CN118108666A - Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof - Google Patents
Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN118108666A CN118108666A CN202410230056.XA CN202410230056A CN118108666A CN 118108666 A CN118108666 A CN 118108666A CN 202410230056 A CN202410230056 A CN 202410230056A CN 118108666 A CN118108666 A CN 118108666A
- Authority
- CN
- China
- Prior art keywords
- ion
- chiral
- pye
- reaction
- ligand
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 74
- 150000001875 compounds Chemical class 0.000 title claims abstract description 68
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 19
- 238000006467 substitution reaction Methods 0.000 claims abstract description 16
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 14
- 230000003197 catalytic effect Effects 0.000 claims abstract description 12
- -1 3, 5-bis (trifluoromethyl) phenyl Chemical group 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 20
- 239000000758 substrate Substances 0.000 claims description 14
- 229910052723 transition metal Inorganic materials 0.000 claims description 14
- 150000003624 transition metals Chemical class 0.000 claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 239000002994 raw material Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical group [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical group [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical group [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 229940085991 phosphate ion Drugs 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000012018 catalyst precursor Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 239000012300 argon atmosphere Substances 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 77
- 238000003786 synthesis reaction Methods 0.000 abstract description 22
- 230000015572 biosynthetic process Effects 0.000 abstract description 20
- 238000000034 method Methods 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 4
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 21
- 229910052786 argon Inorganic materials 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 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 7
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000002274 desiccant Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical group [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000000746 allylic group Chemical group 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [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 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 2
- ZAPYLSLVQJQGEY-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalen-2-amine Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3N)=CC=CC2=C1 ZAPYLSLVQJQGEY-UHFFFAOYSA-N 0.000 description 2
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 2
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 description 2
- 235000000621 Bidens tripartita Nutrition 0.000 description 2
- 240000004082 Bidens tripartita Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 208000006637 fused teeth Diseases 0.000 description 2
- 238000007172 homogeneous catalysis Methods 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical group N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- SUXIPCHEUMEUSV-UHFFFAOYSA-N 4-bromoquinoline Chemical compound C1=CC=C2C(Br)=CC=NC2=C1 SUXIPCHEUMEUSV-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000006579 Tsuji-Trost allylation reaction Methods 0.000 description 1
- QWJYDTCSUDMGSU-UHFFFAOYSA-N [Sn].[C] Chemical class [Sn].[C] QWJYDTCSUDMGSU-UHFFFAOYSA-N 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000000080 chela (arthropods) Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011984 grubbs catalyst Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 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
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis and chiral catalysis, and discloses an axillary nitrogen ligand (PYEs type ligand) with flexible electron supply characteristics. The chiral ligand provided by the invention is mainly structurally characterized by comprising binaphthyl, H8 binaphthyl shaft chiral frameworks, shaft chiral frameworks and a nitrogen ligand with flexible electron supply characteristics. The chiral binaphthyl PYEs ligand provided by the invention can be directly used for catalyzing simple asymmetric allyl substitution reaction, has excellent enantioselectivity and higher catalytic activity, and shows excellent activity in the asymmetric allyl substitution catalytic reaction, the yield can reach 95%, and the enantioselectivity can reach 95%. The method has mild reaction conditions, high efficiency and certain practical value, and is suitable for large-scale production. Meanwhile, the structure enriches PYEs ligand families and provides a certain thought for chiral catalysis and synthesis of chiral compounds.
Description
Technical Field
The invention belongs to the technical field of organic synthesis and chiral catalysis, and relates to a preparation method of an axial chiral ligand nitrogen-nitrogen double-tooth, single-tooth or heterozygous nitrogen ligand (PYE) and application of the ligand in simple asymmetric allyl substitution reaction.
Background
Ligands have played a vital role in transition metal catalysis. The ligand and the metal coordinate to change the electronic property of the metal center, the steric hindrance of the ligand can influence the space environment of the metal to participate in the reaction, the structure and the reactivity of the metal coordination center are strongly controlled, meanwhile, the most challenging in organic chemistry is to synthesize chiral compounds, which are generally intermediates for preparing various medicines, fine chemical products and natural products, and today, asymmetric catalysis of transition metal becomes one of the most effective and direct chiral generation processes, which is not separated from efficient metal catalysts. Therefore, the design and development of novel ligands has important scientific significance for advancing research in the fields of homogeneous catalysis, coordination chemistry and organometallic chemistry.
Pi-acid ligands predominate in transition metal homogeneous catalysis studies. Pi-acid ligand not only can provide lone pair electrons for central atoms to form sigma-coordination bonds, but also can receive feedback electrons of the central atoms by self-empty pi-orbitals. Such as phosphines, amines (pyridine, oxazolines), and the recently rapidly evolving N-heterocyclic carbene ligands (N-Heterocyclic Carbene abbreviated NHC. Such ligands have achieved significant achievements in transition metals DiPAMP-chiral bisphosphine ligands developed as taught by William S. Knowles [ knowles. W.S. Acc. Chem. Res.1983,16,106.]; ryoji Noyori teaches the developed chiral spiro-nitrogen-phosphine ligand family-SIPHOS and SIPHOS-PE [ Xie, J. ], Z.Q. -L.acta Chim. Sinica 2014,72,778.], and Robert Howard Grubbs teaches the developed carbenb ligand-containing Grubbs catalyst [ Grubbs, R.H.; wenzel, A.G.eds.Handbook of Metathesis nd Ed.; wiley-VCH: weinheim, germany,2015 et al, which can demonstrate the important value of pi-acid ligands for transition metal catalysis.
It has been demonstrated in known relevant reports that the electron donating ability of PYEs system ligands can be compared to pyridine, azacyclic carbenes, and even some electron rich phosphine ligands. Johnson group studies reported that the [ Ni (0) p-PYE ] complex can efficiently and selectively activate the C-F bond to undergo oxidative addition; meanwhile, the TEP (Tolman Electronic Parameter Torrman electronic parameter) parameter of cis- [ (CO) 2 RhCl (PYE) ] complex is utilized to verify that the PYE ligand has the electron-donating ability comparable to NHC. The electron donating ability between the rhodium complex and the rhodium complex is compared by infrared comparison of the wave numbers of CO, the average value of NHC given in the literature in the lower graph is 2039cm -1, and the average value of PYEs ligand is 2038cm -1. It can be seen that PYEs ligand electron donating ability is similar to NHC [ Doster, m.e.; johnson, s.a. angelw.chem.int.ed.2009, 48,2185 ]. In recent years, development of ligands based on PYEs systems and research on their transition metal coordination have been advanced. For example, the Johnson group reports Ni-PYEs catalyzed C-H bond activated carbon tin coupling reaction studies [ Doster, M.E.; hatnean, j.a.; jeftic, t.; modi, S.; johnson, s.a.j.am.chem.soc.2010,132,11923 ]. The reported ligand design and development directions have focused on: firstly, from the coordination angle, the synthesis and coordination research of PYEs from single tooth to chelate double tooth, pincer type, multi-tooth and Hybrid with NHC (Hybrid); and secondly, on the electronic effect of the structure, synthesizing and coordination research of a mesoionic or mesoionic ligand based on the ortho, meta and para substituted pyridine aromatic ring. However, the related ligand PYEs with chiral structure as main skeleton has less research, and only one example of synthesis and coordination research based on carbon center chiral (R, R) -1, 2-cyclohexanediamine skeleton o-PYEs ligand is available, but no attempt is made to catalyze the reaction.
The Asymmetric Allyl Substitution (AAS) is a catalytic reaction method that can directly and effectively construct various chiral molecules, and is one of the powerful methods for forming carbon-carbon bonds and carbon heterobonds. While palladium-catalyzed AAS reactions have mild conditions and high functional group tolerance, palladium-catalyzed asymmetric allylic alkylation reactions have been reported for the first time from Trost, and have been of interest to researchers.
Disclosure of Invention
The invention provides a method for developing and synthesizing PYEs compounds with corresponding axial chirality by taking racemic, optical pure binaphthyl amine or hydrogenated binaphthyl amine which are cheap and easy to obtain as raw materials, wherein the method comprises enantiomer, diastereoisomer, racemate or catalytic acceptable salt thereof.
The primary object of the present invention is to provide a class of axial chiral ligand nitrogen-nitrogen bidentate or monodentate nitrogen ligands (PYEs).
It is another object of the present invention to provide a process for the preparation of the above PYE compounds.
The invention also provides application of the ligand in simple asymmetric allyl substitution reaction.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides an axial chiral PYE nitrogen ligand compound, which has a structural formula as shown in the following formula I or formula II:
wherein R 1 is selected from alkyl of C 1~C22, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;
r 2 is selected from the group consisting of hydrogen, C 1~C22 alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C 5~C6 aromatic heterocyclic substituents;
R 4 is selected from the group consisting of hydrogen, C 1~C22 alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C 5~C6 aromatic heterocyclic substituents;
R 3,R5,R6 is selected from hydrogen, hydrocarbon group of C 1~C22, phenyl;
X is selected from halogen ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethane sulfonate ion, sulfate ion, phosphate ion, acetate ion, hydroxide ion, tartrate ion.
Ring a is selected from the group consisting of an aliphatic ring of C 5~7, an aliphatic heterocyclic ring of C 5~7, a substituted aromatic ring of C 5~6, and an aromatic heterocyclic ring of C 5~6.
Preferably, the aromatic heterocycle of C 5~C6 is pyridine, pyrrole or thiophene.
Preferably, the heterocycle is an oxygen-, nitrogen-or sulfur-containing heterocycle.
More preferably, the structural formula is any one of the following:
Wherein R1 is selected from C 1~C22 alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl, R is selected from C 1~C5 alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;
X is selected from halogen ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethane sulfonate ion, sulfate ion, phosphate ion, acetate ion, hydroxide ion, tartrate ion.
Further, halogen is chlorine, bromine or iodine.
In addition, the compounds include enantiomers, diastereomers, racemates or catalytically acceptable salts of the structural formulae.
The invention also protects the application of the axial chiral PYE nitrogen ligand compound in asymmetric catalytic reaction. Further, it is an asymmetric catalytic substitution reaction for catalyzing simple allyl substitution.
More specifically, the asymmetric catalytic reaction is to take the axial chiral PYE nitrogen ligand compound as a raw material in an organic solvent, add a palladium catalyst precursor with catalytic equivalent, then add a common allyl substituted substrate, dicarbonyl compound and alkali, and stir and react for 24-48 hours in an argon atmosphere to obtain a chiral substituted product. Further, the molar ratio of the allyl substituted substrate to the axichiral PYE-like nitrogen ligand compound is 100: 10-100: 1, a step of; the concentration of the allyl substituted substrate is 0.01M-0.1M; the alkali is potassium carbonate, cesium carbonate, BSA+potassium acetate, potassium tert-butoxide and sodium tert-butoxide; the concentration of alkali is 0.01M-0.2M, and the reaction temperature is 0-40 ℃; the selected organic solvent is one or more of toluene, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, 1, 4-dioxane and xylene; the catalyst precursor is allylpalladium (II) chloride dimer, tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium or palladium acetate.
The ligand compound provided by the invention can be used for preparing chiral compounds of various transition metals besides the catalytic reaction, for example, the axial chiral PYE nitrogen ligand compound is coordinated with the transition metal to obtain the corresponding metal catalyst. The transition metal may be iron, nickel, palladium, copper, rhodium, silver, platinum, etc.
The invention also provides a method for preparing the catalyst (axial chiral PYE nitrogen ligand compound) as follows:
Wherein R 1~R6 in formulas 1,2,3, 4,5, 6, 7 are as defined in claim 1, and G is selected from the group consisting of nitrogen, phosphorus, oxygen, sulfur, and other heteroatom groups.
The preparation steps are briefly described as follows: in the presence of an organic solvent, alkali and a palladium catalyst, a compound shown in a formula 1 reacts with a compound shown in a formula 2 in a reactor for 4-24 hours to prepare a compound shown in a formula 3; in the presence of an organic solvent, carrying out substitution reaction on a compound shown in a formula 3 and an electrophile to obtain a compound shown in a formula 4; in the presence of a small amount of organic solvent, partially alkalizing the compound shown in the formula 4 to obtain a compound shown in the formula 5; wherein the above method is referred to in such a manner that the substrate represented by formula 6 synthesizes the corresponding nitrogen ligand compound.
In the above synthetic method, the organic solvent is one or more of methanol, ethanol, acetonitrile, tetrahydrofuran, toluene, xylene, diethyl ether, dioxane, dichloromethane and chloroform; the alkali is sodium tert-butoxide, potassium tert-butoxide and sodium hydroxide; the electrophile is iodo alkane, benzyl bromide, chloro alkane and methyl triflate; the palladium catalyst is tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium and palladium acetate.
Compared with the prior art, the invention has the beneficial effects that:
The chiral binaphthyl PYEs ligand provided by the invention can be directly used for catalyzing simple asymmetric allyl substitution reaction, has excellent enantioselectivity and higher catalytic activity, and shows excellent activity in the asymmetric allyl substitution catalytic reaction, the yield can reach 95%, and the enantioselectivity can reach 95%. The method has mild reaction conditions, high efficiency and certain practical value, and is suitable for large-scale production. Meanwhile, the structure enriches PYEs ligand families and provides a certain thought for chiral catalysis and synthesis of chiral compounds.
Drawings
FIG. 1 is a schematic structural diagram of a chiral compound obtained by coordination of an L1 ligand and a transition metal.
FIG. 2 is a schematic structural diagram of a chiral compound obtained by coordination of an L2 ligand and a transition metal.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The test methods used in the embodiment of the invention are all conventional methods unless specified otherwise; the materials, reagents and the like used, unless otherwise specified, are those commercially available.
EXAMPLE 1 Synthesis of Compound [ R-1]
In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after air was replaced three times with argon, toluene (10 mL) was added, stirred for 10min, 4-bromopyridine hydrochloride (583.5 mg,4 mmol) was added, and the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the consumption of the starting material. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) gave the title compound as a yellow solid in yield 90%.1HNMR(400MHz,Acetonitrile-d3)δ8.06(d,J=8.9Hz,2H),7.98(d,J=8.2Hz,2H),7.88(d,J=6.0Hz,4H),7.68(d,J=8.9Hz,2H),7.44(ddd,J=8.2,6.8,1.2Hz,2H),7.25(ddd,J=8.3,6.8,1.3Hz,2H),7.06(dd,J=8.4,1.1Hz,2H),6.63(d,J=6.6Hz,4H).13C NMR(101MHz,DMSO-d6)δ152.80,147.61,136.94,134.18,131.57,129.74,128.72,127.06,126.11,125.85,125.49,123.62,109.80.
EXAMPLE 2 Synthesis of Compound [ R-2]
Substrate [ R-1] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target product as a yellow solid in the yield 89%.1H NMR(400MHz,Acetonitrile-d3)δ9.28(s,2H),8.13(d,J=8.8Hz,2H),7.99(dd,J=7.9,3.3Hz,6H),7.53(d,J=8.8Hz,2H),7.48(ddd,J=8.2,6.7,1.2Hz,2H),7.29(ddd,J=8.3,6.8,1.3Hz,2H),7.13(d,J=8.5Hz,2H),7.06–6.95(m,4H),3.86(s,6H).13C NMR(101MHz,Acetonitrile-d3)δ156.17,144.13,133.64,133.59,132.99,131.01,130.04,128.65,127.68,127.06,126.15,124.38,109.57,45.42.
EXAMPLE 3 Synthesis of Compound L1
20ML of a 5M NaOH aqueous solution prepared in advance is added into a reaction flask filled with a magneton, 2mL of methanol is used for dissolving a compound [ R-2], the mixture is dropwise added into the reaction flask which is vigorously stirred, after all the mixture is added, an oil bath of the system is heated to 50 ℃, after the mixture is heated for 30-60min, the system is cooled to room temperature, and the solid is filtered to obtain a target compound as a yellow solid. Yield is good 70%.1H NMR(400MHz,Methylene Chloride-d2)δ7.70(dd,J=8.4,4.6Hz,4H),7.15(ddd,J=8.1,6.5,1.4Hz,2H),7.07(d,J=8.7Hz,2H),7.00(ddd,J=8.1,6.6,1.3Hz,2H),6.95(d,J=8.3Hz,2H),6.55(d,J=37.4Hz,4H),5.87(d,J=40.9Hz,4H),3.22(s,6H).13C NMR(101MHz,Methylene Chloride-d2)δ156.01,149.20,137.40,136.46,134.65,130.07,127.74,127.60,126.46,125.64,125.25,122.97,122.93,115.79,108.51,42.18.
EXAMPLE 4 Synthesis of Compound [ R-3]
In a reaction schlenk tube filled with magnetons, a substrate [ R-1] (438 mg,1 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, phCH2Br (1.7 g,10 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on a silica gel column (CH 2Cl2: meoh=20:1) to give the target product as a yellow solid in the yield of 86%.1HNMR(500MHz,Methanol-d4)δ8.17(d,J=7.4Hz,4H),8.14(d,J=8.8Hz,2H),8.00(d,J=8.2Hz,2H),7.62(d,J=8.8Hz,2H),7.49(ddd,J=8.2,6.9,1.2Hz,2H),7.43–7.34(m,10H),7.28(ddd,J=8.3,6.8,1.3Hz,2H),7.12(dd,J=8.4,1.0Hz,2H),6.87(d,J=7.6Hz,4H),5.35(s,4H).13C NMR(126MHz,Methanol-d4)δ156.37,143.02,134.69,133.49,133.47,132.95,130.71,129.16,129.07,128.62,128.43,128.15,127.31,126.62,125.94,123.36,60.75.
EXAMPLE 5 Synthesis of Compound L2
Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-3] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound, yellow solid and obtaining the yield 81%.1H NMR(500MHz,Methanol-d4)δ7.80(d,J=8.8Hz,2H),7.77(d,J=8.1Hz,2H),7.37(ddt,J=8.1,6.5,1.2Hz,4H),7.35–7.30(m,2H),7.25(ddd,J=8.0,6.6,1.3Hz,2H),7.21–7.10(m,8H),7.07(ddd,J=8.0,6.6,1.3Hz,2H),7.02(ddt,J=8.5,1.4,0.7Hz,2H),6.12(s,4H),4.85–4.75(m,4H).13C NMR(126MHz,Chloroform-d)δ155.71,147.98,137.26,136.22,136.10,134.67,130.33,129.14,128.48,127.99,127.61,127.39,126.47,126.39,125.40,123.39,123.20,115.68,108.80,58.80.
EXAMPLE 6 Synthesis of Compound R-4
In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and air were added three times after replacing air with argon, toluene (10 mL) was added, and after stirring for 10min, 3-bromopyridine (583.5 mg,3 mmol) was added, the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the consumption of the starting materials. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=50:1) afforded the title compound [ R-4] as a yellow solid in yield 87%.1H NMR(400MHz,Chloroform-d)δ8.19(d,J=2.7Hz,2H),8.12(dd,J=4.7,1.4Hz,2H),7.93(d,J=8.9Hz,2H),7.90–7.85(m,2H),7.60(d,J=8.9Hz,2H),7.37(ddd,J=8.0,6.7,1.2Hz,2H),7.30–7.26(m,5H),7.23(ddd,J=8.3,2.8,1.5Hz,3H),7.18–7.12(m,2H),7.05(dd,J=8.2,4.7Hz,2H),5.49(s,2H).13C NMR(101MHz,Chloroform-d)δ142.83,141.35,139.38,139.11,133.90,130.09,130.01,128.51,127.54,125.41,124.57,124.36,123.80,118.16,118.12.
EXAMPLE 7 Synthesis of Compound L3
In a schlenk tube containing magnetons, a substrate [ R-4] (100 mg,0.23 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target L3 as a yellow solid in the yield of 90%.1H NMR(400MHz,Acetonitrile-d3)δ8.27(t,J=1.9Hz,2H),8.08(d,J=8.8Hz,2H),7.99(d,J=8.2Hz,2H),7.90–7.79(m,6H),7.65(d,J=8.8Hz,2H),7.51–7.39(m,4H),7.31(ddd,J=8.3,6.8,1.3Hz,2H),7.15(d,J=8.5Hz,2H),4.00(s,6H).13C NMR(101MHz,Acetonitrile-d3)δ146.35,136.45,135.13,134.66,132.99,131.75,131.49,129.47,129.38,128.22,128.06,127.41,126.68,126.40,123.66,118.21,49.10.
EXAMPLE 8 Synthesis of Compound R-5
In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after replacing air with argon three times, toluene (10 mL) was added, and after stirring for 10min, 2-bromopyridine (583.5 mg,2 mmol) was added, and the mixture was heated to 100℃in an oil bath, and the progress of the reaction was monitored by TLC and the reaction was stopped after the consumption of the starting material. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=100:1) afforded the title compound [ R-5] as a yellow solid in yield 80%.1H NMR(400MHz,Chloroform-d)δ8.12(d,J=8.9Hz,2H),8.03(dd,J=5.2,1.9Hz,2H),7.98(d,J=9.0Hz,2H),7.90(d,J=8.1Hz,2H),7.37(ddd,J=8.1,6.7,1.2Hz,2H),7.28-7.19(m,4H),7.12(d,J=8.4Hz,2H),6.62-6.57(m,2H),6.54(d,J=8.4Hz,2H),6.26(s,2H).13C NMR(101MHz,Chloroform-d)δ155.59,148.05,137.58,137.54,133.71,130.59,129.53,128.34,127.13,125.12,124.61,121.13,120.34,115.50,109.49.
EXAMPLE 9 Synthesis of Compound R-6
Substrate [ R-5] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target compound [ R-6] as a yellow solid in the yield 94%.1HNMR(400MHz,Acetonitrile-d3)δ9.26(s,2H),8.11(d,J=8.8Hz,2H),7.98(dd,J=7.9,3.3Hz,6H),7.52(d,J=8.8Hz,2H),7.46(ddd,J=8.2,6.7,1.2Hz,2H),7.28(ddd,J=8.3,6.8,1.3Hz,2H),7.12(d,J=8.5Hz,2H),6.98(d,J=6.3Hz,4H),3.85(s,6H).13C NMR(101MHz,Acetonitrile-d3)δ156.59,144.56,134.07,134.01,133.41,131.43,130.46,129.07,128.10,127.49,126.58,124.81,109.99,45.84.
EXAMPLE 10 Synthesis of Compound L4
Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-6] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound, yellow solid L4, and obtaining the yield 81%.1H NMR(400MHz,Chloroform-d)δ7.77–7.71(m,4H),7.33(dd,J=8.5,1.2Hz,2H),7.23–7.06(m,6H),6.67(dd,J=6.9,1.8Hz,2H),6.52(ddd,J=9.4,6.3,1.8Hz,2H),6.34(dd,J=9.5,1.3Hz,2H),5.46(td,J=6.6,1.4Hz,2H),2.79(s,6H).13C NMR(101MHz,Chloroform-d)δ151.56,147.06,138.42,134.61,134.23,129.87,127.74,127.43,126.85,126.60,125.13,123.39,122.82,114.68,102.07,39.22.
EXAMPLE 11 Synthesis of Compound R-7
In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), (R) -5,5', 6', 7', 8' -octahydro- [1,1 '-binaphthyl ] -2,2' -diamine (293 mg,1 mmol), sodium t-butoxide (768.8 mg,8 mmol) was added, after replacing air three times with argon, toluene (10 mL) was added, stirring was performed for 10min, 4-bromopyridine hydrochloride (583.5 mg,4 mmol) was added, the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) afforded the title compound [ R-7] as a yellow solid in yield 85%.1H NMR(400MHz,Chloroform-d)δ8.08(d,J=5.7Hz,4H),7.23(d,J=8.2Hz,2H),7.12(d,J=8.3Hz,2H),6.60(d,J=6.3Hz,5H),5.75(s,2H),2.79(t,J=6.2Hz,4H),2.15(t,J=6.3Hz,4H),1.79-1.51(m,5H).13C NMR(101MHz,DMSO-d6)δ153.72,145.88,136.81,134.79,134.12,132.75,129.15,122.24,108.47,29.10,27.09,22.47,22.19.
EXAMPLE 12 Synthesis of Compound R-8
Substrate [ R-7] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target compound [ R-8] as a yellow solid in the yield 92%.1H NMR(400MHz,Methanol-d4)δ8.02(d,J=7.2Hz,4H),7.27(d,J=8.2Hz,2H),7.20(d,J=8.2Hz,2H),6.77(s,4H),3.96(s,6H),2.90(t,J=6.1Hz,4H),2.34–2.15(m,4H),1.88–1.73(m,8H).13C NMR(101MHz,Methanol-d4)δ157.60,144.97,139.41,139.34,133.89,133.17,131.34,123.75,45.58,30.78,28.64,23.91,23.56.
EXAMPLE 13 Synthesis of Compound L5
20ML of a 5M NaOH aqueous solution prepared in advance is added into a reaction flask filled with a magneton, 2mL of methanol is used for dissolving a compound [ R-8], the mixture is dropwise added into the reaction flask which is vigorously stirred, after all the mixture is added, an oil bath of the system is heated to 50 ℃, after the mixture is heated for 30-60min, the system is cooled to room temperature, and the solid is filtered to obtain a target compound L5 as a yellow solid. Yield is good 67%.1HNMR(400MHz,Methylene Chloride-d2)δ6.76(d,J=8.0Hz,2H),6.55(dd,J=7.8,2.3Hz,2H),6.45(d,J=8.0Hz,2H),6.38(dd,J=7.8,2.2Hz,2H),5.88(dd,J=7.9,2.8Hz,2H),5.78(dd,J=7.8,2.8Hz,2H),3.18(s,6H),2.63(t,J=6.2Hz,4H),2.23–2.12(m,2H),1.96(dt,J=17.0,6.4Hz,2H),1.66–1.46(m,8H).13C NMR(101MHz,Methylene Chloride-d2)δ155.96,148.67,137.45,136.72,136.47,133.67,130.52,127.95,118.48,115.91,108.80,42.39,30.03,27.67,23.91,23.59.
EXAMPLE 14 Synthesis of Compound R-9
In a flask equipped with a magneton reaction vessel, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after air was replaced three times with argon, toluene (10 mL) was added and stirred for 10min, 4-bromoquinoline (832 mg,4 mmol) was added, and the mixture was heated to 100℃in an oil bath, and the reaction was stopped after the completion of the consumption of the raw materials by TLC. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) afforded the title compound [ R-9] as a yellow solid in yield 90%.1H NMR(500MHz,Chloroform-d)δ8.36(d,J=5.2Hz,2H),8.03(d,J=8.9Hz,2H),7.96(t,J=8.9Hz,4H),7.80(d,J=8.9Hz,2H),7.58(ddd,J=8.3,6.8,1.3Hz,2H),7.50(td,J=7.2,6.7,1.1Hz,2H),7.39(td,J=7.5,6.8,1.2Hz,2H),7.30(d,J=8.4Hz,2H),7.27–7.22(m,2H),7.16(d,J=8.4Hz,2H),6.93(d,J=5.2Hz,2H),6.34(s,2H).13C NMR(126MHz,Chloroform-d)δ150.60,149.00,146.32,137.12,133.60,131.01,130.24,130.17,129.57,128.83,127.93,125.70,125.55,124.90,121.69,121.10,120.33,119.54,103.45.
EXAMPLE 15 Synthesis of Compound R-10
In a reaction schlenk tube filled with magnetons, a substrate [ R-9] (100 mg,0.19 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, phCH 2 Br (178 mg,10 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on a silica gel column (CH 2Cl2: meoh=20:1) to give the target compound [ R-10] as a yellow solid in the yield 81%.1H NMR(400MHz,Methanol-d4)δ8.32(d,J=8.4Hz,2H),7.97(d,J=8.6Hz,2H),7.91–7.79(m,4H),7.56(dd,J=11.3,6.4Hz,6H),7.41–7.29(m,4H),7.26–7.13(m,12H),6.98–6.90(m,4H),6.51(d,J=7.5Hz,2H),5.51–5.31(m,4H).
EXAMPLE 16 Synthesis of Compound L6
Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-10] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound L2 and a yellow solid [ L6], and obtaining the yield 68%.1H NMR(400MHz,Methylene Chloride-d2)δ7.94(d,J=8.0Hz,2H),7.68(t,J=9.1Hz,4H),7.26–7.03(m,16H),6.96(d,J=7.3Hz,4H),6.87–6.77(m,4H),6.54(d,J=8.0Hz,2H),5.86(d,J=7.9Hz,2H),4.80(d,J=16.9Hz,2H),4.68(d,J=16.8Hz,2H).13C NMR(101MHz,Methylene Chloride-d2)δ153.73,139.29,138.98,136.29,134.49,130.32,128.92,127.89,127.83,127.68,126.22,126.14,126.08,125.88,125.58,125.30,123.18,122.94,122.54,114.93,102.40,55.36.
Application example 1
The ligands prepared in example 3 and example 5 were used in asymmetric allylic substitution reactions of the following formulas. The following is the product P1 produced by catalysis: allyl palladium (II) chloride dimer (2 mol%) chiral nitrogen ligand (4.4 mol%), potassium carbonate (3 eq.) were added sequentially to a10 mL schlenk tube, after 3 argon changes, 3mL toluene was added, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, dimethyl malonate (3 eq.) was added, reaction was performed at room temperature for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate the target product P1. The catalytic results are shown in Table 1 below.
/>
TABLE 1 catalytic results
Sequence number | Ligand | Yield (%) | ee(%) |
1 | L1 | 93 | 91 |
2 | L2 | 99 | 95 |
Application example 2
The ligand prepared in example 5 was used in an asymmetric allylic substitution reaction, and the reaction formula is as follows. The following is the product P2 produced by catalysis: allyl palladium (II) chloride dimer (2 mol%), chiral nitrogen ligand (4.4 mol%), potassium carbonate (3 eq.) were added sequentially to a 10mL schlenk tube, 3mL toluene was added after 3 argon changes, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, tetrahydropyrrole (3 eq.) was added, reaction was performed at room temperature for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate to obtain a target product P2. The catalytic results are shown in Table 2 below.
TABLE 2 catalytic results graphs
Sequence number | Ligand | Yield (%) | ee(%) |
1 | L2 | 99 | 92 |
Application example 3
The ligand prepared in example 5 was used in an asymmetric allylic substitution reaction and the reaction formula was as follows. The following is the product P3 produced by catalysis: allyl palladium (II) chloride dimer (5 mol%), chiral nitrogen ligand (10 mol%), cesium carbonate (3 eq.) were added sequentially to a 10mL schlenk tube, after 3 argon changes, 3mL of 1, 4-dioxane was added, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, benzyl alcohol (3 eq.) was added, oil bath at 50 ℃ was performed for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate to obtain a target product P3.
The catalytic results are shown in Table 3 below:
Sequence number | Ligand | Yield (%) | ee(%) |
1 | L2 | 87 | 85 |
The ligand prepared in the example 3 is applied to a transition metal coordination reaction to obtain the target transition metal catalyst.
In addition, the L3 to L6 ligands have better effects with reference to the catalytic reaction, and show good prospects in asymmetric allyl substitution reaction.
Application example 4
The ligand prepared in example 3 was coordinated to copper and a single crystal structure was successfully obtained.
An amount of L1 ligand (30 mg,1 eq.) and Cu (ii) catalyst (1 eq.) were weighed into a reaction flask, 2mL DCM was added, stirred at room temperature for 2-6h, and tlc monitored the progress of the reaction. After the reaction, the reaction system was concentrated, and then the DCM diethyl ether was recrystallized to obtain the target product. The single crystal results verify that the absolute configuration of the ligand is the R configuration. The following data are single crystal characterization data:
/>
Application example 5
The ligand prepared in example 3 was coordinated with Pd and successfully obtained as a single crystal structure.
An amount of L1 ligand (30 mg,1 eq.) and Pd (ii) catalyst (1 eq.) were weighed into a reaction flask, 2mL DCM was added, stirred at room temperature for 2-6h, and tlc monitored the progress of the reaction. After the reaction, the reaction system was concentrated, and then the DCM diethyl ether was recrystallized to obtain the target product. The single crystal results verify that the absolute configuration of the ligand is the R configuration. The following data are single crystal characterization data:
/>
it should be understood that the foregoing description of the specific embodiments is merely illustrative of the invention, and is not intended to limit the invention, and that any modifications, equivalents, improvements, etc. that fall within the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (10)
1. An axial chiral PYE nitrogen ligand compound is characterized by being shown in the following formula I or formula II:
wherein R 1 is selected from alkyl of C 1~C22, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;
r 2 is selected from the group consisting of hydrogen, C 1~C22 alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C 5~C6 aromatic heterocyclic substituents;
R 4 is selected from the group consisting of hydrogen, C 1~C22 alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C 5~C6 aromatic heterocyclic substituents;
R 3,R5,R6 is selected from hydrogen, hydrocarbon group of C 1~C22, phenyl;
X is selected from halogen ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethane sulfonate ion, sulfate ion, phosphate ion, acetate ion, hydroxide ion, tartrate ion.
Ring a is selected from the group consisting of an aliphatic ring of C 5~7, an aliphatic heterocyclic ring of C 5~7, a substituted aromatic ring of C 5~6, and an aromatic heterocyclic ring of C 5~6.
2. The axichiral PYE nitrogen ligand compound of claim 1, wherein the aromatic heterocycle of C 5~C6 is pyridine, pyrrole or thiophene.
3. The axichiral PYE nitrogen ligand compound according to claim 1, wherein the heterocycle is an oxygen-, nitrogen-or sulfur-containing heterocycle.
4. The axial chiral PYE nitrogen ligand compound according to claim 1, wherein the structural formula is any one of the following:
Wherein R1 is selected from C 1~C22 alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl, R is selected from C 1~C5 alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;
X is selected from halogen ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethane sulfonate ion, sulfate ion, phosphate ion, acetate ion, hydroxide ion, tartrate ion.
5. The axichiral PYE nitrogen ligand compound of claim 4, wherein halogen is chlorine, bromine or iodine.
6. The axichiral PYE nitrogen ligand compound of claim 1, further comprising an enantiomer, diastereomer, racemate or a catalytically acceptable salt of said structural formula.
7. Use of an axichiral PYE nitrogen ligand compound according to claim 1 in an asymmetric catalytic reaction.
8. The use according to claim 7, characterized in that it is for catalyzing asymmetric catalytic substitution reactions of simple allyl substitution.
9. The use according to claim 7, wherein the asymmetric catalytic reaction is carried out in an organic solvent using the axichiral PYE nitrogen ligand compound as a raw material, adding a catalytic equivalent of palladium catalyst precursor, adding a commonly used allyl substituted substrate, dicarbonyl compound and alkali, and stirring under argon atmosphere for reacting for 24-48 hours to obtain chiral substituted product.
10. The use according to claim 7, wherein the axial chiral PYE nitrogen ligand compound is coordinated to a transition metal to give the corresponding metal catalyst.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410230056.XA CN118108666A (en) | 2024-02-29 | 2024-02-29 | Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410230056.XA CN118108666A (en) | 2024-02-29 | 2024-02-29 | Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN118108666A true CN118108666A (en) | 2024-05-31 |
Family
ID=91218540
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202410230056.XA Pending CN118108666A (en) | 2024-02-29 | 2024-02-29 | Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN118108666A (en) |
-
2024
- 2024-02-29 CN CN202410230056.XA patent/CN118108666A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2563799B1 (en) | Ruthenium complex and method for preparing optically active alcohol compound | |
CA2382779C (en) | Chiral ligands, transition-metal complexes thereof and uses thereof in asymmetric reactions | |
CN108659046A (en) | Monophosphorus ligand and its intermediate and preparation method based on tetramethyl spiro indan skeleton and purposes | |
EP4089097A1 (en) | Preparation method for and application of chiral spirocyclic phosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof | |
CN112961194B (en) | PNO ligand containing chiral ferrocene and application thereof | |
Jayaraj et al. | Coordination versatility of NHC-metal topologies in asymmetric catalysis: Synthetic insights and recent trends | |
WO2015102020A1 (en) | Novel n-heterocyclic carbene compounds, their preparation and use | |
CN110494439B (en) | Chiral biphenyl diphosphine ligand and preparation method thereof | |
CN102391306B (en) | Spirobenzylamine-phosphine and preparation method and application thereof | |
AU2011301115B2 (en) | Biaryl diphosphine ligands, intermediates of the same and their use in asymmetric catalysis | |
CN105017150B (en) | A kind of method of the outer amine of the amine asymmetric hydrogenation synthesis of chiral ring of palladium chtalyst quinoline 3 | |
CN109593085B (en) | Pyridine-amide-oxazoline ligand, synthetic method thereof, metal complex thereof and application thereof | |
CN111320651B (en) | Chiral amino-pyridine-phosphine tridentate ligand, manganese complex, preparation method and application thereof | |
CN118108666A (en) | Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof | |
CN107286089B (en) | O-bicyclic amine compound, preparation method thereof and chiral product | |
CN109666044B (en) | Organophosphorus compound based on [2.2] p-cyclophane alkyl skeleton and intermediate, preparation method and application thereof | |
JP7464234B2 (en) | Method for producing highly optically active allene carboxylic acid compounds having axial asymmetry | |
CN112142790B (en) | Chiral pincer-like compound and palladium or nickel complex thereof and synthesis method | |
WO2013153408A1 (en) | Catalyst compounds | |
CN113527360B (en) | Phosphine-nitrogen ligand and application of complex thereof in catalyzing asymmetric reaction | |
CN114085251B (en) | Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof | |
ES2551894T3 (en) | Paracyclofan-based ligands, their preparation and use in catalysis | |
CN110938086B (en) | Half-sandwich ruthenium-thione complex and preparation method thereof, ammonia borane hydrolysis method and nitrobenzene compound reduction method | |
EP1747205A1 (en) | Pharmaceutical compositions | |
JP2008247881A (en) | Catalyst for coupling and ligand used for the same and method for producing compound having biaryl structure by cross coupling reaction |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |