CN101508702A - 四氢喹啉和吲哚啉衍生的磷氮配体、合成方法和应用 - Google Patents
四氢喹啉和吲哚啉衍生的磷氮配体、合成方法和应用 Download PDFInfo
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- CN101508702A CN101508702A CNA2009100484386A CN200910048438A CN101508702A CN 101508702 A CN101508702 A CN 101508702A CN A2009100484386 A CNA2009100484386 A CN A2009100484386A CN 200910048438 A CN200910048438 A CN 200910048438A CN 101508702 A CN101508702 A CN 101508702A
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- Prior art keywords
- compound
- dinaphthalene
- tetrahydroquinoline
- indoline
- alkali
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- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000003446 ligand Substances 0.000 title claims description 3
- YUWBVKYVJWNVLE-UHFFFAOYSA-N [N].[P] Chemical compound [N].[P] YUWBVKYVJWNVLE-UHFFFAOYSA-N 0.000 title abstract description 30
- 230000015572 biosynthetic process Effects 0.000 title description 4
- 238000003786 synthesis reaction Methods 0.000 title description 3
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 239000003513 alkali Substances 0.000 claims abstract description 15
- 229910052751 metal Inorganic materials 0.000 claims abstract description 13
- 239000002184 metal Substances 0.000 claims abstract description 13
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims abstract description 11
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- 150000001875 compounds Chemical class 0.000 claims description 47
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical group OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 claims description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 230000003197 catalytic effect Effects 0.000 claims description 10
- 239000003921 oil Substances 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 5
- 230000000996 additive effect Effects 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- 238000004809 thin layer chromatography Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 229940093916 potassium phosphate Drugs 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000002475 indoles Chemical class 0.000 claims description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002808 molecular sieve Substances 0.000 claims description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 2
- 235000015320 potassium carbonate Nutrition 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 abstract description 7
- 239000000758 substrate Substances 0.000 abstract description 6
- 229910017464 nitrogen compound Inorganic materials 0.000 abstract description 4
- 239000000047 product Substances 0.000 abstract description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 2
- -1 chiral binaphthol compound Chemical class 0.000 abstract description 2
- 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 2
- 238000001308 synthesis method Methods 0.000 abstract 2
- 125000000746 allylic group Chemical group 0.000 abstract 1
- 239000012264 purified product Substances 0.000 abstract 1
- 238000001819 mass spectrum Methods 0.000 description 30
- QRWRJDVVXAXGBT-UHFFFAOYSA-N 2-Methylindoline Chemical compound C1=CC=C2NC(C)CC2=C1 QRWRJDVVXAXGBT-UHFFFAOYSA-N 0.000 description 12
- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000004679 31P NMR spectroscopy Methods 0.000 description 4
- 241000790917 Dioxys <bee> Species 0.000 description 4
- 235000010290 biphenyl Nutrition 0.000 description 4
- 239000004305 biphenyl Substances 0.000 description 4
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 239000012454 non-polar solvent Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 241000522254 Cassia Species 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000002476 indolines Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657154—Cyclic esteramides of oxyacids of phosphorus
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- B01J2231/44—Allylic alkylation, amination, alkoxylation or analogues
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/827—Iridium
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种基于联萘二酚骨架的磷氮类化合物、合成方法,是一种有效的以手性联萘二酚类化合物、三氯化磷和手性四氢喹啉和吲哚啉为原料,在碱的作用下合成光学纯的磷氮类化合物的方法。该方法的原料易得、反应条件温和、产物易于分离提纯。本发明所合成的基于联萘二酚骨架的磷氮类化合物,可以有效的应用于金属铱催化的烯丙基取代反应中,能以高的对映选择性和区域选择性得到产物,极大地拓宽了此类反应的底物范围。
Description
技术领域
本发明涉及一种手性联萘二酚骨架的磷氮类化合物、合成方法和应用,该方法可以高收率的合成这种配体,并把该配体成功的应用于3-吲哚-1-丙烯类化合物的不对称合成,该类配体可以应用在各种金属催化的不对称反应中。
背景技术
基于光学纯的联萘二酚骨架的磷氮类化合物广泛的应用于过渡金属催化的形成碳碳键和碳杂键的反应之中,可以高对映选择性、区域选择性的合成目标化合物。其中以Ferringa配体及其衍生物为代表[(a)Feringa,B.L.Acc.Chem.Res.2000,33,346.(b)Minnaard,A.J.;Feringa,B.L.Lefort,L.;de Vries,J.G.;Acc.Chem.Res.2007,40,1267.(c)Alexakis,A.;Rosset,S.;Allamand,J.;March,S.;Guillen,F.;Benhaim,C.Synlett 2001,1375-1378.(d)Naasz,R.;Arnold,L.A.;Minnaard,A.J.;Feringa,B.L.Angew.Chem.Int.Ed.2001,40,927-930.(e)Polet,D.;Alexakis,A.Synthesis 2004,2586-2590.]。这类泡沫状固体的配体不但合成复杂,难以通过重结晶提纯,并且金属催化的不对称反应中还存在一些局限性。例如,在金属铱催化的烯丙基取代反应中,对邻位带有取代基的肉桂碳酸酯类底物,收率和对映选择性都有明显的降低[(a)López,F.;Ohmura,T.;Hartwig,J.F.J.Am.Chem.Soc.2003,125,3426.(b)Polet,D.;Alexakis,A.;Tissot-Croset,K.;Corminboeuf,C.;Ditrich,K.Chem.Eur.J.2006,12,3596.(c)Yamashita,Y.;Gopalarathnam,A.;Hartwig,J.F.J.Am.Chem.Soc.2007,129,7508.(d)Pouy,M.J.;Leitner,A.;Weix,D.J.;Ueno,S.;Hartwig,J.F.Org.Lett.2007,9,3949.(e)Liu,W.-B.;He,H.;Dai,L.-X.;You,S.-L.Org.Lett.2008,10,1815.]。为了解决这些问题,我们设计合成了一系列基于联萘二酚骨架的磷氮类化合物,该配体合成简单,容易通过重结晶提纯,并且对金属铱催化的烯丙基取代反应具有非常好的效果,可以有效解决邻位取代的肉桂碳酸酯底物的对映选择性问题。因此该配体对于金属铱催化的烯丙基取代反应底物范围的拓展具有非常重要的意义,可以潜在应用于各种金属催化的不对称反应。
发明内容
本发明的目的是提供一种有效的合成光学纯的磷氮类化合物、合成方法和这种化合物在金属铱催化的烯丙基取代反应中的应用。
本发明的方法是一种有效的用联萘二酚、三氯化磷和四氢喹啉和吲哚啉类化合物合成磷氮类化合物的方法。
本发明的方法是一种有效的以光学纯的联萘二酚,三氯化磷,光学纯的四氢喹啉和吲哚啉类化合物为原料的合成基于联萘二酚骨架的磷氮类化合物的方法。
本发明所合成的光学纯的磷氮类化合物可以应用在金属铱催化的不对称烯丙基取代反应中,能以高的效率和对映选择性得到产物。
本发明的方法所述的合成手性联萘二酚骨架的磷氮类化合物的结构式是:
其中联萘骨架具有轴手性结构,*为手性碳原子;R1、R2任意选自卤素、C1-C16的烷基、C3-C16的环烷基;C4-C10的含N、O或S的杂环基或者杂芳基、芳基、R取代的芳基;所述的芳基是苯基或萘基;R为C1-C4的烷基、C1-C4的全氟烷基、卤素或C1-C4的烷氧基;n的值为0或1。
本发明的手性联萘二酚骨架的磷氮类化合物是以联萘二酚、三氯化磷和四氢喹啉和吲哚啉类化合物为原料,在有机溶剂和碱的作用下反应制得,可用下式表示:
其中联萘二酚为光学纯的轴手性化合物,*表示手性碳原子,n为0或1,base为前述提到的各种碱及碱和添加剂的组合,solv.为前文提到的各种溶剂。联萘二酚类化合物结构式为:四氢喹啉和吲哚啉类化合物结构式为:其中R1、R2任意选自C1-C16的烷基或C3-C16的环烷基;C4-C10的含N、O或S的杂环基或者杂芳基、芳基或R取代的芳基;所述的芳基是苯基或萘基;R为C1-C4的烷基、C1-C4的全氟烷基、卤素或C1-C4的烷氧基;n为0或1,*为手性碳原子。
所述的碱是三乙胺、1,8-二氮杂二环[5,4,0]十一碳-7-烯、1,5-二氮杂二环[4,3,0]壬-5-烯、N,O-双(三甲基硅基)乙酰胺、碳酸铯、碳酸钾、磷酸钾、醋酸钾、磷酸钾、氢化钠、正丁基锂、二(三甲基硅基)氨基钠、二(三甲基硅基)氨基锂、二(三甲基硅基)氨基钾、甲醇钠、质子海绵、叔丁醇钾、叔丁醇钠或者二异丙基乙基胺,或者是上述的碱和三氟磺酸银、氯化锂或分子筛等添加剂的组合。其中碱和添加物的重量比为1∶0.1-5。
所述的联萘二酚类化合物、四氢喹啉和吲哚啉类化合物、三氯化磷、碱的摩尔比为1-1.5:1-1.5:1-1.5:3-10,推荐反应的摩尔比为:联萘二酚类化合物、四氢喹啉和吲哚啉类化合物、三氯化磷、碱的摩尔比为1:1:1:6。反应在温度为-78℃至120℃,推荐反应温度为:-78℃至80℃。反应时间为8小时—24小时。
本发明方法中,所述水为蒸馏水。所述有机溶剂可以是极性或非极性溶剂。如苯、四氯化碳、石油醚、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二氧六环、乙腈等。
采用本发明方法所得产物联萘二酚磷氮类化合物可以经过重结晶,薄层层析,柱层析减压蒸馏等方法加以分离。如用重结晶的方法,推荐溶剂为极性溶剂与非极性溶剂的混合溶剂。推荐溶剂可为二氯甲烷—正己烷,异丙醇—石油醚,乙酸乙酯—石油醚,乙酸乙酯—正己烷,异丙醇—乙酸乙酯—石油醚等混合溶剂。用薄层层析和柱层析方法,所用的展开剂为极性溶剂与非极性溶剂的混合溶剂。推荐溶剂可为异丙醇—石油醚,乙酸乙酯—石油醚,乙酸乙酯—正己烷,异丙醇—乙酸乙酯—石油醚等混合溶剂,其体积比可以分别是:极性溶剂:非极性溶剂=1:0.1—500。例如:乙酸乙酯:石油醚=1:0.1—50,异丙醇:石油醚=1:0.1—500。
本发明提供了一种有效的由联萘二酚类化合物、四氢喹啉和吲哚啉类化合物和三氯化磷为原料合成基于联萘骨架的磷氮类化合物的方法。该方法反应条件温和,操作简单原料易得,收率高,提纯方便。
本发明涉及到的基于联萘二酚骨架的磷氮类化合物,可以应用在金属铱催化的多种不同类型的吲哚类化合物和烯丙基碳酸酯类化合物的反应中,反应的产率也较好,区域选择性高,对映选择性高。可以有效解决邻位取代的肉桂碳酸酯作为底物的对映选择性问题,拓宽了此类反应的底物范围。
具体实施方式
通过下述实施例将有助于理解本发明,但并不限制本发明的内容。
实施例1:基于手性联萘二酚类磷氮类化合物的合成:
氩气保护下,在一个干燥的250毫升三口瓶中,加入甲苯(toluene)(50mL)和三苯基磷(0.67mL,7.7mmol),冷却至0℃;在另一个干燥的25毫升烧瓶中,加入手性四氢喹啉和吲哚啉衍生物(7.7mmol),甲苯(8mL),和三乙胺(1.8mL,12.9mmol),然后逐渐滴加到上述250毫升的烧瓶中。滴加完毕后,升温至80℃反应6小时,然后再逐渐冷却至-78℃。再向该体系中缓慢加入R或S联萘二酚(bBINOL)(7.0mmol)和三乙胺(3.5mL,25.2mmol)的甲苯(30mL)和四氢呋喃(6mL)溶液。该体系于室温(rt)下搅拌过夜,硅藻土过滤,减压蒸馏除去溶剂,粗产物通过柱层析分离(石油醚/乙酸乙酯/三乙胺:10/1/0.01)。P1:O,O′-[(R)-1,1′-联萘-2,2′-二酚基]-N-[(R)-2-甲基二氢吲哚]磷氮
白色粉末(White powder),熔点:201-204℃;收率(收率):84%,>95%deaccording to 1H NMR),[α]D 20=-315.4°(c 0.5,CHCl3).1H NMR(300MHz,CDCl3)δ=8.01-7.86(m,4H),7.57(d,J=8.7Hz,1H),7.46-7.37(m,4H),7.32-7.23(m,3H),7.13(d,J=6.9Hz,1H),6.94-6.79(m,3H),3.73(m,1H),3.12(dd,J=8.4,15.6Hz,1H),2.38(d,J=15.6Hz,1H),1.06(d,J=6.0Hz,3H).31P NMR(121MHz,CDCl3)δ=147.0.13C NMR(75MHz,CDCl3)δ=149.76,149.70,149.4,145.2,145.0,132.77,132.75,132.60,132.59,131.5,130.9,130.64,130.60,130.5,130.1,128.3,127.05,127.01,126.91,126.22,126.17,125.5,125.0,124.7,124.17,124.10,122.69,122.67,121.78,121.76,121.5,121.06,121.03,112.7,112.5,55.84(d,J=4.6Hz),37.5,23.23(d,J=1.7Hz).质谱(EI,m/z,rel.intensity)447(M+,80);HRMS-EI:m/z[M]+计算值(calcd for)C29H22NO2P(M+):447.1388,实际值(Found):447.1392.IR(KBr):3054,2966,2924,2849,1620,1590,1508,1479,1464,1457,1432,1369,1253,1234,1222,1204,1160,1106,1071,1025,986,950,939,924,823,807,748cm-1.
P2:O,O′-[(S)-1,1′-联萘-2,2′-二酚基]-N-[(R)-2-甲基二氢吲哚]磷氮
白色粉末(White powder),收率:87%;熔点167-171℃;Rf=0.3(石油醚-乙酸乙酯-三乙胺,10:1:0.01);de>95%;[α]D 20=+213.4°(c0.5,CHCl3).1H NMR(300MHz,CDCl3)δ=7.97(d,J=8.7Hz,1H),7.91(d,J=8.1Hz,1H),7.80(d,J=8.1Hz,1H),7.64(d,J=8.4Hz,1H),7.54(d,J=8.4Hz,1H),7.43-7.35(m,4H),7.25(m,2H),7.11(d,J=9.0Hz,1H),7.07(d,J=8.1Hz,1H),6.79-6.71(m,2H),6.62-6.57(m,1H),4.40(m,1H),3.31(dd,J=9.0,15.0Hz,1H),2.50(d,J=15.3Hz,1H),0.80(d,J=6.3Hz,3H).31P NMR(121MHz,CDCl3)δ=149.4.13C NMR(75MHz,CDCl3)δ=150.03,149.95,149.0,145.7,145.5,132.83,132.81,132.50,132.48,131.5,131.08,131.04,130.8,130.4,129.6,128.3,128.2,127.0,126.8,126.7,126.2,126.0,125.0,124.8,124.5,124.3,124.2,122.35,122.32,122.1,121.72,121.70,121.1,113.5,113.4,55.43(d,J=8.8Hz),37.71(d,J=1.7Hz),23.14(d,J=2.9Hz).质谱(EI,m/z,rel.intensity)447(M+,80);HRMS-EI:m/z[M]+计算值(calcd for)C29H22NO2P(M+):447.1388,实际值(Found):447.1386.IR(KBr):3049,2973,2953,2919,1618,1590,1505,1478,1459,1430,1369,1325,1313,1251,1232,1220,1205,1106,1070,1042,1025,982,949,906,819,797,789,755,747cm-1.
P3:O,O′-[(R)-1,1′-联萘-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
白色固体,收率92%;熔点210-212℃;Rf=0.4(石油醚-乙酸乙酯-三乙胺,10:1:0.01);de>95%;[α]D 20=-255.2°(c1.0,CHCl3).1H NMR(300MHz,CDCl3)δ=8.01(d,J=9.0Hz,1H),7.94-7.89(m,3H),7.60(d,J=8.7Hz,1H),7.55(dd,J=3.6,8.1Hz,1H),7.42(dd,J=3.6,8.1Hz,4H),7.31-7.21(m,3H),7.11-7.06(m,2H),6.93(t,J=7.2Hz,1H),3.71(m,1H),2.78(t,J=4.5Hz,2H),2.04-1.92(m,1H),1.45-1.38(m,1H),0.94(d,J=6.6Hz,3H).31P NMR(121MHz,CDCl3)δ=141.0.13C NMR(75MHz,CDCl3)δ=150.0,149.9,149.4,139.9,139.6,132.75,132.73,132.7,131.50,131.48,130.61,130.55,129.9,129.8,128.3,128.2,127.2,127.1,126.38,126.35,126.26,126.20,126.15,126.06,125.0,124.6,124.11,124.03,122.12,122.09,121.8,121.66,121.63,121.31,121.28,119.8,119.3,45.73(d,J=2.3Hz),27.9,22.8,19.0.质谱(EI,m/z,rel.intensity)461(M+,66);HRMS-EI:m/z[M]+计算值(calcd for)C30H24NO2P(M+):461.1545,实际值(Found):461.1548.IR(KBr):3055,2976,2941,1620,1590,1575,1508,1490,1465,1448,1432,1369,1326,1311,1229,1201,1161,1120,1072,1023,987,952,944,940,930,869,861,823,806,786,749cm-1.
P4:O,O′-[(S)-1,1′-联萘-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
白色固体,收率87%;熔点200-202℃;Rf=0.4(石油醚-乙酸乙酯-三乙胺,10:1:0.01);de>95%;[α]D 20=+241.9°(c1.0,CHCl3).1H NMR(300MHz,CDCl3)δ=7.94-7.85(m,4H),7.47-7.18(m,9H),7.08-6.93(m,3H),3.88-3.82(m,1H),2.75(m,2H),1.97-1.85(m,1H),1.49-1.42(m,1H),0.83(d,J=6.6Hz,3H).31P NMR(121MHz,CDCl3)δ=143.8.13C NMR(75MHz,CDCl3)δ=149.54,149.45,149.0,139.8,139.5,132.7,132.5,131.4,130.7,130.4,129.6,128.32,128.25,127.11,127.05,127.0,126.2,126.1,126.0,124.8,124.6,124.05,123.98,122.21,122.16,121.9,121.4,121.1,45.2,28.2,22.2,17.6.质谱(EI,m/z,rel.intensity)461(M+,69);HRMS-EI:m/z[M]+计算值(calcd for)C30H24NO2P(M+):461.1545,实际值(Found):461.1549.IR(KBr):3055,2974,1619,1587,1577,1505,1491,1463,1453,1431,1378,1360,1326,1307,1228,1204,1190,1155,1133,1116,1096,1071,1054,1027,983,944,862,821,799,792,782,748cm-1.
P5:O,O′-[(R)-1,1′-联萘-3,3’-二溴代-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)602(M+).
P6.O,O′-[(S)-1,1′-联萘-3,3’-二溴代-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)602(M+).
P7:O,O′-[(R)-1,1′-联萘-3,3’-二苯基-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)599(M+).
P8:O,O′-[(S)-1,1′-联萘-3,3’-二溴代-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)599(M+).
P9:O,O′-[(R)-1,1′-联萘-3,3’-二异丙基-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)531(M+).
P10:O,O′-[(S)-1,1′-联萘-3,3’-二异丙基-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)531(M+).
P11:O,O′-[(R)-1,1′-(5,6,7,8-四氢联萘)-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)455(M+).
P12:O,O′-[(S)-1,1′-(5,6,7,8-四氢联萘)-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
P13:O,O′-[(R)-1,1′-(5,6-亚甲基二氧基联苯)-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)435(M+).
P14:O,O′-[(S)-1,1′-(5,6-亚甲基二氧基联苯)-2,2′-二酚基]-N-[(R)-2-甲基-吲哚啉]磷氮
质谱(EI,m/z)435(M+).
P15:O,O′-[(R)-1,1′-联萘-3,3’-二溴代-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
质谱(EI,m/z)617(M+).
P16:O,O′-[(S)-1,1′-联萘-3,3’-二溴代-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
质谱(EI,m/z)617(M+).
P17:O,O′-[(R)-1,1′-联萘-3,3’-二苯基-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P18:O,O′-[(S)-1,1′-联萘-3,3’-二苯基-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P19:O,O′-[(R)-1,1′-联萘-3,3’-二异丙基-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P20:O,O′-[(S)-1,1′-联萘-3,3’-二异丙基-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P21:O,O′-[(R)-1,1′-(5,6,7,8-四氢联萘)-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P22:O,O′-[(S)-1,1′-(5,6,7,8-四氢联萘)-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
质谱(EI,m/z)469(M+).
P23:O,O′-[(R)-1,1′-(5,6-亚甲基二氧基联苯)-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
P23:O,O′-[(S)-1,1′-(5,6-亚甲基二氧基联苯)-2,2′-二酚基]-N-[(R)-2-甲基-1,2,3,4-四氢喹啉]磷氮
该化合物的应用实施例2:该磷氮化合物和金属铱形成络合物催化吲哚烯丙基取代反应
在一干燥的反应管中依次加入[Ir(COD)Cl]2(0.004mmol)、L2或者L3(0.008mmol)、正丙胺(0.5mL)和THF(0.5mL),60℃下反应20分钟,然后自然冷至室温后油泵抽干。再依次向反应管中加入吲哚(0.4mmol)、碳酸铯(0.2mmol)、烯丙基碳酸酯(0.2mmol)、dioxane(2mL),加热回流反应。反应结束后,减压除去溶剂后残留物柱层析分离得产物(乙酸乙酯/石油醚=1/100-1/30,v/v)。
P1:3-(1-(4-溴代苯基)烯丙基)-1-氢-吲哚
白色固体,熔点88-90℃,Rf=0.3(正己烷-乙醚,10:1).b/1>99/1,收率:81%,90%ee(重结晶后的ee:>99%)[手性AD-H柱(0.46cm x 25cm);正己烷/异丙醇=90/10;流速=1.0毫升/分钟;检测波长=230nm;tR=10.23(minor),10.92(major)min].[α]D 20=-6.1°(c0.5,CHCl3).1H NMR(300MHz,CDCl3)δ=7.98(brs,1H),7.41-7.33(m,4H),7.20-7.13(m,3H),7.03(t,J=7.5Hz,1H),6.87(d,J=2.1Hz,1H),6.30(ddd,J=7.2,10.2,17.1Hz,1H),5.20(dt,J=1.2,10.2Hz,1H),5.04(dt,J=1.2,17.1Hz,1H),4.91(d,J=7.2Hz,1H).13C NMR(75MHz,CDCl3)δ=142.1,139.8,136.5,131.4,130.2,126.5,122.4,122.2,120.0,119.6,117.8,115.9,111.1,46.3.质谱(EI,m/z,rel.intensity)311(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C17H14NBr(M+):311.0310,实际值(Found):311.0312.IR(KBr):3418,3058,1637,1618,1486,1456,1417,1353,1336,1220,1095,1072,1011,910,766,743cm-1.
P2:3-(1-(4-甲氧基苯基)烯丙基)-2-苯基-1-氢-吲哚
白色固体;熔点148-150℃,Rf=0.3(正己烷-乙酸乙酯,10:1).b/1>99/1;56%收率;83%ee[手性AS-H柱(0.46cm x 25cm);正己烷/异丙醇=90/10;流速=0.6毫升/分钟;检测波长=254nm;tR=15.65(major),17.51(minor)min].[α]D 20=-30.2°(c0.5,CHCl3).1H NMR(300MHz,CDCl3):δ=8.07(s,1H),7.53-7.36(m,7H),7.22(d,J=8.7Hz,2H),7.16(t,J=7.8Hz,1H),6.99(t,J=7.8Hz,1H),6.80(d,J=9.0Hz,2H),6.49(ddd,J=6.9,10.2,17.1Hz,1H),5.20(d,J=9.9Hz,1H),5.07(d,J=8.7Hz,1H),5.06(d,J=16.8Hz,1H),3.76(s,3H).13C NMR(75MHz,CDCl3):δ=157.7,140.3,136.2,125.3,135.2,132.9,129.2,128.7,128.4,127.9,127.8,122.0,121.3,119.4,115.8,113.8,113.5,110.9,55.1,45.0.质谱(EI,m/z,rel.intensity)339(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C24H21NO:339.1623;实际值(Found):339.1621.IR(KBr):3406,3057,2956,2924,2853,1606,1581,1509,1454,1304,1245,1177,1032,916,821,743,764,700cm-1.
P3:3-(1-(2-甲氧基苯基)烯丙基)-1-氢-吲哚
黄色油状液体,Rf=0.3(正己烷-乙酸乙酯,10:1).b/1>99/1;47%收率,90%ee[手性OD-H柱(0.46cm x 25cm);正己烷/异丙醇=98/12;流速=1.0毫升/分钟;检测波长=254nm;tR=27.49(minor),32.31(major)min].[α]D 20=+7.8°(c0.5,CHCl3).1H NMR(300MHz,CDCl3)δ=7.63(br s,1H),7.43(d,J=7.8Hz,1H),7.19-7.08(m,4H),7.00(t,J=7.2Hz,1H),6.87-6.81(m,2H),6.71(d,J=1.2Hz,1H),6.29(ddd,J=6.3,10.2,16.8Hz,1H),5.43(d,J=6.0Hz,1H),5.14(d,J=10.2Hz,1H),4.98(d,J=16.8Hz,1H),3.76(s,3H).13C NMR(75MHz,CDCl3)δ=156.7,140.0,136.4,131.4,129.2,127.3,126.9,122.5,121.7,120.4,119.7,119.0,118.0,115.0,110.9,110.6,55.5,38.7.质谱(EI,m/z,rel.intensity)263(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C18H17NO(M+):263.1310,实际值(Found):263.1319.IR(KBr):3418,3078,3059,3003,2955,2934,2837,1637,1619,1599,1587,1548,1490,1457,1438,1419,1244,1105,1029,917,743cm-1.
P4:3-(1-(2-氯苯基)烯丙基)-1-氢-吲哚
黄色油状液体,Rf=0.2(正己烷-乙醚,10:1).b/1>99/1,55%收率,79%ee[手性OD-H柱(0.46cm x 25cm);正己烷/异丙醇=98/2;流速=0.8毫升/分钟;检测波长=254nm;tR=31.07(minor),33.48(major)min].[α]D 20=+44.0°(c0.5,CHCl3)1H NMR(300MHz,CDCl3)δ=7.96(br s,1H),7.41-7.31(m,3H),7.19-7.12(m,4H),7.03(t,J=7.2Hz,1H),6.89(d,J=2.4Hz,1H),6.28(ddd,J=6.6,9.9,17.1Hz,1H),5.48(d,J=6.0Hz,1H),5.23(d,J=9.9Hz,1H),5.05(d,J=16.8Hz,1H).13C NMR(75MHz,CDCl3)δ=140.3,138.7,136.5,133.9,129.9,129.5,127.6,126.7,126.8,122.7,122.1,119.6,119.4,117.4,116.2,111.0,42.7.质谱(EI,m/z,rel.intensity)263(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C17H14NCl(M+):267.0815,实际值(Found):267.0814.IR(KBr):3418,3059,3008,2980,2924,2854,1637,1619,1592,1571,1548,1471,1457,1442,1418,1352,1338,1245,1221,1125,1095,1046,1036,1011,995,921,801,743cm-1.
P5:3-(1-(2-溴苯基)烯丙基)-1-氢-吲哚
黄色油状液体,Rf=0.2(正己烷-乙醚,10:1).b/1>99/1;41%收率,85%ee[手性AD-H(0.46cm x 25cm);正己烷/异丙醇=90/10;流速=1.0毫升/分钟;检测波长=254nm;tR=8.15(minor),11.24(major)min].[α]D 20=+86.8°(c0.5,CHCl3).1HNMR(300MHz,CDCl3)δ=8.00(br s,1H),7.59(d,J=7.5Hz,1H),7.36(t,J=8.1Hz,2H),7.19-7.00(m,5H),6.91(d,J=2.1Hz,1H),6.27(ddd,J=6.3,9.9,16.8Hz,1H),5.46(dd,J=1.2,6.0Hz,1H),5.24(dt,J=1.5,9.9Hz,1H),5.00(dt,J=1.5,16.8Hz,1H).13C NMR(75MHz,CDCl3)δ=142.0,138.8,136.6,132.8,130.1,127.9,127.4,126.7,124.8,122.7,122.1,119.7,119.4,117.6,116.3,111.0,45.5.质谱(EI,m/z,rel.intensity)311(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C17H14NBr(M+):311.0310,实际值(Found):311.0311.IR(KBr):3418,3056,2959,2923,2853,1636,1459,1437,1417,1337,1221,1095,1022,921,743cm-1.
P6:3-(1-(1-萘基)烯丙基)-1-氢-吲哚
黄色油状液体,Rf=0.2(正己烷-乙醚,10:1).b/1>99/1;92%收率(56.9mg),82%ee.[手性AD-H(0.46cm x 25cm);正己烷/异丙醇=90/10;流速=1.0毫升/分钟;检测波长=254nm;tR=16.84(major),30.83(minor)min].[α]D 20=+59.2°(c1.0,CHCl3).1H NMR(300MHz,CDCl3)δ=8.08(d,J=7.5Hz,1H),7.85-7.70(m,3H),7.44-7.37(m,4H),7.17-7.12(m,1H),6.89(d,J=2.4Hz,1H),6.82(dd,J=2.7,8.7Hz,1H),6.57(d,J=2.1Hz,1H),6.40(ddd,J=6.0,9.9,16.8Hz,1H),5.66(d,J=6.3Hz,1H),5.24(d,J=10.2Hz,1H),5.00(d,J=16.8Hz,1H),3.71(s,3H).13C NMR(75MHz,CDCl3)δ=153.6,139.7,138.7,133.9,131.7,131.6,128.6,127.2,127.0,125.8,125.7,125.4,125.3,124.2,124.1,117.5,116.2,111.8,111.7,101.5,55.7,42.1.质谱(EI,m/z,rel.intensity)313(M+,100);HRMS-EI:m/z[M]+计算值(calcd for)C22H19NO(M+):313.1467,实际值(Found):313.1472.IR(KBr):3424,3051,3001,2934,2830,1718,1636,1625,1596,1583,1508,1484,1456,1438,1209,1172,1045,1027,921,800,781cm-1。
Claims (7)
2、一种合成光学纯的基于联萘二酚骨架的磷氮类化合物的方法,其特征是在有机溶剂中,-78℃~120℃下,以光学纯的联萘二酚类化合物、三氯化磷、光学纯的四氢喹啉和吲哚啉类化合物为原料,在碱的作用下反应8-24小时制得磷氮类化合物;
上述的光学纯的联萘二酚类化合物、三氯化磷、四氢喹啉和吲哚啉类化合物、碱的摩尔比为1:1-1.5:1-1.5:3-10;
所述的光学纯的联萘二酚类化合物结构式为具有如下所示结构式的Ra或者Sa构型的光学纯化合物:三氯化磷结构式为:PCl3;所述的手性四氢喹啉和吲哚啉类化合物是具有如下结构式的R或者S构型的光学纯的化合物:
所述的碱是三乙胺、1,8-二氮杂二环[5,4,0]十一碳-7-烯、1,5-二氮杂二环[4,3,0]壬-5-烯、三乙烯二胺、N,O-双(三甲基硅基)乙酰胺、碳酸铯、碳酸钾,磷酸钾、醋酸钾、磷酸钾、氢化钠、正丁基锂、二(三甲基硅基)氨基钠、二(三甲基硅基)氨基锂、二(三甲基硅基)氨基钾、甲醇钠、质子海绵、叔丁醇钾、叔丁醇钠或者二异丙基乙基胺;或者上述的碱和三氟磺酸银、氯化锂或分子筛添加剂的组合;其中碱和添加物的重量比为1:0.1-5。
其中R1、R2和n如权利要求1所述。
3、如权利要求2所述的合成基于联萘二酚骨架的磷氮类化合物的方法,其特征是所述的上述的光学纯的联萘二酚类化合物、三氯化磷、四氢喹啉和吲哚啉类化合物、碱的摩尔比为1:1-1.5:1-1.5:3-10。
4、如权利要求2所述的合成基于联萘二酚骨架的磷氮类化合物的方法,其特征是所述有机溶剂是苯、四氯化碳、石油醚、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二氧六环或乙腈。
5、如权利要求2所述的合成基于联萘二酚骨架的磷氮类化合物的方法,其特征是所得产物经过重结晶、薄层层析、柱层析或减压蒸馏的分离。
6、一种如权利要求1所述的基于联萘二酚骨架的磷氮类化合物用于制备不对称催化反应中的催化剂。
7、如权利要求6所述的基于联萘二酚骨架的磷氮类化合物用途,其特征是作为手性配体,和金属铱生成配合物,在金属铱催化的吲哚不对称傅克烯丙基烷基化反应中作为有效的催化剂。
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CN110003105A (zh) * | 2019-04-29 | 2019-07-12 | 中国科学院上海有机化学研究所 | 轴手性吡啶化合物、其制备方法及应用 |
CN111454136A (zh) * | 2019-01-22 | 2020-07-28 | 中国科学院上海高等研究院 | 用于催化偕二取代芳香烯烃的氢甲酰化反应的催化剂及其制备方法和用途 |
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CN111454136A (zh) * | 2019-01-22 | 2020-07-28 | 中国科学院上海高等研究院 | 用于催化偕二取代芳香烯烃的氢甲酰化反应的催化剂及其制备方法和用途 |
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CN110003105B (zh) * | 2019-04-29 | 2022-08-09 | 中国科学院上海有机化学研究所 | 轴手性吡啶化合物、其制备方法及应用 |
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