WO2008148202A1 - Method for the preparation of aminophosphine ligands and their use in metal catalysts - Google Patents
Method for the preparation of aminophosphine ligands and their use in metal catalysts Download PDFInfo
- Publication number
- WO2008148202A1 WO2008148202A1 PCT/CA2008/001076 CA2008001076W WO2008148202A1 WO 2008148202 A1 WO2008148202 A1 WO 2008148202A1 CA 2008001076 W CA2008001076 W CA 2008001076W WO 2008148202 A1 WO2008148202 A1 WO 2008148202A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- groups
- optionally substituted
- alkyl
- ring system
- linked
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 99
- 239000003446 ligand Substances 0.000 title claims abstract description 70
- XQJHRCVXRAJIDY-UHFFFAOYSA-N aminophosphine Chemical compound PN XQJHRCVXRAJIDY-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 45
- 239000002184 metal Substances 0.000 title claims abstract description 45
- 239000003054 catalyst Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 73
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims description 153
- 125000002950 monocyclic group Chemical group 0.000 claims description 105
- 150000001875 compounds Chemical class 0.000 claims description 80
- 125000004429 atom Chemical group 0.000 claims description 78
- 229920006395 saturated elastomer Polymers 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 62
- 125000004432 carbon atom Chemical group C* 0.000 claims description 59
- 125000004437 phosphorous atom Chemical group 0.000 claims description 54
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 229910052760 oxygen Inorganic materials 0.000 claims description 43
- -1 9-fluorenylmethyloxycarbonyl Chemical group 0.000 claims description 40
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000004122 cyclic group Chemical group 0.000 claims description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000003367 polycyclic group Chemical group 0.000 claims description 22
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 21
- 125000003277 amino group Chemical group 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 16
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 13
- RYSREGABYNTRPR-UHFFFAOYSA-N 1h-phosphepin-2-amine Chemical compound NC1=CC=CC=CP1 RYSREGABYNTRPR-UHFFFAOYSA-N 0.000 claims description 12
- 125000005466 alkylenyl group Chemical group 0.000 claims description 12
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 150000002576 ketones Chemical class 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 150000002466 imines Chemical class 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 229910052723 transition metal Inorganic materials 0.000 claims description 5
- 150000003624 transition metals Chemical class 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 4
- 229910018965 MCl2 Inorganic materials 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 125000006242 amine protecting group Chemical group 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 3
- 125000005610 enamide group Chemical group 0.000 claims description 3
- 125000002346 iodo group Chemical group I* 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 150000004696 coordination complex Chemical class 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 8
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 4
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 3
- MNKCOIOOGRJIGH-UHFFFAOYSA-N P.NP Chemical compound P.NP MNKCOIOOGRJIGH-UHFFFAOYSA-N 0.000 abstract 3
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 150000003512 tertiary amines Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 98
- 239000000243 solution Substances 0.000 description 75
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 72
- 239000000203 mixture Substances 0.000 description 67
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
- 239000000047 product Substances 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- 238000004679 31P NMR spectroscopy Methods 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 229910000085 borane Inorganic materials 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 description 9
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 235000011089 carbon dioxide Nutrition 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 150000002739 metals Chemical class 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 150000001414 amino alcohols Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- IALYUOSURKZWLR-SFTDATJTSA-N (1s,2s)-2-diphenylphosphanyl-2,3-dihydro-1h-inden-1-amine Chemical compound C=1C=CC=CC=1P([C@@H]1[C@H](C2=CC=CC=C2C1)N)C1=CC=CC=C1 IALYUOSURKZWLR-SFTDATJTSA-N 0.000 description 3
- GBMBLXQWVALWHS-UHFFFAOYSA-N 1h-phosphepine Chemical compound P1C=CC=CC=C1 GBMBLXQWVALWHS-UHFFFAOYSA-N 0.000 description 3
- PKAUJJPTOIWMDM-UHFFFAOYSA-N 3h-dioxaphosphepine Chemical compound C=1C=CPOOC=1 PKAUJJPTOIWMDM-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960004424 carbon dioxide Drugs 0.000 description 3
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 3
- 239000012973 diazabicyclooctane Substances 0.000 description 3
- 229960002179 ephedrine Drugs 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- JWZAIGGNEGTDMG-UTKZUKDTSA-N (1r,2r)-1-diphenylphosphanyl-1-phenylpropan-2-amine Chemical compound C=1C=CC=CC=1P([C@@H]([C@H](N)C)C=1C=CC=CC=1)C1=CC=CC=C1 JWZAIGGNEGTDMG-UTKZUKDTSA-N 0.000 description 2
- IALYUOSURKZWLR-NHCUHLMSSA-N (1r,2r)-2-diphenylphosphanyl-2,3-dihydro-1h-inden-1-amine Chemical compound C=1C=CC=CC=1P([C@H]1[C@@H](C2=CC=CC=C2C1)N)C1=CC=CC=C1 IALYUOSURKZWLR-NHCUHLMSSA-N 0.000 description 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 2
- YDZYREHHCRHTRZ-UHFFFAOYSA-N 4-methylbenzenesulfonyl iodide Chemical class CC1=CC=C(S(I)(=O)=O)C=C1 YDZYREHHCRHTRZ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229910019891 RuCl3 Inorganic materials 0.000 description 2
- 229910006124 SOCl2 Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000007344 nucleophilic reaction Methods 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- FCLYZQXPJKJTDR-UHFFFAOYSA-N potassium;diphenylphosphanide Chemical compound C=1C=CC=CC=1P([K])C1=CC=CC=C1 FCLYZQXPJKJTDR-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000008648 triflates Chemical class 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- JWZAIGGNEGTDMG-LAUBAEHRSA-N (1s,2s)-1-diphenylphosphanyl-1-phenylpropan-2-amine Chemical compound C=1C=CC=CC=1P([C@H]([C@@H](N)C)C=1C=CC=CC=1)C1=CC=CC=C1 JWZAIGGNEGTDMG-LAUBAEHRSA-N 0.000 description 1
- WZBUXBHCACMRLB-LAUBAEHRSA-N (1s,2s)-2-diphenylphosphanyl-1-phenylpropan-1-amine Chemical compound C1([C@H](N)[C@H](C)P(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 WZBUXBHCACMRLB-LAUBAEHRSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- QUVUVMRUSAKOPB-UHFFFAOYSA-N 2-di(propan-2-yl)phosphanylethanamine Chemical compound CC(C)P(C(C)C)CCN QUVUVMRUSAKOPB-UHFFFAOYSA-N 0.000 description 1
- RXEPBCWNHKZECN-UHFFFAOYSA-N 2-diphenylphosphanylethanamine Chemical compound C=1C=CC=CC=1P(CCN)C1=CC=CC=C1 RXEPBCWNHKZECN-UHFFFAOYSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C)(C)OC(N[C@@](*)CP1(*)Cc(ccc2c3cccc2)c3-c2c(cccc3)c3ccc2C1)=O Chemical compound CC(C)(C)OC(N[C@@](*)CP1(*)Cc(ccc2c3cccc2)c3-c2c(cccc3)c3ccc2C1)=O 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- MIPGTOGPLXZBQX-CLJLJLNGSA-N N[C@@H]([C@@H](c1ccccc1)P(c1ccccc1)c1ccccc1)c1ccccc1 Chemical compound N[C@@H]([C@@H](c1ccccc1)P(c1ccccc1)c1ccccc1)c1ccccc1 MIPGTOGPLXZBQX-CLJLJLNGSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- WPJHAAGNSZRDPC-UHFFFAOYSA-N [Ru].PN Chemical class [Ru].PN WPJHAAGNSZRDPC-UHFFFAOYSA-N 0.000 description 1
- 229910052768 actinide Inorganic materials 0.000 description 1
- 150000001255 actinides Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- YGXMUPKIEHNBNQ-UHFFFAOYSA-J benzene;ruthenium(2+);tetrachloride Chemical compound Cl[Ru]Cl.Cl[Ru]Cl.C1=CC=CC=C1.C1=CC=CC=C1 YGXMUPKIEHNBNQ-UHFFFAOYSA-J 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- JZPDBTOWHLZQFC-UHFFFAOYSA-N chloro-di(propan-2-yl)phosphane Chemical compound CC(C)P(Cl)C(C)C JZPDBTOWHLZQFC-UHFFFAOYSA-N 0.000 description 1
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- IWRBGJKCDORZHK-OAHLLOKOSA-N diphenyl-[[(2r)-pyrrolidin-2-yl]methyl]phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C[C@H]1CCCN1 IWRBGJKCDORZHK-OAHLLOKOSA-N 0.000 description 1
- IWRBGJKCDORZHK-HNNXBMFYSA-N diphenyl-[[(2s)-pyrrolidin-2-yl]methyl]phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C[C@@H]1CCCN1 IWRBGJKCDORZHK-HNNXBMFYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- MCRSZLVSRGTMIH-UHFFFAOYSA-N ditert-butyl(chloro)phosphane Chemical compound CC(C)(C)P(Cl)C(C)(C)C MCRSZLVSRGTMIH-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004636 glovebox technique Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- UBEJJZQIWCNBQU-ZYHUDNBSSA-N tert-butyl n-[(1s,2r)-2-hydroxy-1-phenylpropyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]([C@H](O)C)C1=CC=CC=C1 UBEJJZQIWCNBQU-ZYHUDNBSSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07F9/6568—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 atoms as the only ring hetero atoms
- C07F9/65683—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 atoms as the only ring hetero atoms the ring phosphorus atom being part of a phosphine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2419—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising P as ring member
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2495—Ligands comprising a phosphine-P atom and one or more further complexing phosphorus atoms covered by groups B01J31/1845 - B01J31/1885, e.g. phosphine/phosphinate or phospholyl/phosphonate ligands
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5004—Acyclic saturated phosphines
-
- 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
- C07F9/657163—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 the ring phosphorus atom being bound to at least one carbon atom
- C07F9/65719—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 the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonous acid derivative
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
-
- 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
- B01J2531/821—Ruthenium
Definitions
- TITLE METHOD FOR THE PREPARATION OF AMINOPHOSPHINE
- the present disclosure relates to a general procedure for the synthesis of a wide range of achiral and chiral aminophosphine ligands, and their use for the preparation of chiral and achiral metal aminophosphine catalysts, for example, for the hydrogenation of ketones, aldehydes and imines.
- Catalytic hydrogenation is a fundamental reaction in chemistry, and is used in a large number of chemical processes. Catalytic hydrogenation of ketones and aldehydes are useful and indispensable processes for the synthesis of alcohols, which are valuable end products and precursor chemicals in the pharmaceutical, agrochemical, flavor, fragrance, material and fine chemical industries. 1
- molecular hydrogen (H 2 ) is used. However, for the hydrogenation process to proceed, a catalyst or catalytic system is needed to activate the molecular hydrogen.
- Noyori and co-workers developed the versatile RuCl 2 (PR 3 ) 2 (diamine) and RuCl 2 (diphosphine)(diamine) hydrogenation catalyst system that are highly effective for the hydrogenation of ketones. 2 It was subsequently discovered that the Noyori catalysts were effective for the reductive hydrogenation of imines to amines. 3
- RuCl 2 (aminophosphine)2 and RuCl 2 (diphosphine)(aminophosphine) are also very effective catalysts for the hydrogenation of ketones, aldehydes and imines, including the preparation of chiral compounds. 4 Hence, these catalysts are versatile alternatives to the Noyori-type catalysts.
- the present disclosure includes a method for preparing aminophosphine ligands comprising reacting a compound of the formula I
- LG 1 is a suitable leaving group; q is 0 or 1 ; p is 1 or 2, where when p is 1, the N atom is further linked to R 7 or any one of R 1 , R 2 , R 3 , R 4 , R 5 R 6 or LG, and when N is linked to any one of R 1 , R 2 , R 3 , R 4 , R 5 R 6 or LG, or if p is 2, q is 0; n is O, 1, 2, 3 or 4; PG is a suitable amine protecting group and, when p is 2, PG is the same or different; Y is a cation;
- R 1 to R 6 are simultaneously or independently selected from H, Ci -2O alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R 7 is selected from d ⁇ alkyl and aryl, said latter two groups being optionally substituted;
- R and R are simultaneously or independently selected from H, C 1-20 alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 10 and N(R I0 ) 2 , said latter 7 groups being optionally substituted, or R 8 and R 9 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R and R 9 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl;
- R 10 is selected from Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of halo, OH, NH 2 , OR 1 1 , N(R ⁇ ) 2 and R n ; and
- R 11 is selected from Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted.
- the present disclosure includes a method for preparing aminophosphine ligands comprising reacting a compound of the formula II
- one of q and r is 1 , while the other is 0; n is 0, 1, 2, 3 or 4;
- R 1 to R 6 are simultaneously or independently selected from H, Ci -2 oalkyl, C 2- 2 oalkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R 7 is selected from Ci -6 alkyl and aryl, said latter two groups being optionally substituted; R and R are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 10 and N(R 10 ) 2 , said latter 7 groups being optionally substituted, or R 8 and R 9 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 8 and R 9 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S.
- R 10 is selected from Ci -6 alkyl, C 2-6 alkenyl, C 2 . 6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of halo, OH, NH 2 , OR 11 , N(R ⁇ ) 2 and R ⁇ ; and R 11 is selected from Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; and
- R 12 and R 13 are simultaneously or independently selected from H, Ci. 2 oalkyl, C 2- 20 alkenyl, C 2-2 oalkynyl, aryl, heteroaryl, OR 10 and N(R 10 ) 2 , said latter 7 groups being optionally substituted, or R 12 and R 13 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 12 and R 13 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NC 1-6 alkyl.
- aminophosphine ligands are complexed with a metal to form aminophosphine metal catalysts.
- aminophosphine metal catalysts are useful for the hydrogenation of ketones, aldehydes and imines.
- R 14 and R 15 are simultaneously or independently selected from H, C 1-20 alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted;
- R 16 is selected from H, Ci -6 alkyl and aryl, said latter two groups being optionally substituted or R 16 is PR 19 R 20 ; or two of R 14 , R 15 and R 16 are linked to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R and R are linked together with the phosphorous atom to which said R and R groups are linked to form an optionally substituted polycyclic ring of the formula
- R 19 and R 20 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 2 oalkenyl, C 2-2 oalkynyl, aryl, heteroaryl, OR 21 and N(R 2 ') 2 , said latter 7 groups being optionally substituted, or R 19 and R 20 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 19 and R 20 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl; the optional substituents are selected from one or more of halo, OH,
- R 23 and R 24 are simultaneously or independently selected from H, Ci -6 alkyl and aryl, said latter two groups being optionally substituted or one of R 23 and R 24 is PR 28 R 29 ;
- R 25 and R 26 are simultaneously or independently selected from H, Ci -2 oalkyl, C 2- 2O alkenyl, C 2-2 oalkynyl, aryl, heteroaryl, OR 30 and N(R 30 ) 2 , said latter 7 groups being optionally substituted, or R 25 and R 26 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 25 and R 26 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NC 1-6 alkyl;
- R 27 represents optional substituents selected from one or more of OH
- R 28 and R 29 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 2 oalkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 32 and N(R 32 ) 2 , said latter 7 groups being optionally substituted, or R 28 and R 29 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 28 and R 29 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl; R 30 , R 31 and R 32 are independently selected from Ci -6 alkyl, C 2-6 alkenyl, C ⁇ alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of
- R 33 is selected from Ci- ⁇ alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted.
- metal complexes suitably a transition metal complex comprising a ligand of the formula II, IV, V, VI or VII.
- Figure 1 is a schematic showing the method of producing an aminophosphine ligand in accordance with one embodiment of the disclosure
- Figure 2 is a schematic showing the method of producing an aminophosphine ligand in accordance with an embodiment of the disclosure
- Figure 3 is a schematic showing the method of producing an aminophosphine ligand in accordance with an embodiment of the disclosure.
- Ci -n alkyl as used herein means straight and/or branched chain, saturated alkyl groups containing from one to "n" carbon atoms and includes
- n (depending on the identity of n) methyl, ethyl, propyl, isopropyl, n-butyl, s-butyl, isobutyl, t-butyl, 2,2-dimethylbutyl, n-pentyl, 2-methylpentyl, 3-methylpentyl, 4- methylpentyl, n-hexyl and the like, where the variable n is an integer representing the largest number of carbon atoms in the alkyl radical.
- C 2-n alkenyl as used herein means straight and/or branched chain, unsaturated alkyl groups containing from one to n carbon atoms and one to three double bonds, and includes (depending on the identity of n) vinyl, allyl, 2- methylprop-1-enyl, but-1-enyl, but-2-enyl, but-3-enyl, 2-methylbut-l-enyl, 2- methylpent-1-enyl, 4-methylpent-l-enyl, 4-methylpent-2-enyl, 2-methylpent-2-enyl, 4-methylpenta-l,3-dienyl, hexen-1-yl and the like, where the variable n is an integer representing the largest number of carbon atoms in the alkenyl radical.
- C 2-n alkynyl as used herein means straight and/or branched chain, unsaturated alkyl groups containing from one to n carbon atoms and one to three triple bonds, and includes (depending on the identity of n) ethynyl, 1-propynyl, 2- propynyl, 2-methylprop-l-ynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1,3-butadiynyl, 3- methylbut-1-ynyl, 4-methylbut-ynyl, 4-methylbut-2-ynyl, 2-methylbut-l-ynyl, 1- pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1,3-pentadiynyl, 1 ,4-pentadiynyl, 3- methylpent-1-ynyl, 4-methylpent-2-ynyl4-methyl
- C 3-2 ocycloalkyl as used herein means a monocyclic or polycyclic saturated carbocylic group containing from three to twenty carbon atoms and includes cyclopropyl, cyclobutyl, cyclopentyl, cyclodecyl and the like.
- aryl as used herein means a monocyclic or polycyclic aromatic ring system containing from 6 to 14 carbon atoms and at least one aromatic group and includes phenyl, naphthyl, anthracenyl, 1 ,2-dihydronaphthyl, 1,2,3,4- tetrahydronaphthyl, fluorenyl, indanyl, indenyl, ferrocenyl and the like.
- heteroaryl as used herein means a monocyclic or polycyclic ring system containing one or two aromatic rings and from 5 to 14 atoms of which, unless otherwise specified, one, two, three, four or five are heteromoieties independently selected from N. NH, N(Ci. 6 alkyl), O and S and includes thienyl, furyl, pyrrolyl, pyrididyl, indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, benzothienyl and the like.
- ring system refers to any type of cyclic structure that comprises one or more rings and any type of saturation and optionally includes, where indicated, heteromoieties or metals. Ring systems formed between two R groups or an R group and a heteroatom, include within the system the atoms to which the R groups and/or heteroatoms are attached and any atoms linking the atoms to which the R groups and/or heteroatoms are attached.
- fluoro- substituted with respect to any specified group as used herein means that the one or more, including all, of the hydrogen atoms in the group have been replaced with a fluorine, and includes trifluoromethyl, pentafluoroethyl, fluoromethyl and the like.
- halo as used herein means halogen and includes chloro, flouro, bromo and iodo.
- a method for preparing aminophosphine ligands comprising reacting a compound of the formula I )p
- LG 1 is a suitable leaving group; q is O or l; p is 1 or 2, where when p is 1, the N atom is further linked to R 7 or any one of R 1 , R 2 ,
- R 3 , R 4 , R 5 R 6 or LG when N is linked to any one of R 1 , R 2 , R 3 , R 4 , R 5 R 6 or LG, or if p is 2, q is 0; n is O, 1, 2, 3 or 4; PG is a suitable amine protecting group and, when p is 2, PG is the same or different;
- Y is a cation
- R 1 to R 6 are simultaneously or independently selected from H, Ci -20 alkyl, C 2-
- alkenyl, C 2-2 oalkynyl, C 3-2 ocycloalkyl, aryl and heteroaryl said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R 7 is selected from Ci -6 alkyl and aryl, said latter two groups being optionally substituted;
- R 8 and R 9 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 10 and N(R 10 ) 2 , said latter 7 groups being optionally substituted, or R 8 and R 9 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 8 and R 9 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl;
- R 10 is selected from Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of halo, OH, NH 2 , OR 11 ,
- R 11 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted.
- R 1 to R 6 are simultaneously or independently selected from H, Ci.i O alkyl, C 2- i 0 alkenyl, C 2- i 0 alkynyl, C 3- iocycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metallated, saturated, unsaturated and/or aromatic ring system having 5 or more atoms.
- R 1 to R 6 are simultaneously or independently selected from H, d ⁇ alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the carbons to which these groups are attached and/or the nitrogen atom of the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metallated, saturated, unsaturated and/or aromatic ring system having 5 or more atoms.
- R 1 to R 6 are simultaneously or independently selected from H, methyl, phenyl, or two adjacent or geminal groups and the carbons to which said groups are attached and/or the nitrogen atom of the amino group, are linked together to form phenyl, indanyl or ferrocenyl, or a pyrrolidinyl ring.
- n is equal to 0, 1 or 2. In further embodiments of the disclosure, n is 0 or 1. In other embodiments of the present disclosure, R 7 is Ci -4 alkyl or phenyl, said latter two groups being optionally substituted. In another embodiment, R 7 is methyl.
- R 8 and R 9 are simultaneously or independently selected from H, Ci.i O alkyl, C 2- i 0 alkenyl, C- 2- ioalkynyl and aryl, said latter 4 groups being optionally substituted, or R and R are linked together to form an optionally substituted monocyclic or polycyclic ring system having 4 or more atoms, including the phosphorous atom to which R 8 and R 9 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, N, NH and NCi -6 alkyl.
- R 8 and R 9 are simultaneously or independently selected from H, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, and naphthyl, said latter 5 groups being optionally substituted, or R 8 and R 9 are linked to form an optionally substituted monocylic, fused bicylic, fused tricyclic, fused quadracyclic or fused pentacyclic ring system having 4-23 atoms, including the phosphorous atom to which R 8 and R 9 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, N, NH and NCi -6 alkyl.
- R 8 and R 9 are simultaneously Ci -6 alkyl or phenyl, in particular, methyl, ethyl, propyl, isopropyl, t-butyl, sec-butyl or phenyl. In further embodiments, R 8 and R 9 are simultaneously or independently isopropyl, t- butyl, or phenyl.
- R 8 and R 9 are linked to form an optionally substituted fused pentacyclic ring system having 23 atoms, including the phosphorous atom to which R 8 and R 9 are linked.
- R 10 is selected from C 2-4 alkenyl and phenyl, said latter 3 groups being optionally fluoro-substituted. In an embodiment, R 10 is selected from methyl and phenyl, said latter 2 groups being optionally fluoro-substituted.
- the optional substituents are selected from one or more of halo, OH, NH 2> OR 1 1 , N(R U ) 2 and R 11 , in which R 11 is selected from Ci -4 alkyl, C 2-4 alkenyl and phenyl, said latter 3 groups being optionally fluoro-substituted.
- R 11 is selected from methyl and phenyl, said latter 2 groups being optionally fluoro-substituted.
- PG means a suitable protecting group.
- suitable protecting group would be understood by a person skilled in the art to means any moiety that, when linked to the amine functional group, prevents the amine functionality from participating in unwanted side reactions and which can be readily removed under conditions that do not degrade, decompose or otherwise interfere with the process of the disclosure to lower the yield and purity of the compounds of formula II.
- suitable protecting groups would be well within the abilities of a person skilled in the art. For example, a person skilled in the art may refer to "Protective Groups in Organic Chemistry” McOmie, J.F.W. Ed., Plenum Press, 1973 and in Greene, T. W.
- protecting groups include, but are not limited to trimethylsilyl (TMS), acetyl, tert- butyldimethylsilyl (TBDMS), tert-butoxycarbonyl (BOC), benzyloxycarbonyl, 9- fluorenylmethyloxycarbonyl (FMOC), benzyl and the like.
- LG 1 means “leaving group”.
- suitable leaving group as it applies to LG 1 would be understood by a person skilled in the art to mean any group attached to an atom that can be displaced by the nucleophilic phosphorus atom of the metal phosphide reagent under the conditions of the method of the disclosure.
- Suitable leaving groups for LG 1 include, but are not limited to, halides, including chloro, bromo, and iodo, tosylates, mesylates, and triflates and the like.
- LG 1 is a cyclic leaving group that is linked to another atom in the compound of formula I, including the nitrogen atom of the amine.
- a portion of the leaving group remains linked to the other atom of the compound of formula I after nucleophilic displacement by the metal phosphide reagent, and those remaining portions may be removed, for example, during removal of the PG, to provide compounds of formula II.
- a cyclic leaving group includes cyclic sulfamidates that are formed between the amine nitrogen and the carbon to which the LG is attached.
- Y is any suitable cation, for example any metal that can complex with a nucleophilic phosphide reagent.
- metals include the alkaline metals, for example lithium, sodium, potassium and the like, the alkaline earth metals. Suitable metals are the alkaline metals lithium, sodium and potassium.
- Y is Li or K.
- p is 1 or 2, where when p is 1, the N atom is further linked to R 7 or any one of R 1 , R 2 , R 3 , R 4 , R 5 R 6 or LG 1 , and when N is linked to any one of R 1 , R 2 , R 3 , R 4 , R 5 R 6 or LG 1 , or if p is 2, q is 0.
- p is 1 when a cyclic leaving group is used.
- p is 2 and the protecting group can be the same or different.
- the conditions to provide a compound of the formula II are nucleophilic reaction conditions that would be known to a person skilled in the art.
- the conditions to provide a compound of formula II comprise adding a compound of the formula I to a metal phosphide reagent of the formula Y-PR 8 R 9 , at a temperature of about -50 0 C to about 0 0 C over a period of about 1 hour to about 4 hours.
- the solution of a compound of the formula I and a metal phosphide reagent of the formula Y-PR 8 R 9 is stirred at a temperature of about 10 0 C to about 70 0 C for a period of about 2 to about 24 hours.
- the conditions, including time and temperature may be varied, depending, for example, on the structure of the compound of formula I and the metal phosphide reagent.
- the conditions to provide a compound of the formula II comprise the reaction between the compound of the formula I and the metal phosphide reagent under anhydrous conditions and in an inert atmosphere (e.g. in the absence of oxygen).
- the conditions to provide a compound of the formula II comprise the reaction between a compound of the formula I and a metal phosphide reagent in an aprotic solvent.
- the reaction between a compound of the formula I and a metal phosphide reagent is performed in a polar, aprotic solvent.
- the reaction between a compound of the formula I and a metal phosphide reagent is performed in a variety of solvents, including ethers such as tetrahydrofuran or diethyl ether, acetonitrile, benzene, toluene, hexanes, dimethyformamide and the like.
- the reaction between a compound of the formula I and a metal phosphide reagent is performed in tetrahydrofuran.
- the compounds of formula I are commercially available or may be prepared using methods known in the art.
- compounds of formula I may be prepared from the corresponding amino alcohols.
- Methods for attaching protecting groups onto amino groups are known in the art, in particular in the presence of a hydroxyl group or a latent or protected hydroxyl group (see for example, "Protective Groups in Organic Chemistry” McOmie, J.F.W. Ed., Plenum Press, 1973 and in Greene, T. W. and Wuts, P. G. M., "Protective Groups in Organic Synthesis", John Wiley & Sons, 3 rd Edition, 1999).
- amino alcohols may be converted into a compound of formula I comprising a cyclic sulfamidate leaving group by first monoprotecting the amine nitrogen with any suitable PG, for example, t- butoxycarbonyl (t-BOC), followed by reaction of the resulting derivative according to the procedure described by Qin et al. (J. Org. Chem.
- the metal phosphide reagents are either commercially available or may be prepared using methods known in the art as described hereinbelow. Typically the metal phosphide reagent is prepared in situ by reacting the corresponding phosphine, Z-PR 8 R 9 , where Z is for example, H or Cl, or the corresponding phosphepine borane, with a strong base, for example an alkyl lithium or lithium metal, at reduced temperatures, for example at about -80 0 C to about 10 0 C. In another embodiment, the method further comprises the step of reacting a compound of formula II as defined above, with a compound of the formula III
- R 12 and R 13 are as defined for R 8 and R 9 in formula II and R 1 - R 9 are as defined in formula II, LG 2 is a suitable leaving group, and one of q and r is 1, while the other of q and r is 0.
- R 12 and R 13 are simultaneously or independently selected from H, Ci-ioalkyl, C 2- i 0 alkenyl, C- 2- ioalkynyl and aryl, said latter 4 groups being optionally substituted, or R 12 and R 13 are linked together to form an optionally substituted monocyclic or polycyclic ring system having 4 or more atoms, including the phosphorous atom to which R 12 and R 13 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, N, NH and NCi -6 alkyl.
- R 12 and R 13 are simultaneously or independently selected from H, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, and naphthyl, said latter 5 groups being optionally substituted, or R 12 and R 13 are linked to form an optionally substituted monocytic, fused bicylic, fused tricyclic, fused quadracyclic, fused pentacyclic, fused hexacyclic or fused heptacyclic ring system having 4-32 atoms, including the phosphorous atom to which R 12 and R 13 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteroatom selected from O, N, NH and NCi_ 6 alkyl.
- the compound of formula III is
- LG 2 is a suitable leaving group
- a method for preparing aminophosphine ligands comprising reacting a compound of the formula II
- LG 2 is a suitable leaving group; one of q and r is 1, while the other is 0; n is 0, 1, 2, 3 or 4;
- R 1 to R 6 are simultaneously or independently selected from H, Ci -2 oalkyl, C 2- 20 alkenyl, C 2-20 alkynyl, C 3-20 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R 7 is selected from Ci -6 alkyl and aryl, said latter two groups being optionally substituted;
- R 8 and R 9 are simultaneously or independently selected from H, Ci- 20 alkyl, C 2 . 20 alkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 10 and N(R 10 ) 2 , said latter 7 groups being optionally substituted, or R 8 and R 9 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 8 and R 9 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NC )-6 alkyl;
- R 10 is selected from C h alky!, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of halo, OH, NH 2 , OR 11 ,
- R 11 is selected from C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted;
- R 12 and R 13 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 2 oalkenyl, C 2-2 oalkynyl, aryl, heteroaryl, OR 10 and N(R 1 °) 2 , said latter 7 groups being optionally substituted, or R 12 and R 13 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 12 and R 13 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NC 1-6 alkyl.
- R 1 to R 6 are simultaneously or independently selected from H, Ci.ioalkyl, C 2- ioalkenyl, C 2- ioalkynyl, C 3 .i 0 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted, or two adjacent or geminal groups, including the nitrogen atom of the amino group, are linked together to form an optionally substituted monocyclic or polycyclic, metallated, saturated, unsaturated and/or aromatic ring system having 5 or more atoms.
- R 1 to R 6 are simultaneously or independently selected from H, Ci -4 alkyl, C 2-4 alkenyl, C 2 .
- R 1 to R 6 are simultaneously or independently selected from H, methyl, or phenyl, or two adjacent or geminal groups, are linked together with the carbons to which said groups are attached, and/or with the nitrogen atom of the amino group, to form a phenyl, indanyl or ferrocenyl ring.
- n is equal to 0, 1 or 2. In a further embodiment, n is equal to 0 or 1.
- R 7 is selected from or phenyl, said latter two groups being optionally substituted. In another embodiment, R 7 is methyl.
- R and R are simultaneously or independently selected from H, Ci.i O alkyl, C 2- i 0 alkenyl, C- 2- ioalkynyl and aryl, said latter 4 groups being optionally substituted, or R 8 and R 9 are linked together to form an optionally substituted monocyclic or polycyclic ring system having 4 or more atoms, including the phosphorous atom to which R 8 and R 9 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, N, NH and
- R 8 and R 9 are simultaneously or independently selected from H, Ci ⁇ alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, and naphthyl, said latter 5 groups being optionally substituted, or R 8 and R 9 are linked to form an optionally substituted monocylic, fuse
- R 8 and R 9 are simultaneously or independently isopropyl, t-butyl, or phenyl.
- R 8 and R 9 are linked to form an optionally substituted fused pentacyclic ring system having 23 atoms, including the phosphorous atom to which R 8 and R 9 are linked.
- the fused pentacyclic ring system is
- R 10 is selected from Ci -4 alkyl, C 2-4 alkenyl and phenyl, said latter 3 groups being optionally fluoro-substituted. In an embodiment, R 10 is selected from methyl and phenyl, said latter 2 groups being optionally fluoro- substituted.
- the optional substituents are selected from one or more of halo, OH, NH 2, OR 11 , N(R U ) 2 and R 11 , in which R 1 1 is selected from the group consisting of Ci-4alkyl, C 2-4 alkenyl and phenyl, said latter 3 groups being optionally fluoro-substituted.
- R 11 is selected from methyl and phenyl, said latter 2 groups being optionally fluoro-substituted.
- R 12 and R 13 are simultaneously or independently selected from H, Ci -10 alkyl, C 2 -i 0 alkenyl, C- 2- ioalkynyl and aryl, said latter 4 groups being optionally substituted, or R 12 and R 13 are linked together to form an optionally substituted monocyclic or polycyclic ring system having 4 or more atoms, including the phosphorous atom to which R 11 and R 12 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, N, NH and NCi. 6 alkyl.
- R 12 and R 13 are simultaneously or independently selected from H, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, and naphthyl, said latter 5 groups being optionally substituted, or R 12 and R 13 are linked to form an optionally substituted monocylic, fused bicylic, fused tricyclic, fused quadracyclic, fused pentacyclic, fused hexacyclic or fused heptacyclic ring system having 4-32 atoms, including the phosphorous atom to which R 12 and R 13 are linked, in which the rings are saturated, unsaturated and/or aromatic and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteroatom selected from O, N, NH and NCi -6 alkyl.
- the compound of formula III is
- LG 2 in a compound of formula III is a suiable leaving group.
- suitable leaving group in a compound of formula III would be understood by a person skilled in the art to mean any group attached to a phosphorous atom that can be displaced by the nucleophilic nitrogen atom of the compound of formula II.
- Suitable leaving groups include, but are not limited to, halides, including chloro, bromo, and iodo, tosylates, mesylates, and triflates and the like.
- the conditions to provide a compound of the formula IV are nucleophilic reaction conditions that would be known to a person skilled in the art.
- the conditions to provide a compound of formula IV comprise adding a compound of the formula III to a compound of the formula II at about room temperature.
- the solution of a compound of the formula II and formula III is stirred at about room temperature for a period of about 2 to about 24 hours.
- the conditions, including time and temperature may be varied, depending, for example, on the structure of the compounds of formula II and formula III.
- the conditions to provide a compound of the IV comprise the reaction between the compound of the formula II and a compound of formula III under anhydrous conditions and in an inert atmosphere (e.g. in the absence of oxygen).
- the conditions to provide a compound of the formula IV comprise the reaction between a compound of the formula II and a compound of the formula III in an aprotic solvent.
- the reaction between a compound of the formula II and a compound of the formula III is performed in a polar, aprotic solvent.
- the reaction between a compound of the formula II and a compound of the formula III is performed in a variety of solvents, including chlorinated solvents such as dichloromethane, ethers such as tetrahydrofuran or diethyl ether, acetonitrile, benzene, toluene, hexanes, dimethyformamide and the like.
- the reaction between a compound of the formula II and a compound of the formula III is performed in dichloromethane.
- the aminophosphine ligands prepared using the method of the present disclosure are complexed with any metal for use as catalysts.
- the metal is any transition metal of groups 3 through 12 of the periodic table, suitably groups 4 through 10, plus the lanthanides and actinides. Examples of suitable metals include, but are not limited to Co, Rh, Ir, Ru, Os and Re.
- the metal is Ru.
- the aminophosphine ligands of formula II are complexed with an RuCl 2 group to form RuCl 2 (aminophosphine) 2 and RuCl 2 (diphosphine)(aminophosphine) catalysts.
- the aminophospine metal catalysts are those useful for the hydrogenation of ketones, aldehydes and imines.
- R 14 and R 15 are simultaneously or independently selected from H, Ci -2 oalkyl, C 2 .
- R 16 is selected from H, and aryl, said latter two groups being optionally substituted or R 16 is PR 19 R 20 ; or two of R 14 , R 15 and R 16 are linked to form an optionally substituted monocyclic or polycyclic, metalated, saturated, unsaturated and/or aromatic ring system having 3 or more atoms;
- R 17 and R 18 are linked together with the phosphorous atom to which said R 17 and R 18 groups are linked to form an optionally substituted polycyclic ring of the formula
- R 19 and R 20 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 2 oalkenyl, C2 -20 alkynyl, aryl, heteroaryl, OR 21 and N(R 21 ) 2 , said latter 7 groups being optionally substituted, or R 19 and R 20 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 19 and R 20 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NC 1-6 alkyl; the optional substituents are selected from one or more of halo, OH, NH 2
- R 14 and R 15 are simultaneously or independently selected from H, Ci -10 alkyl, C 2- ioalkenyl, C 2- i 0 alkynyl, C 3- iocycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted.
- R 14 and R 15 are simultaneously or independently selected from H, Ci- 4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, aryl and heteroaryl, said latter 6 groups being optionally substituted.
- R 14 and R 15 are simultaneously or independently selected from H, methyl, or phenyl.
- R 16 is H, Ci -4 alkyl or phenyl, said latter two groups being optionally substituted. In a further embodiment, R 16 is H or methyl.
- R 16 is PR 19 R 20 , where R 19 and R 20 are simultaneously or independently selected from H, Ci.i O alkyl, C 2- i 0 alkenyl, C 2- l oalkynyl, aryl, heteroaryl, OR 21 and N(R 21 ) 2 , said latter 7 groups being optionally substituted, or R 19 and R 20 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 5 to 23 atoms, including the phosphorous atom to which said R 19 and R 20 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -4 alkyl.
- R 19 and R 20 are simultaneously or independently selected from H, Ci -6 alkyl, phenyl and OR 21 , said latter 3 groups being optionally substituted, or R 19 and R 20 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 5 to 23 atoms, including the phosphorous atom to which said R 19 and R 20 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with O.
- R 16 is selected from:
- R 14 , R 15 and R 16 are linked to form an optionally substituted monocyclic, bicyclic, tricyclic, saturated, unsaturated and/or aromatic ring system having 5 to 14 atoms.
- R 15 and R 16 are linked to form an optionally substituted monocyclic or bicyclic, saturated, and/or aromatic ring system having 5 to 10 atoms.
- the optional substituents on the compounds of formula V are selected from one or more of Cl, F, OR 22 and N(R 22 ) 2 and R 22 , where R 22 is selected from Ci -6 alkyl, and phenyl, said latter 4 groups being optionally fluoro-substituted.
- the optional substituents on the compounds of formula V are selected from one or more of CH 3 , CF 3 , OCH 3 , and OCF 3 .
- R 23 and R 24 are simultaneously or independently selected from H, Ci -6 alkyl and aryl, said latter two groups being optionally substituted or one of R 23 and R 24 is PR 28 R 29 ;
- R 25 and R 26 are simultaneously or independently selected from H, Ci -2 oalkyl, C 2- 20 alkenyl, C 2-2 oalkynyl, aryl, heteroaryl, OR 30 and N(R 30 ) 2 , said latter 7 groups being optionally substituted, or R 25 and R 26 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 25 and R 26 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl;
- R 27 represents optional substituents selected from one or more of OH
- R 28 and R 29 are simultaneously or independently selected from H, Ci -20 alkyl, C 2- 20 alkenyl, C 2-20 alkynyl, aryl, heteroaryl, OR 32 and N(R 32 ) 2 , said latter 7 groups being optionally substituted, or R 28 and R 29 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 4 or more atoms, including the phosphorous atom to which said R 28 and R 29 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl; R 30 , R 31 and R 32 are independently selected from Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted; the optional substituents are selected from one or more of
- R 33 is selected from Ci ⁇ alkyl, C 2-6 alkenyl, C 2-6 alkynyl and aryl, said latter 4 groups being optionally fluoro-substituted.
- R 23 and R 24 are simultaneously or independently selected from H, Ci -4 alkyl, phenyl and naphthyl.
- R 23 and R 24 are simultaneously or independently selected from H, methyl and phenyl.
- R 23 and R 24 are simultaneously selected from H, methyl and phenyl.
- one of R 23 and R 24 is PR 28 R 29 and R 28 and R 29 are simultaneously or independently selected from H, Ci.
- R 28 and R 29 are simultaneously or independently selected from H, Ci -6 alkyl, phenyl and OR 32 , said latter 3 groups being optionally substituted, or R 28 and R 29 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 5 to 23 atoms, including the phosphorous atom to which said R 28 and R 29 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with O.
- PR 28 R 29 is selected from:
- R 25 and R 26 are simultaneously or independently selected from H, Ci-ioalkyl, C 2- i 0 alkenyl, C 2- l oalkynyl, aryl, heteroaryl, OR 30 and N(R 30 ) 2 , said latter 7 groups being optionally substituted, or R 25 and R 26 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 5 or more atoms, including the phosphorous atom to which said R 25 and R 26 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with a heteromoiety selected from O, S, N, NH and NCi -6 alkyl.
- R 25 and R 26 are simultaneously or independently selected from H, Ci -6 alkyl, phenyl and OR 30 , said latter 3 groups being optionally substituted, or R 25 and R 26 are linked together to form an optionally substituted monocyclic or polycylic, saturated, unsaturated and/or aromatic ring system having 5 to 23 atoms, including the phosphorous atom to which said R 25 and R 26 groups are linked, and in which one or more carbon atoms in said monocyclic or polycyclic ring system are optionally replaced with O.
- R 27 represents optional substituents selected from one or five of OR 31 , N(R 31 ⁇ and R 31 is independently selected from Ci- 4 alkyl and phenyl, said latter 2 groups being optionally fluoro-substituted. In a further embodiment, R 27 is H.
- R 30 and R 32 are independently selected from Ci -4 alkyl, and phenyl, said latter 2 groups being optionally fluoro- substituted.
- the optional substituents are selected from one or five of Cl, F, OR 33 , N(R 33 ) 2 and R 33 , and R 33 is selected from Ci- 4 alkyl and phenyl, said latter 2 groups being optionally fluoro-substituted.
- amino phosphine ligand of the formula V is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethy
- aminophnosphine ligand of formula VI is
- aminophosphine ligand of formula VII is
- metal complexes suitably a transition metal complex comprising a ligand of the formula II, IV, V, VI or VII.
- the transition metal complex is of the type MCl 2 (aminophosphine) 2 and MCl 2 (diphosphine)(aminophosphine), where aminophosphine is of the formula Ha, lib, Hc or Hd.
- M is Ru.
- Example 1 Preparation of aminophosphine ligands
- Example 1.1 2-(Diphenylphosphino)ethanamine
- Butyl lithium (155 ml of a 1.6 M solution in hexane) was added dropwise to a cold (O 0 C) solution of diphenylphosphine (45 g, 0.24 mole) in THF (200 ml). The mixture was stirred for 2 hours at room temperature and a solution of N,N'-bis(trimethylsilyl)- 2-chloroethanamine (54 g, 0.24 mole) added slowly at O 0 C. The mixture was refluxed for 4 hours then cooled to room temperature. Water (50 ml) was added, followed by 2.0 M H 2 SO 4 solution (200 ml).
- Example 4 General Procedures for the preparation of aminophosphine ligands from sulfamidates A solution of potassium diphenylphosphide (28 ml, 0.5 M in hexane, 14 mmol) was added slowly to a solution of the sulfamidate (12 mmol) in THF (100 ml) at -5O 0 C and the mixture was stirred at that temperature for 2h, then the mixture was slowly warmed to RT and stirred overnight. De-gassed H 2 SO 4 solution (2M, 30ml) in brine (50 ml) was added and the mixture was stirred for Ih, after which, de-gassed saturated Na 2 CO 3 solution (50 ml) was added to neutralize the acid.
- K diphenylphosphide 28 ml, 0.5 M in hexane, 14 mmol
- Butyl lithium (34 ml of a 2.5 M solution in hexane) was added to a solution of (l lbR)-4,5-dihydro-3H-dinaphtho[2,l-c:l',2'-e]phosphepine borane (28.0 g, 86 mmol) in THF (250 ml) at -78 0 C.
- the mixture was stirred at -78 0 C for 1.5 hour, and a solution of N,N'-bis(trimethylsilyl)-2-chloroethanamine (19.2 g, 86 mmol) in THF (20 ml) added.
- the reaction mixture was allowed to slowly warm to room temperature and refluxed for 24 hours.
- Tetrafluoroboric acid (HBF 41 Et 2 O, 3.4 ml) was added to the solution of 2- ((l lbR)-3H-dinaphtho[2,l-c: l',2'-e]phos ⁇ hepin-4(5H)-yl)ethanamine borane (2.0 g) in CH 2 Cl 2 (50 ml) at O 0 C. The mixture was stirred at room temperature overnight. Saturated NaHCO 3 solution (2 x 100 ml) was added and the mixture stirred for 1 hour.
- Trifloroacetic acid (30 ml) was added to the solution Of (IiS 1 , 25)- 1, 2-diphenyl-2-(S)- phosphepine ethyleneamine-N-Boc (12 g) in CH 2 Cl 2 (100 ml) at 0 0 C. The mixture was stirred at RT overnight. The volatiles were removed under vacuum and the residue was dissolved in CH 2 Cl 2 (150 ml). It was neutralized with Na 2 CO 3 (saturated, 50 ml) in brine (20 %, 100 ml). The aqueous layer was extracted with CH 2 Cl 2 (100 ml). The combined organic layer was washed with brine (20 %) and dried over MgSO 4 for 3h.
- Trifluoroacetic acid (30 ml) was added to a solution Of (I 1 S, 25)-l-methyl-2-diphenyl- 2-(S)-phosphepinoethylamine-N-Boc (10.7 g) in CH 2 Cl 2 (100 ml) at 0 0 C. The mixture was stirred at RT overnight. The volatiles were removed under vacuum and the residue was dissolved in CH 2 Cl 2 (200 ml). It was neutralized with Na 2 CO 3 (saturated, 50 ml) in brine (20 %, 100 ml). The aqueous layer was extracted with CH 2 Cl 2 (100 ml). The combined organic layer was washed with brine (20 %) and dried over MgSO 4 for 3h.
- the solvent was removed to give the crude product as a white solid (8.3 g) which was purified by filtering through a silica gel pad (eluent: CH 2 Cl 2 /hexane, 1/1, 300 ml to remove impurities, CH 2 C1 2 /THF, 9/1, 200 ml to elute the product).
- the solvent was removed from the filtrate to give the product as a colorless solid (7.2 g, yield: 82.4 %).
- Trifluoroacetic acid (3.5 ml) was added to a solution of tert-butyl-2-((l lbS)-3H- dinaphtho[2,l-c:l',2'-e]phosphepin-4(5H)-yl)ethylcarbamate (1.6 g) in CH 2 Cl 2 (30 ml) at room temperature. The mixture was stirred at RT overnight following which all volatiles were removed. The residue was dissolved in CH 2 Cl 2 (50 ml) and the solution was neutralized with Na 2 CO 3 (saturated, 50 ml) in brine (20%, 50 ml).
- Example 7 N-((lS,2S)-2-((4R,llbS)-3H-dinaphtho[2,l-c:l ⁇ 2 '-e]phosphepin-4(5H)- yl)-l, 2-diphenylethyl)-l , l-bis(3, 5-(trifluoromethylphenyl)phosphinamine
- Example 8 (HbS)-N-((lS,2S)-2-((4R, llbS)-3H-dinaphtho[2,l-c:l ⁇ 2 '-e]phosphepin- 4(5H)-yl)-l, 2-diphenylethyl)dinaphtho[2, 1 -d: 1 ', 2 '-J][1, 3, 2]dioxaphosphepin-4-amine
- Example 13 General Procedure for Preparation of new aminophosphine catalysts
- the new catalysts (S-Binap)((l S,2S)-2-(diphenylphosphino)-l ,2-diphenylethanamine) and (S-Binap)((l S,2S)-2-(Diphenylphosphino)-2,3-dihydro-lH-inden-l -amine) were prepared using the general procedure below.
- Tetrahydrofuran (20 ml) was added to a mixture of the S-binap ligand (0.5 g, 0.8 mmol) and [RuCl 2 (benzene)] 2 (200 mg, 0.4 mmol), followed by DMF (0.5 ml) and the mixture refluxed for 6 hours under argon.
- the solvent was removed under reduced pressure and a solution of the aminophosphine (0.8 mmol) in toluene 20 added.
- Ether (10 ml) was then added and the mixture stirred for 2 hours under argon.
- the solids were filtered, washed with ether and dried under vacuum.
- the catalysts were used for the hydrogenation of acetophenone without further purification.
- Example 14 Catalytic hydrogenation of acetophenone using new catalysts
- Ligand Solvent Con v. % e.e. %
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CA002689239A CA2689239A1 (en) | 2007-06-08 | 2008-06-09 | Method for the preparation of aminophosphine ligands and their use in metal catalysts |
JP2010510624A JP5466152B2 (en) | 2007-06-08 | 2008-06-09 | Process for the preparation of aminophosphine ligands and their use in metal catalysts |
EP08757212A EP2167515A4 (en) | 2007-06-08 | 2008-06-09 | Method for the preparation of aminophosphine ligands and their use in metal catalysts |
AU2008258233A AU2008258233C1 (en) | 2007-06-08 | 2008-06-09 | Method for the preparation of aminophosphine ligands and their use in metal catalysts |
US12/663,369 US8658825B2 (en) | 2007-06-08 | 2008-06-09 | Method for the preparation of aminophosphine ligands and their use in metal catalysts |
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CA002591126A CA2591126A1 (en) | 2007-06-08 | 2007-06-08 | Process for the preparation of aminiphosphine ligands and their use in metal catalysts |
CA2591126 | 2007-06-08 |
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CN112824421A (en) * | 2019-11-21 | 2021-05-21 | 中国科学院大连化学物理研究所 | Chiral phosphine-phosphoramidite ligand and preparation method and application thereof |
CN114539319A (en) * | 2020-11-24 | 2022-05-27 | 中国科学院大连化学物理研究所 | Novel chiral phosphine-dicyclic phosphoramidite ligand and preparation method and application thereof |
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EP2215101A4 (en) * | 2007-10-30 | 2013-04-24 | Kanata Chemical Technologies Inc | Cationic transition metal catalysts |
CN114106057B (en) | 2016-10-19 | 2023-06-23 | 优美科股份公司及两合公司 | Synthesis and characterization of Ru alkylene complexes |
WO2019193483A1 (en) | 2018-04-06 | 2019-10-10 | Kamal Pharmachem Inc. | Catalytic conversion of carbon dioxide to methanol |
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US6590115B2 (en) * | 2000-09-29 | 2003-07-08 | Eastman Chemical Company | Phosphino-aminophosphines |
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ES2305095T3 (en) | 2000-09-13 | 2008-11-01 | Firmenich S.A. | CATALYTIC HYDROGENATION PROCESSES. |
WO2004096735A2 (en) * | 2003-05-02 | 2004-11-11 | Kamaluddin Abdur-Rashid | Transfer hydrogenation processes and catalysts |
CN1768944A (en) * | 2004-11-01 | 2006-05-10 | 中国科学院大连化学物理研究所 | Catalyst using phosphine-phosphoramidite ester as ligand, its preparation method and application |
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US115A (en) | 1837-01-31 | Machine fob boring and mortising | ||
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN112824421A (en) * | 2019-11-21 | 2021-05-21 | 中国科学院大连化学物理研究所 | Chiral phosphine-phosphoramidite ligand and preparation method and application thereof |
CN114539319A (en) * | 2020-11-24 | 2022-05-27 | 中国科学院大连化学物理研究所 | Novel chiral phosphine-dicyclic phosphoramidite ligand and preparation method and application thereof |
CN114539319B (en) * | 2020-11-24 | 2024-04-12 | 中国科学院大连化学物理研究所 | Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof |
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AU2008258233A1 (en) | 2008-12-11 |
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JP5466152B2 (en) | 2014-04-09 |
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AU2008258233C1 (en) | 2014-08-07 |
WO2008148202A4 (en) | 2009-02-19 |
EP2167515A4 (en) | 2012-04-18 |
US8658825B2 (en) | 2014-02-25 |
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