7.35(d,J＝8.8Hz,1H),7.31–7.23(m,2H),7.22–7.10(m,4H),7.08(d,J＝7.2Hz,1H),7.04(d,J＝6.8Hz,1H),6.98(t,J＝7.2Hz,1H),6.91(d,J＝8.4Hz,1H),6.84(dd,J＝8.4,5.2Hz,2H)；13C NMR(101MHz,CDCl3):δ163.11,157.67,153.09,151.45,144.85,144.11,139.80,135.71,134.80,134.15,133.86,131.51,131.30,131.23,130.40,130.02,129.95,129.45,128.73,128.29,128.21,127.93,127.87,127.75,127.17,126.49,126.42,126.24,126.21,126.11,125.72,125.64,125.53,125.22,125.14,124.90,124.85,124.35,124.26,122.95,122.04,119.62,115.17,113.70；HRMS(ESI-TOF)m/z Calcd.for C46H29N2O2 +[M+H]+:641.2224；Found:641.2215.(图8，图9)
实施例21：
向干燥的Schlenk烧瓶中加入化合物(R)-6e(96.1mg,0.15mmol)，然后用注射器加入无水二氯甲烷,之后加入氢化钠(12mg,0.3mmol,60％矿物油分散体)。然后在0℃下向溶液中滴加SiiPr3Cl(78μL,0.3mmol)，反应混合物在室温下搅拌1h。反应完全进行后，用冰水淬灭反应并用二氯甲烷(3×15mL)萃取。将合并的有机层用饱和食盐水洗涤，Na2SO4干燥后，减压除去溶剂，残余物通过硅胶柱色谱法纯化，使用石油醚/乙酸乙酯(15:1)作为洗脱剂，得到白色固体(R)-7a,121.3mg，收率92％。1H NMR(400MHz,CDCl3):δ8.53(s,1H),8.33(d,J＝8.0Hz,1H),8.03(dd,J＝22.4,8.4Hz,2H),7.89-7.70(m,8H),7.63(dd,J＝8.8,2.0Hz,2H),7.59(d,J＝8.0Hz,1H),7.46(t,J＝7.4Hz,1H),7.42-7.38(m,1H),7.31(t,J＝7.4Hz,2H),7.27-7.21(m,3H),7.16(d,J＝8.8Hz,1H),6.95(t,J＝7.2Hz,1H),6.84(d,J＝8.4Hz,1H),6.80(t,J＝7.6Hz,1H),6.62(t,J＝7.2Hz,1H),1.02(dt,J＝14.8,7.6Hz,3H),0.75(dd,J＝16.8,7.6Hz,18H)；13C NMR(101MHz,CDCl3):δ163.09,157.78,151.67,151.46,145.60,144.96,138.84,135.63,135.57,134.21,134.19,131.56,131.49,131.41,130.46,130.36,129.14,129.07,128.64,128.55,128.11,128.06,127.84,127.61,127.21,126.83,126.69,126.53,126.40,126.26,126.17,125.91,125.65,125.60,125.57,125.38,125.22,124.98,124.96,124.68,124.16,123.05,122.39,120.12,119.98,113.97,17.86,17.83,12.90；HRMS(ESI-TOF)m/z Calcd.for C55H49N2O2Si+[M+H]+:797.3558；Found:797.3560.
实施例22：
制备方法与实施例21相同，黄色固体，124.6mg,收率66％；1H NMR(400MHz,CDCl3):δ8.49(s,1H),8.29(d,J＝8.4Hz,1H),7.99(dd,J＝17.4,8.4Hz,2H),7.89(d,J＝8.8Hz,1H),7.77-7.62(m,10H),7.43-7.36(m,2H),7.32-7.20(m,5H),7.10(d,J＝8.8Hz,1H),7.00(t,J＝7.2Hz,1H),6.93-6.88(m,2H),6.75(t,J＝7.2Hz,1H),0.55(t,J＝7.4Hz,9H),0.46-0.32(m,6H)；13C NMR(101MHz,CDCl3):δ163.16,158.01,151.53,151.35,145.65,145.03,138.92,135.77,135.65,134.19,134.17,131.49,131.44,131.30,130.45,130.39,129.28,129.25,128.98,128.47,128.15,128.08,127.70,127.40,126.73,126.66,126.53,126.30,126.16,126.14,126.10,125.68,125.61,125.15,125.02,125.00,124.82,124.31,123.31,122.10,120.63,120.55,113.82,6.41,5.27；HRMS(ESI-TOF)m/zCalcd.for C52H43N2O2Si+[M+H]+:755.3088；Found:755.3077.
实施例23：
制备方法与实施例21相同，黄色固体,108.2mg,收率86％；1H NMR(400MHz,CDCl3):δ8.53(s,1H),8.34(d,J＝8.4Hz,1H),8.03(dd,J＝18.6,8.6Hz,2H),7.91(d,J＝8.8Hz,1H),7.81-7.72(m,6H),7.68-7.62(m,4H),7.47-7.38(m,2H),7.35-7.27(m,2H),7.24-7.22(m,3H),7.14(d,J＝8.8Hz,1H),7.01(t,J＝7.4Hz,1H),6.93(d,J＝8.8Hz,1H),6.89(d,J＝8.0Hz,1H),6.73(t,J＝7.6Hz,1H),0.47(s,9H),0.04(s,3H),-0.29(s,3H)；13CNMR(101MHz,CDCl3):δ163.12,157.94,151.64,151.35,145.65,145.03,138.90,135.70,135.64,134.25,134.16,131.52,131.46,131.33,130.47,130.38,129.26,129.22,129.01,128.52,128.16,128.12,127.78,127.68,127.36,126.80,126.68,126.54,126.35,126.23,126.19,126.11,125.70,125.67,125.61,125.56,125.19,125.00,124.80,124.79,124.30,123.38,122.27,121.01,120.60,114.02,25.24,17.75,-3.96,-4.58；HRMS(ESI-TOF)m/zCalcd.for C52H43N2O2Si+[M+H]+:755.3088；Found:755.3089.
实施例24：
制备方法与实施例21相同，黄色固体，121.3mg,收率92％；1H NMR(400MHz,CDCl3):δ8.56(s,1H),8.34(d,J＝8.4Hz,1H),8.06(dd,J＝23.2,8.4Hz,2H),7.89(d,J＝8.4Hz,1H),7.85-7.78(m,5H),7.72(dd,J＝8.6,1.2Hz,2H),7.66-7.60(m,5H),7.55(d,J＝8.0Hz,1H),7.49-7.42(m,4H),7.38-7.33(m,5H),7.30-7.25(m,4H),7.11(t,J＝7.4Hz,1H),7.03-6.93(m,3H),6.81-6.77(m,2H),0.50(s,9H)；13C NMR(101MHz,CDCl3):δ163.20,158.06,151.43,150.80,145.70,145.22,139.18,135.78,135.70,135.55,135.51,134.38,134.07,132.78,132.73,131.52,131.48,130.46,130.40,129.92,129.84,129.41,128.91,128.80,128.49,128.19,128.16,127.81,127.77,127.40,126.81,126.69,126.61,126.35,126.16,126.07,125.74,125.66,125.60,125.33,125.22,125.07,125.02,124.34,123.35,122.25,120.21,120.17,113.52,25.86,18.97；HRMS(ESI-TOF)m/z Calcd.forC62H47N2O2Si+[M+H]+:879.3401；Found:879.3400.
实施例25：
将化合物8a-a(185.8mg,0.65mmol)加入到50mL圆底烧瓶中，加入干燥的N,N-二甲基甲酰胺(4mL)，然后将反应瓶置于冰水浴中，分批缓慢加入NaH(28mg,0.71mmol)，冰水浴搅拌2h。然后缓慢加入化合物8b(200mg,0.71mmol)的N,N-二甲基甲酰胺溶液(4mL)，恢复至室温，搅拌16h。反应液中加入水(10mL)淬灭，二氯甲烷(30mL×3)萃取，有机相再用水(15mL×5)、饱和氯化钠溶液洗涤，分液，有机相用无水硫酸钠干燥，减压浓缩，柱层析(石油醚/乙酸乙酯＝4:1)得到(R)-9a，淡黄色固体，218mg，收率69％；1H NMR(400MHz,CDCl3)δ8.22(d,J＝8.8Hz,1H),8.12(d,J＝8.4Hz,1H),7.94-7.85(m,4H),7.68(dd,J＝6.0,1.6Hz,1H),7.52(d,J＝8.8Hz,1H),7.40-7.35(m,3H),7.33-7.31(m,2H),7.30-7.28(m,2H),7.21(td,J＝8.4,1.6Hz,1H),7.13(d,J＝8.4Hz,1H),5.92(d,J＝14.4Hz,1H),5.83(d,J＝14.4Hz,1H),5.46(s,1H),3.94(s,3H)；13C NMR(101MHz,CDCl3):δ166.02,155.58,151.73,146.91,145.03,137.41,136.69,134.26,134.05,130.78,129.89,129.27,129.01,128.71,128.65,128.26,128.17,127.28,126.99,126.54,125.16,125.12,124.42,123.34,121.04,117.77,117.06,116.86,115.48,67.55,52.97；HRMS(ESI-TOF)m/z Calcd.for C32H23NO4Na+[M+Na]+:508.1519；Found:508.1518。
实施例26：
制备方法与实施例25相同，黄绿色固体，269.2mg，收率55.2％；1H NMR(400MHz,CDCl3)δ8.06(d,J＝8.0Hz,1H),7.99(d,J＝8.0Hz,1H),7.91(s,1H),7.88-7.83(m,2H),7.71(s,1H),7.66(d,J＝8.0Hz,2H),7.50-7.42(m,5H),7.35-7.29(m,3H),7.22(d,J＝8.0Hz,1H),7.16-7.12(m,4H),6.99(d,J＝12.0Hz,2H),6.92(d,J＝8.0Hz,2H),6.90(s,1H),5.74(d,J＝16.0Hz,1H),4.89(d,J＝12.0Hz,1H),3.35(s,3H),1.37(s,9H),1.26(s,9H)；13C NMR(101MHz,CDCl3):δ165.60,156.06,150.15,150.07,149.04,145.85,145.44,137.47,136.71,136.68,135.50,135.33,133.80,133.29,131.67,131.34,130.58,130.52,130.20,129.96,129.31,129.13,129.08,128.89,128.25,128.18,127.96,127.23,126.53,125.37,125.17,124.81,124.16,123.64,123.55,120.49,116.73,71.69,52.24,34.58,34.30,31.41,31.32；HRMS(ESI-TOF)m/z Calcd.for C52H48NO4 +[M+H]+:750.3578；Found:750.3568。
实施例27：
制备方法与实施例25相同，淡黄色固体，280.5mg，收率65.8％；1H NMR(400MHz,CDCl3)δ7.99(d,J＝8.4Hz,1H),7.92(d,J＝8.8Hz,1H),7.86-7.78(m,3H),7.72(s,1H),7.51(d,J＝8.0Hz,2H),7.45-7.38(m,3H),7.32-7.26(m,3H),7.20-7.19(m,2H),7.16-7.09(m,2H),6.99(d,J＝8.0Hz,2H),6.80(d,J＝8.0Hz,2H),6.67(s,1H),5.60(d,J＝12.8Hz,1H),4.97(d,J＝12.8Hz,1H),3.41(s,3H),2.36(s,3H),2.20(s,3H)；13C NMR(101MHz,CDCl3):δ165.69,155.69,149.96,145.99,145.22,137.06,136.75,136.69,136.66,136.20,135.49,135.46,133.78,133.46,131.40,130.76,130.15,130.11,129.99,129.61,129.25,129.13,129.02,128.97,128.25,128.23,128.16,127.99,126.94,126.60,126.56,125.50,125.31,124.89,123.94,123.59,120.49,116.82,71.49,52.36,21.31,21.10；HRMS(ESI-TOF)m/z Calcd.for C46H36NO4 +[M+H]+:666.2639；Found:666.2636。
(图6，图7)
实施例28：
将(R)-9a(200mg，0.4mmol)加入到25mL反应瓶中，加入甲醇(5mL)，滴加2.3mol/L的氢氧化钾溶液(2mmol)，室温搅拌3h，至TLC反应完全，滴加1.0mol/L的稀盐酸溶液(pH≈4)，减压浓缩，二氯甲烷(20mL×3)萃取，合并有机相，然后用饱和氯化钠溶液洗涤，分液，有机相用无水硫酸钠干燥，减压浓缩得到橙黄色固体(R)-10a，160mg，收率85％；1H NMR(400MHz,CDCl3)δ8.28(d,J＝8.0Hz,1H),8.19(d,J＝8.0Hz,1H),8.07-8.04(m,1H),7.91(d,J＝12.0Hz,1H),7.81(d,J＝8.0Hz,1H),7.77(d,J＝8.0Hz,1H),7.72-7.70(m,1H),7.63(d,J＝8.0Hz,1H),7.41-7.36(m,3H),7.31-7.28(m,1H),7.24-7.18(m,3H),7.07(td,J＝8.0,4.0Hz,1H),6.88(d,J＝8.0Hz,1H),5.81(d,J＝12.0Hz,1H),5.73(d,J＝12.0Hz,1H)；13C NMR(101MHz,CDCl3):δ163.98,154.79,151.33,143.23,139.03,135.10,134.07,133.65,131.13,130.04,129.85,129.69,129.61,129.12,128.92,128.77,128.23,128.06,127.56,127.42,126.42,125.22,124.76,124.64,123.20,119.16,117.68,117.44,116.61,114.96,67.94；HRMS(ESI-TOF)m/z Calcd.for C31H22NO4 +[M+H]+:472.1543；Found:472.1552。
实施例29：
制备方法与实施例28相同，淡黄色固体，231.2mg，收率87.3％；1H NMR(400MHz,CDCl3)δ8.15(d,J＝8.0Hz,1H),8.08-8.06(m,2H),7.97(d,J＝12.0Hz,1H),7.78(s,1H),7.73-7.71(m,1H),7.68-7.65(m,2H),7.57-7.54(m,3H),7.51-7.45(m,3H),7.43-7.40(m,2H),7.36-7.28(m,3H),7.25-7.15(m,3H),7.10(d,J＝8.0Hz,1H),5.15(s,2H),1.40(s,9H),1.35(s,9H)；13C NMR(101MHz,CDCl3):δ164.02,154.58,150.69,150.51,149.05,144.40,142.77,138.69,135.68,135.61,135.55,134.58,133.38,133.30,131.50,131.36,130.18,129.85,129.47,129.23,129.19,129.17,128.92,128.66,128.32,128.07,126.92,126.84,126.66,125.71,125.68,125.53,125.25,124.76,123.67,123.24,118.65,116.41,70.89,34.67,34.60,31.41；HRMS(ESI-TOF)m/z Calcd.for C51H46NO4 +[M+H]+:736.3421；Found:736.3428。
实施例30:
制备方法与实施例28相同，淡黄色固体，80mg，收率54.4％；1H NMR(400MHz,CDCl3)δ15.71(s,1H),8.63(dd,J＝6.0,1.6Hz,1H),8.10(s,1H),7.97(d,J＝8.4Hz,1H),7.86(dd,J＝6.8,1.6Hz,1H),7.81(d,J＝8.8Hz,1H),7.74-7.70(m,3H),7.61(d,J＝8.4Hz,1H),7.58-7.56(m,1H),7.55-7.54(m,1H),7.52(t,J＝2.0Hz,1H),7.50-7.46(m,5H),7.32-7.29(m,2H),7.19-7.07(m,3H),6.81(d,J＝8.4Hz,1H),5.42(s,1H),4.80(d,J＝14.0Hz,1H),4.61(d,J＝13.6Hz,1H),1.39(s,9H),1.36(s,9H)；13C NMR(101MHz,CDCl3):δ167.09,157.39,154.11,150.87,148.97,143.73,137.94,135.35,135.04,134.91,134.39,133.22,133.13,132.60,131.64,130.14,129.89,129.17,129.03,128.78,128.61,128.36,127.63,127.05,127.02,126.79,126.63,126.02,125.72,125.68,125.55,124.71,124.50,124.23,123.80,123.64,119.71,116.06,75.23,34.67,34.65,31.39；HRMS(ESI-TOF)m/zCalcd.for C51H46NO4 +[M+H]+:736.3421；Found:736.3425。(图4，图5)
实施例31:含配位单元的联萘轴手性配体在不对称催化合成BINOL、BINAM衍生物、NOBIN衍生物反应中的应用。
选取25mL的Schlenk瓶，加入底物13a(0.2mmol)，碘化亚铜(5mol％)，配体(R)-3a(10mol％)以及碳酸铯(13.75mol％)，用橡胶塞固定瓶口后置换气体(氧气氛围)，然后加入2mL的甲苯溶剂，瓶口上端插一个氧气球于20摄氏度下搅拌72小时，待反应结束，将反应液直接进行硅胶色谱柱纯化，高效液相色谱分析产物的对映体过量值，所得的各取代基联萘酚的实验结果见表1。
表1.2-萘酚的不对称氧化偶联构建手性联萘酚化合物
实施例42：
选取干燥的10mL反应管，加入偶氮底物15a(0.1mmol)，底物15b(0.12mmol),六氟磷酸四乙腈铜(10mol％)，配体(R)-6e(12mol％),1,2-二氯苯，用含有聚四氟垫片的旋塞封住后放入30度的反应盘中搅拌60小时，待反应结束，将反应液直接进行硅胶色谱柱纯化，高效液相色谱分析产物的对映体过量值，所得的各取代基联萘胺衍生物的实验结果见表2。
表2.偶氮羧酸酯导向的不对称氧化还原中性偶联反应构建手性联萘胺衍生物
实施例63：
在干燥的25mL的Schlenk管中，加入2-萘偶氮甲酸苄酯15a(0.1mmol)和2-萘酚衍13a(0.12mmol)，再加入乙酰丙酮酸铜(10mol％)和配体(R)-7a(12mol％)，将反应体系置换氮气三次，然后用注射器加入2mL间二甲苯作溶剂，室温下反应12小时。待反应进行完后，将反应液直接进行硅胶色谱柱纯化，高效液相色谱分析产物的对映体过量值，所得的各取代基联萘酚胺衍生物的实验结果见表3。
表3.偶氮羧酸酯导向的不对称氧化还原中性偶联反应构建手性联萘酚胺衍生物
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何属于本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到的变化或者替换，都应涵盖在本发明的保护范围之内，因此，本发明的保护范围应该以权力要去的保护范围为准。
Claims (10)
1.一种含配位单元的联萘轴手性配体，其特征在于，所述联萘轴手性配体如下述通式(Ⅰ)所示：
在所述通式(Ⅰ)中：
用﹡标注的轴手性为R构型或者S构型；
R1选自羟基、甲基硅基氧基、乙基硅基氧基、正丙基硅基氧基、异丙基硅基氧基、正丁基硅基氧基、异丁基硅基氧基、正戊基硅基氧基、异戊基硅基氧基、新戊基硅基氧基、苯基硅基氧基、甲基取代的苯基硅基氧基、三氟甲基取代的苯基硅基氧基、甲氧基取代的苯基硅基氧基、叔丁基取代的苯基硅基氧基或氟取代的苯基硅基氧基中的任一种；
R2和R3为氢、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、三氟甲基取代的苯基、甲氧基取代的苯基、乙氧基取代的苯基、叔丁基氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基或碘取代的苯基中的任一种；
所述配位单元A选自通式1a或者通式1d中的任一种：所述通式1a和通式1d如下所示：
R4为羟基、甲基氧基、乙基氧基、正丙基氧基、异丙基氧基、正丁基氧基、异丁基氧基、正戊基氧基、异戊基氧基、新戊基氧基或苄氧基中的任一种；
R7为卤素、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、三氟甲基取代的苯基、甲氧基取代的苯基、乙氧基取代的苯基、叔丁基氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基、碘取代的苯基或者蒽基中的任一种。
2.一种如权利要求1中任一所述含配位单元的联萘轴手性配体的制备方法，其特征在于，所述联萘轴手性配体的配位单元分别为通式1a以及通式1d时，制备方法如下：
(1)配位单元为通式1a的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物b溶解在有机溶剂中，在碱的作用下反应1-48小时，即可；
(2)配位单元为通式1d的联萘轴手性配体的制备：结构式为a的联萘轴手性化合物与化合物e在氮气或者惰性气体保护下溶解在有机溶剂中，在铜盐、碱、草酰胺配体的作用下0-150℃反应1-60小时，即可；
所述化合物b和化合物e中的Y分别独立选自氯原子、溴原子或碘原子。
3.根据权利要求2所述的含配位单元的联萘轴手性配体的制备方法，其特征在于，所述有机溶剂为甲醇、乙醇、异丙醇、正丁醇、丙酮、二氯甲烷、三氯甲烷、四氯化碳、1,1-二氯乙烷、1,2-二氯乙烷、乙醚、甲基叔丁基醚、四氢呋喃、1,4-二氧六环、苯、甲苯、二甲苯、乙腈、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮以及二甲基亚砜中的一种或几种；
所述惰性气体包括氩气、氦气、氖气以及氪气中的一种或几种；
所述铜盐为氯化铜、溴化铜、乙酰丙酮铜、氯化亚铜、溴化亚铜、碘化亚铜、六氟磷酸四乙腈铜中的一种或几种；
所述碱选自无机碱氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、碳酸铯、磷酸钾、磷酸钠、甲醇钠、叔丁醇钾、叔丁醇钠、氢化钠、氢化钙、有机碱正丁基锂、仲丁基锂、叔丁基锂、二异丙基氨基锂、1,8-二氮杂双环[5.4.0]十一碳-7-烯、三乙胺以及吡啶中的一种；
所述联萘轴手性配体的制备方法中，制备配位单元为通式1a的联萘轴手性配体时，化合物a与化合物b的投料比为摩尔比1:5～5:1；
所述联萘轴手性配体的制备方法中，制备配位单元为通式1d的联萘轴手性配体时，化合物a与化合物e的投料比为摩尔比1:3～3:1；
所述配位单元为通式1d的联萘轴手性配体的制备方法中，所述配体为草酰胺配体。
4.一种络合物，其特征在于，所述络合物由如权利要求1中所述的任一含配位单元的联萘轴手性配体和过渡金属化合物组合形成，所述过渡金属化合物选自碘化亚铜、溴化亚铜、氯化亚铜、乙酰丙酮铜、六氟磷酸四乙腈铜中的至少一种。
5.一种合成联萘酚化合物的方法，其特征在于，所述合成联萘酚化合物的方法包括以下步骤：
在反应气体下，将如权利要求1所述的配位单元为1a的联萘轴手性配体，其中R1为羟基、R2、R3为对叔丁基苯基、R4为羟基，与铜盐和碱在有机溶剂中络合，在所需反应温度下，经所需反应时间将化合物5进行如下式反应得到化合物6，
其中，R8为氢、甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基、环己基、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基或卤素；
用*标注的手性轴为S构型或R构型。
6.一种合成联萘胺衍生化合物的方法，其特征在于，所述合成联萘胺衍生化合物的方法包括以下步骤：
在有机溶剂中，将如权利要求1所述的配位单元为1d的联萘轴手性配体，其中配位单元中R1为羟基、R7为蒽基，与铜盐络合，在所需反应温度下，经所需反应时间将化合物7与化合物8进行如式反应得到化
其中，R9选自甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基、环己基、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基；R12选自苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基；R10-R11以及R13-R14分别独立为氢、甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基、环己基、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、酯基或卤素；
用*标注的手性轴为S构型或R构型。
7.一种合成联萘酚胺衍生物化合物的方法，其特征在于，包括如下步骤：
在有机溶剂中，将如权利要求1所述的配位单元为1d的联萘轴手性配体，其中配位单元中R1为三异丙基硅基氧基、R7为蒽基，与铜盐络合，在所需反应温度下，经所需反应时间将化合物10与化合物11进行如式反应得到化合物12，
其中，R15选自甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基、环己基、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基；R16-R20分别独立为氢、甲基、乙基、异丙基、正丁基、异丁基、叔丁基、环戊基、环己基、苯基、甲基取代的苯基、乙基取代的苯基、异丙基取代的苯基、叔丁基取代的苯基、新戊基取代的苯基、金刚基取代的苯基、酯基或卤素。
8.根据权利要求5所述的合成联萘酚化合物的方法，其特征在于，所述反应气体为氧气、一氧化碳、二氧化碳、空气中的一种或几种；
所述有机溶剂为二氯甲烷、三氯甲烷、1,1-二氯乙烷、1,2-二氯乙烷、四氢呋喃、1,4-二氧六环、苯、甲苯、二甲苯中的一种或几种；
所述铜盐选自氯化亚铜、溴化亚铜、碘化亚铜、乙酰丙酮铜、六氟磷酸根四乙腈铜中的至少一种；
所述碱选自无机碱氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、磷酸钾、磷酸钠、碳酸铯、甲醇钠、叔丁醇钾、叔丁醇钠、氢化钠、氢化钙或有机碱正丁基锂、仲丁基锂、叔丁基锂、二异丙基氨基锂、1,8-二氮杂双环[5.4.0]十一碳-7-烯、三乙胺以及吡啶中的至少一种；
所述化合物5在所述有机溶剂中的摩尔浓度为0.01～1.0M；
所述铜盐与碱的摩尔比为1:1～1:10；
所述铜盐与配位单元为1a的联萘轴手性配体的摩尔比为1:1～1:5；
所述的反应温度为-30～50℃；
所述的反应时间为1～72小时。
9.根据权利要求6所述的合成联萘胺衍生化合物的方法，其特征在于，所述有机溶剂为甲醇、乙醇、异丙醇、二氯甲烷、三氯甲烷、四氯化碳、1,1-二氯乙烷、1,2-二氯乙烷、乙醚、甲基叔丁基醚、1,4-二氧六环、苯、甲苯、二甲苯和1,2-二氯苯中的一种或几种；
所述铜盐选自氯化亚铜、溴化亚铜、碘化亚铜、乙酰丙酮铜以及六氟磷酸根四乙腈铜中的至少一种；
所述化合物7和化合物8在所述有机溶剂中的摩尔浓度为0.01～1.0M；
所述铜盐与配位单元为1d的联萘轴手性配体的摩尔比为1:1～1:5；
所述化合物7与铜盐的摩尔比为1:0.01～1:0.5；
所述的反应温度为-30～50℃；
所述的反应时间为1～72小时。
10.根据权利要求7所述的合成联萘酚胺衍生化合物的方法，其特征在于，所述有机溶剂为二氯甲烷、三氯甲烷、四氯化碳、1,1-二氯乙烷、1,2-二氯乙烷、乙醚、甲基叔丁基醚、苯、甲苯以及二甲苯中的一种或几种；
所述铜盐选自氯化亚铜、溴化亚铜、碘化亚铜、醋酸铜、乙酰丙酮铜和六氟磷酸根四乙腈铜的至少一种；
所述化合物10和化合物11在所述有机溶剂中的摩尔浓度为0.01～1.0M；
所述铜盐与配位单元为1d的联萘轴手性配体的摩尔比为1:1～1:5；
所述化合物10与铜盐的摩尔比为1:0.01～1:0.5；
所述的反应温度为-30～50℃；
所述的反应时间为1～72小时。
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