CN101565435A - P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 - Google Patents
P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 Download PDFInfo
- Publication number
- CN101565435A CN101565435A CNA2009101377911A CN200910137791A CN101565435A CN 101565435 A CN101565435 A CN 101565435A CN A2009101377911 A CNA2009101377911 A CN A2009101377911A CN 200910137791 A CN200910137791 A CN 200910137791A CN 101565435 A CN101565435 A CN 101565435A
- Authority
- CN
- China
- Prior art keywords
- phospholanes
- nmr
- alkyl
- cdcl
- asymmetric
- 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
- 150000004850 phospholanes Chemical class 0.000 title claims description 21
- 238000006555 catalytic reaction Methods 0.000 title abstract description 26
- 150000003843 phosphocyclic compounds Chemical class 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 47
- 239000003446 ligand Substances 0.000 claims abstract description 30
- 150000002500 ions Chemical class 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 239000011541 reaction mixture Substances 0.000 claims description 18
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 12
- 230000005595 deprotonation Effects 0.000 claims description 9
- 238000010537 deprotonation reaction Methods 0.000 claims description 9
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 7
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 20
- 238000002360 preparation method Methods 0.000 abstract description 20
- 239000003054 catalyst Substances 0.000 abstract description 8
- 238000006317 isomerization reaction Methods 0.000 abstract description 8
- 238000005698 Diels-Alder reaction Methods 0.000 abstract description 4
- 238000007341 Heck reaction Methods 0.000 abstract description 4
- 238000006845 Michael addition reaction Methods 0.000 abstract description 4
- 238000006579 Tsuji-Trost allylation reaction Methods 0.000 abstract description 4
- 238000005865 alkene metathesis reaction Methods 0.000 abstract description 4
- 238000006352 cycloaddition reaction Methods 0.000 abstract description 4
- 238000006735 epoxidation reaction Methods 0.000 abstract description 4
- 238000007871 hydride transfer reaction Methods 0.000 abstract description 4
- 238000006197 hydroboration reaction Methods 0.000 abstract description 4
- 238000007037 hydroformylation reaction Methods 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- 238000005575 aldol reaction Methods 0.000 abstract 1
- 238000005888 cyclopropanation reaction Methods 0.000 abstract 1
- 238000006267 hydrovinylation reaction Methods 0.000 abstract 1
- 239000013256 coordination polymer Substances 0.000 description 108
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 30
- 239000000203 mixture Substances 0.000 description 27
- SJNUZTRUIDRSJK-KNCCTNLNSA-N (1s,2r)-1-tert-butyl-2-[(1s,2r)-1-tert-butylphospholan-2-yl]phospholane Chemical compound CC(C)(C)[P@]1CCC[C@@H]1[C@@H]1[P@@](C(C)(C)C)CCC1 SJNUZTRUIDRSJK-KNCCTNLNSA-N 0.000 description 25
- 125000003118 aryl group Chemical group 0.000 description 25
- -1 ferrocenyl Chemical class 0.000 description 25
- 238000004679 31P NMR spectroscopy Methods 0.000 description 22
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 22
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 18
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 16
- 125000000547 substituted alkyl group Chemical group 0.000 description 16
- 125000003107 substituted aryl group Chemical group 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 14
- 125000001072 heteroaryl group Chemical group 0.000 description 14
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- 238000005984 hydrogenation reaction Methods 0.000 description 12
- 239000011159 matrix material Substances 0.000 description 12
- 229910052723 transition metal Inorganic materials 0.000 description 12
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000007872 degassing Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 229910018286 SbF 6 Inorganic materials 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 125000004104 aryloxy group Chemical group 0.000 description 7
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 241000761456 Nops Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 238000011914 asymmetric synthesis Methods 0.000 description 6
- QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical group COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 5
- NHNUFAASKXPOQA-UHFFFAOYSA-N (3-acetamido-2-hydroxyphenyl)arsonic acid Chemical compound C(C)(=O)NC=1C(=C(C=CC1)[As](O)(=O)O)O NHNUFAASKXPOQA-UHFFFAOYSA-N 0.000 description 5
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- OKQKDCXVLPGWPO-UHFFFAOYSA-N sulfanylidenephosphane Chemical compound S=P OKQKDCXVLPGWPO-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- 230000007306 turnover Effects 0.000 description 4
- UFSZDRZMKJSOOM-UHFFFAOYSA-N 1-tert-butylphospholane Chemical class CC(C)(C)P1CCCC1 UFSZDRZMKJSOOM-UHFFFAOYSA-N 0.000 description 3
- BWJRMVLPCQPWGR-UHFFFAOYSA-N boron;phosphane Chemical compound [B].P BWJRMVLPCQPWGR-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000006459 hydrosilylation reaction Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 2
- PEBXLTUWFWEWGV-UHFFFAOYSA-N 1-methyl-2-(2-phenylethenyl)benzene Chemical compound CC1=CC=CC=C1C=CC1=CC=CC=C1 PEBXLTUWFWEWGV-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000002877 alkyl aryl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 150000001576 beta-amino acids Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 239000012018 catalyst precursor Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003003 phosphines Chemical class 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- WVQBLGZPHOPPFO-LBPRGKRZSA-N (S)-metolachlor Chemical compound CCC1=CC=CC(C)=C1N([C@@H](C)COC)C(=O)CCl WVQBLGZPHOPPFO-LBPRGKRZSA-N 0.000 description 1
- VNNDVNZCGCCIPA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;manganese Chemical compound [Mn].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O VNNDVNZCGCCIPA-FDGPNNRMSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 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
- IKSGBQXPXOUDJB-UHFFFAOYSA-N COC(CCC1=CC=CC=C1)=O.C(C)(=O)NC1=C(C=CC=C1O)[As](O)(O)=O Chemical class COC(CCC1=CC=CC=C1)=O.C(C)(=O)NC1=C(C=CC=C1O)[As](O)(O)=O IKSGBQXPXOUDJB-UHFFFAOYSA-N 0.000 description 1
- 229910020366 ClO 4 Inorganic materials 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910021115 PF 6 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 150000004646 arylidenes Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- AASUFOVSZUIILF-UHFFFAOYSA-N diphenylmethanone;sodium Chemical compound [Na].C=1C=CC=CC=1C(=O)C1=CC=CC=C1 AASUFOVSZUIILF-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000005373 pervaporation Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- GWLJTAJEHRYMCA-UHFFFAOYSA-N phospholane Chemical compound C1CCPC1 GWLJTAJEHRYMCA-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003643 water by type Substances 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
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B31/00—Reduction in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/16—Preparation of optical isomers
- C07C231/18—Preparation of optical isomers by stereospecific synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/20—Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
- C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
- C07C45/505—Asymmetric hydroformylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
- C07C5/32—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by dehydrogenation with formation of free hydrogen
- C07C5/327—Formation of non-aromatic carbon-to-carbon double bonds only
- C07C5/333—Catalytic processes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/283—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F11/00—Compounds containing elements of Groups 6 or 16 of the Periodic Table
- C07F11/005—Compounds containing elements of Groups 6 or 16 of the Periodic Table compounds without a metal-carbon linkage
-
- 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
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
- C07F15/004—Iridium compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/006—Palladium compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/006—Palladium compounds
- C07F15/0066—Palladium compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium compounds
- C07F15/008—Rhodium compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
- C07F15/045—Nickel compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/003—Compounds containing elements of Groups 4 or 14 of the Periodic Table without C-Metal linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/005—Compounds of elements of Group 5 of the Periodic Table without metal-carbon linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- 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
-
- 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
-
- 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
- C07F9/65685—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 oxide or thioxide
-
- 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
-
- 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
-
- 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
- C07F9/6581—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 nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—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 nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- C07C2531/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- C07C2531/24—Phosphines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Furan Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Abstract
本发明公开了用于不对称催化的手性配体和基于此类手性配体的金属配合物。根据本发明的金属配合物可在不对称反应,例如氢化、氢负离子转移、加氢羧基化、氢化硅烷化、硼氢化、加氢乙烯基化、加氢甲酰基化、烯丙位烷基化、烯烃易位、异构化、环丙烷化、狄尔斯-阿德耳反应、Heck反应、醛醇缩合反应、迈克尔加成、环氧化、动力学拆分和[m+n]环加成反应中用作催化剂。另外描述了所述配体的制备方法。
Description
本申请是2002年11月8日提交的、发明名称为“P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途”的中国发明专利申请02826029.5的分案申请。
发明背景
1.本发明的领域
本发明涉及衍生自P-手性磷杂戊环(phospholane)和P-手性磷环化合物的新型手性配体以及用于不对称催化中的催化剂。更具体地说,本发明涉及这些手性膦配体的过渡金属配合物,其可以用作不对称反应中的催化剂,所述不对称反应例如是氢化、氢负离子转移、加氢羧基化、氢化硅烷化、硼氢化、加氢乙烯基化、加氢甲酰基化、烯丙位烷基化、烯烃易位、异构化、环丙烷化、狄尔斯-阿德耳反应、Heck反应、醛醇缩合反应、迈克尔加成、环氧化作用、动力学拆分和[m+n]环化加成。
2.现有技术的叙述
分子手性在科学技术中具有重要作用。许多药物、香料、食品添加剂和农用化学品的生物活性常常与它们的绝对分子构型有关。在药物和精细化学品工业中日益增长的需求是开发出用于制备单一对映异构体产品的成本有效的工艺。为了满足这种需求,化学家已经探索出许多获得对映异构体纯净的化合物的方法,所述方法涉及从天然手性物质的旋光拆分和结构变换到采用合成手性催化剂和酶的不对称催化作用。在这些方法中,不对称催化可能是最有效的,因为可以使用少量手性催化剂生产大量的手性目标分子[Book,Ojima,I.编辑的Catalytic Asymmetric Synthesis(《催化不对称合成》),VCH,New York,1993和Noyori,R.Asymmetric Catalysis In OrganicSynthesis(《有机合成中的不对称催化》),John Wiley&Sons Inc.,New York,1994]。
不对称氢化占据所有工业规模的不对称合成的主要部分。不对称合成的一些令人注目的工业应用实例包括Monsanto的L-DOPA合成(脱氢氨基酸的不对称氢化,94%ee,使用Rh-DIPAMP配合物的20,000周转率)[Knowles,W.S.Acc.Chem.Res.1983,16,106],Takasago的L-薄荷醇的合成(不对称异构化,98%ee,使用Rh-BINAP配合物的300,000周转率)[Noyori,R.;Takaya,H.Acc.Chem.Res.1990,23,345]和Norvatis的(S)-异丙甲草胺合成(亚胺的不对称氢化,80%ee,利用Ir-二茂铁基膦配合物的1,000,000周转率)[Spindler,F.;Pugin,B.;Jalett,H.-P.,Buser,H.-P.;Pittelkow,U.;Blaser,H.-U.,Altanta,1996;Chem.Ind.(Dekker),1996,63和Tongni,A.Angew.Chem.Int.Ed.Engl.1996,356,14575]。
用于过渡金属催化反应中的手性配体的发明在不对称催化中具有关键作用。不仅对映选择性取决于手性配体的结构,而且常常可以通过改变配体的立体和电子结构来改变反应性。
近年来,大量手性配体已被开发用于不对称催化反应中。尽管如此,发现只有少数手性配体适合用于工业中以生产要求高选择性的手性分子。
最早的P-手性膦配体之一是DIPAMP,它由Knowles,J.Am.Chem.Soc.(《美国化学协会杂志》),99,5946(1977)研制。该Rh(I)-DIPAMP配合物已经被用于L-DOPA的合成中。
许多研究小组不断努力发展制备不对称催化用的P-手性配体的策略,其包括例如以下这些:I.Ojima编辑的Catalytic Asymmetric Synthesis,第二版,出版者VCH,Wheinheim,2000;Juge和Genet,Tetrahedron Lett.(《四面体快报》),30,6357(1989),他们开发了制备P-手性膦的方法;E.J.Corey,J.Am.Chem.Soc.,115,11000(1993),他已经开发出用于制备P-手性膦和二膦的方法。作为合成P-手性膦用的方法的对映选择性去质子化已经由Evans,J.Am.Chem.Soc.,117,9075(1995)应用。典型地,膦-硼烷、硫化膦已被使用。这些化合物的对映选择性去质子化和Cu-调节的偶联反应可以制备若干二膦。Cu-调节的偶联反应已由Mislow,J.Am.Chem.Soc.,95,5839(1973)作了报道。膦-硼烷的形成和硼烷的除去已由Imamoto,J.Am.Chem.Soc.,112,5244(1990),Yamago,J.Chem.Soc.(《化学协会杂志》),Chem.Commun.,2093(1994)和Livinghouse,Tetrahedron Lett.,35,9319(1994)作了报道。硫化膦的脱硫作用已由Mislow,J.Am.Chem.Soc.,91,7023(1969)作了报道。最近,Imamoto已经成功地使用了这些方法来制备多种P-手性膦,例如BisP*,J.Am.Chem.Soc.,123,5268(2001),MiniPhos,J.Org.Chem.(《有机化学杂志》),64,2988(1999)和其它混合的P-手性配体,Org.Lett.(《有机快报》),3,373(2001)。
这些配体已经有效地用于许多不对称反应中,特别是用于不对称氢化反应中,例如Adv.Synth.Catal.(《高级合成催化剂》),343,118(2001)中描述的那些。
以下描述了这些配体中的一部分:
尽管上述配体中的取代基变化范围宽,但是这些配体中的大部分是DIPAMP配体的衍生物。这些配体的可能缺点在于具有DIPAMP结构的配体在构象上是灵活的,并且因此难以使对映选择性最优化。
与现有技术的配体相比,本发明提供了磷杂戊环和磷环结构以限制构象灵活性,从而可以在由这些配体制备的过渡金属催化剂中实现高对映选择性。
因此,从立体化学的角度而言,通常生成附加的立构产生中心(seterogenic center)(例如四个或更多个立构产生中心)以使得本发明的新型配体在不对称催化反应中比例如具有仅仅两个立构产生中心的DIPAMP和BisP*配体的选择性明显更好。
发明概述
本发明提供由下式表示的手性配体或其对映异构体:
其中X是选自(CR4R5)n、(CR4R5)n-Z-(CR4R5)n和由下式表示的基团中的二价基团:
其中各n独立地是1-6的整数;其中各R4和R5可以独立地是氢、烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁基、卤素、羟基、烷氧基、芳氧基、烷硫基、芳硫基和酰胺基;和
其中Z可以是O、S、-COO-、-CO-、O-(CR4R5)n-O、CH2(C6H4)、CH2(Ar)、CH2(杂芳基)、链烯基、CH2(链烯基)、C5H3N、二价芳基、2,2’-二价-1,1’-联苯基、SiR’2、PR’和NR6,其中R’和R6中的每一个可以独立地是氢、烷基、取代烷基、芳基、取代芳基、羟基、烷氧基、芳氧基、酰基和烷氧基羰基;
其中R可以是烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁基、烷氧基和芳氧基;
其中E可以是PR’2、PR’R”、邻位取代的吡啶基、噁唑啉、手性噁唑啉、CH2(手性噁唑啉)、CR’2(手性噁唑啉)、CH2PR’2、CH2(邻位取代的吡啶基)、SiR’3、CR’2OH和由下式表示的基团:
其中Y可以是
(CR4R5)m和(CR4R5)m-Z-(CR4R5)m,
其中各m独立地是0-3的整数;其中各R4和R5可以独立地是氢、烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁基、卤素、羟基、烷氧基、芳氧基、烷硫基、芳硫基和酰胺基;和其中Z可以是O、S、-CO-、-COO-、O-(CR4R5)n-O、CH2(C6H4)、CH2(Ar)、CH2(杂芳基)、链烯基、CH2(链烯基)、C5H3N、二价芳基、2,2’-二价-1,1’-联苯基、SiR’2、PR’和NR6,其中R’和R6中的每一个可以独立地是氢、烷基、取代烷基、芳基、取代的芳基、羟基、烷氧基、芳氧基、酰基和烷氧基羰基。
更具体地说,本发明提供由下式表示的手性配体和其对映异构体:
其中R可以是烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁基、烷氧基和芳氧基;和
其中n是0-2。
本发明进一步提供了由以下方法制备的催化剂,该方法包括:
将过渡金属盐或其配合物与如以上所述的根据本发明的手性配体接触。
本发明还进一步提供了制备不对称化合物的方法,其包括:
将能够由不对称反应形成不对称产物的基体与催化剂接触,所述催化剂由包括将过渡金属盐或其配合物与如以上所述的根据本发明的手性配体接触的方法制备。
本发明还进一步提供了制备(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的方法,该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生1-烷基-磷杂戊环-1-硫化物的阴离子;和
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物。
更进一步地,本发明提供了制备(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环的方法,该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生1-烷基-磷杂戊环-1-硫化物的阴离子;
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物;
从反应混合物中重结晶该(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物;和
将(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物和六氯乙硅烷在溶剂中接触,以产生(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环。
本发明的新型配体中存在的附加立构产生中心(例如四个或更多个立构产生中心)使得它们在不对称催化反应中比例如具有仅仅两个立构产生中心的DIPAMP和BisP*配体的选择性明显更好。
发明详述
本发明提供了新型的P-手性磷杂戊环和磷环化合物并描述了它们在不对称催化中的用途。
环状结构的引入可以限制与膦相邻的取代基的旋转以及对膦周围的这些基团的取向控制可以导致不对称反应的有效的手性诱导。这些膦的金属配合物和相关的非C2对称配体的金属配合物可用于许多不对称反应。
配体手性环境的可调性对于实现高对映选择性是关键的。可以通过环尺寸和取代基的变化来精确调节构象刚性的环状膦类的立体结构和电子结构。
已经开发了几种新型的手性膦用于不对称催化反应。用这些手性配体体系已开发了多种不对称反应,例如氢化、氢负离子转移、烯丙位烷基化、氢化硅烷化、硼氢化、加氢乙烯基化、加氢甲酰基化、烯烃易位、加氢羧基化、异构化、环丙烷化、狄尔斯-阿德耳反应、Heck反应、异构化、醛醇缩合反应、迈克尔加成、环氧化、动力学拆分和[m+n]环化加成。
本发明的配体可以是对映异构体的外消旋混合物。优选地,配体是对映异构体的非外消旋混合物,并且更优选地,配体是对映异构体中的一种。
优选地,配体具有至少85%ee的光学纯度,并且更优选地,配体具有至少95%ee的光学纯度。
下面给出了本发明的手性配体的代表性实例。可以制备根据本发明的许多具有所需结构的手性配体并用于本发明中所述的催化剂的制备中。
X=(CH2)n,n=1、2、3、4、5、6。CH2OCH2、CH2NHCH2、CH2CH(R’)CH(R’)、CH2CH(OR’)CH(OR’)、CH2CH(OH)CH(OH)、CH2CH(OCR’2O)CH、CH2CH(O烷基O)CH、CH2CH(OCHR’O)CH、CH2NR’CH2、CH2CH2NR’CH2、CH2CH2O-CH2、CH2(C6H4)、CH2(Ar)、CH2(杂芳基)、CH2(链烯基)、烷基、取代烷基、芳基、取代芳基、CH2(联芳基)、CH2(二茂铁),
R=烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁
E=PR’2、PR’R”、o-取代吡啶、噁唑啉、手性噁唑啉、CH2(手性噁唑啉)、CR’2(手性噁唑啉)、CH2PR’2、CH2(o-取代吡啶)、SiR’3、CR’2OH
Y=(CH2)n,n=0、1、2、3,CH2NHCH2,、CR’2、CO、SiR’2、C5H3N、C6H4、烷基、取代烷基、二价芳基、2,2’-二价-1,1’-联苯基、取代芳基、杂芳基、二茂铁
R’=烷基、芳基、取代烷基、取代芳基、烷基芳基、H。
在这些配体中,磷环化合物的桥基X是(CH2)n,n=1、2、3、4、5、6;CH2OCH2、CH2NHCH2、CH2CH(R’)CH(R’)、CH2CH(OR’)CH(OR’)、CH2CH(OH)CH(OH)、CH2CH(OCR’2O)CH、CH2CH(O烷基O)CH、CH2CH(OCHR’O)CH、CH2NR’CH2、CH2CH2NR’CH2、CH2CH2OCH2、CH2(C6H4)、CH2(Ar)、CH2(杂芳基)、CH2(链烯基)、烷基、取代烷基、芳基、取代芳基、CH2(联芳基)、CH2(二茂铁)。R是烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁。其中E是PR’2、PR’R’′、o-取代吡啶、噁唑啉、手性噁唑啉、CH2(手性噁唑啉)、CR’2(手性噁唑啉)、CH2PR’2、CH2(o-取代吡啶)、SiR’3、CR’2OH。
Y可以是(CH2)n,n=0、1、2、3,CH2NHCH2、CH2SCH2、CH2PR’CH2、CR’2、CO、SiR’2、C5H3N、C6H4、烷基、取代烷基、二价芳基、2,2’-二价-1,1’-联苯基、取代芳基、杂芳基、二茂铁。R’=烷基、芳基、取代烷基、取代芳基、烷基芳基、H。
在优选的实施方案中,本发明的配体包括由这些通式表示的化合物,其中:
X可以是(CH2)n,其中n是1-6,CH2OCH2、CH2NHCH2、CH2CH(R’)CH(R’)、CH2CH(OR’)CH(OR’)、CH2NR’CH2、CH2CH(OH)CH(OH)、CH2CH2NR’CH2、CH2CH2OCH2和由下式表示的基团:
其中各R4和R5可以独立地是氢、烷基、芳基、取代烷基和取代芳基;和其中:
Y可以是(CH2)n,其中n是0-3,CH2NHCH2、CH2SCH2、CH2PR’CH2、CR’2、CO、SiR’2、C5H3N、C6H4、亚烷基、取代亚烷基、1,2-二价亚芳基、2,2’-二价-1,1’-联苯基、取代芳基、杂芳基和二茂铁。
更具体地说,手性配体可以由下式和其对映异构体表示:
其中R可以是烷基、芳基、取代烷基、取代芳基、杂芳基、二茂铁基、烷氧基和芳氧基;和
其中n是0-2;
R可以是CH3、Et、iPr、t-Bu、1-金刚烷基、Et3C、环C5H9、环C6H11、苯基、对甲苯基、3,5-二甲基苯基、3,5-二叔丁基苯基、邻甲氧苯基和萘基。
此类配体的实例包括由下式表示的配体和其对映异构体:
和由下式表示的配体和其对映异构体:
根据本发明的配体可以是膦硼烷、硫化膦或氧化膦的形式。
下面列出特定手性配体的供选择的实例以便说明新型的P-手性磷杂戊环和P-手性磷环化合物(L1-L35)。
对于各配体,相应的对映异构体也考虑到了。这些化合物可以从相应的膦-硼烷、硫化膦和氧化膦制备。
因为Ir-催化的不对称氢化仍然是高度依赖基体的,所以开发用于Ir-催化氢化的新型高效的手性配体继续面临挑战。在开发了用于Ir-催化不对称氢化的膦基噁唑啉后,Pfaltz以及其他人员继续努力寻找新型高效的P,N配体(A.Lightfoot,P.Schnider,A.Pfaltz,Angew.Chem.Int.Ed.1998,37,2897-2899)。随后由Pfaltz和同事开发了多种P,N配体如TADDOL-亚磷酸酯-噁唑啉,PyrPHOX和次膦酸酯-噁唑啉(J.Blankenstein,A.Pfaltz,Angew.Chem.Int.Ed.2001,40,4445-4447)。Burgess还报导了JM-Phos和咪唑叉基-噁唑啉(D.-R.Hou,J.H.Reibenspies,K.Burgess,J.Org.Chem.2001,66,206-215;M.T.Powell,D.-R.Hou,M.C.Perry,X.Cui,K.Burgess,J.Am.Chem.Soc.2001,123,8878-8879)。
在本发明中,我们还报道了用干Ir-催化不对称氢化的一类新的手性P,N配体、磷杂戊环-噁唑啉。已经在甲基均二苯代乙烯和甲基肉桂酸酯的氢化中获得优异的对映异构选择性。
本发明还提供了由包括以下步骤的方法制备的催化剂:
将过渡金属盐或其配合物和如以上所述的根据本发明的手性配体接触。
用于制备催化剂的合适过渡金属包括Ag、Pt、Pd、Rh、Ru、Ir、Cu、Ni、Mo、Ti、V、Re和Mn。
如上所述,该催化剂可以通过将过渡金属盐或其配合物和根据本发明的配体接触来制备。
合适的过渡金属盐或配合物包括下列物质:
AgX;Ag(OTg);Ag(OTf)2;AgOAc;PtCl2;H2PtCl4;Pd2(DBA)3;Pd(OAc)2;PdCl2(RCN)2;(Pd(烯丙基)Cl)2;Pd(PR3)4;(Rh(NBD)2)X;(Rh(NBD)Cl)2;(Rh(COD)Cl)2;(Rh(COD)2)X;Rh(acac)(CO)2;Rh(乙烯)2(acac);(Rh(乙烯)2Cl)2;RhCl(PPh3)3;Rh(CO)2Cl2;RuHX(L)2(二膦),RuX2(L)2(二膦),Ru(芳烃)X2(二膦),Ru(芳基)X2;Ru(RCOO)2(二膦);Ru(甲代烯丙基)2(二膦);Ru(芳基)X2(PPh3)3;Ru(COD)(COT);Ru(COD)(COT)X;RuX2(甲基·异丙基苯);Ru(COD)n;Ru(芳基)X2(二膦);RuCl2(COD);(Ru(COD)2)X;RuX2(二膦);RuCl2(=CHR)(PR’3)2;Ru(ArH)Cl2;Ru(COD)(甲代烯丙基)2;(Ir(NBD)2Cl)2;(Ir(NBD)2)X;(Ir(COD)2Cl)2;(Ir(COD)2)X;CuX(NCCH3)4;Cu(OTf);Cu(OTf)2;Cu(Ar)X;CuX;Ni(acac)2;NiX2;(Ni(烯丙基)X)2;Ni(COD)2;MoO2(acac)2;Ti(OiPr)4;VO(acac)2;MeReO3;MnX2和Mn(acac)2。
在这些中各R和R’独立地选自烷基或芳基;Ar是芳基;和X是抗衡阴离子。
在以上过渡金属盐和配合物中,L是溶剂和抗衡阴离子X可以是卤素、BF4、B(Ar)4,其中Ar是氟苯基或3,5-二-三氟甲基-1-苯基、ClO4、SbF6、PF6、CF3SO3、RCOO或它们的混合物。
在另一个方面,本发明包括使用如上所述的催化剂制备不对称化合物的方法。该方法包括将能够由不对称反应形成不对称产物的基体和根据本发明的催化剂接触的步骤,其中所述催化剂通过过渡金属盐或其配合物和本发明的配体接触而制备。
合适的不对称反应包括不对称氢化、氢负离子转移、烯丙位烷基化、氢化硅烷化、硼氢化、加氢乙烯基化、加氢甲酰基化、烯烃易位、加氢羧基化、异构化、环丙烷化、狄尔斯-阿德耳反应、Heck反应、异构化、醛醇缩合反应、迈克尔加成、环氧化、动力学拆分和[m+n]环化加成,其中m=3-6和n=2。
优选地,所述不对称反应是氢化并且待氢化的基体是烯属不饱和化合物、亚胺、酮、烯胺、烯酰胺和乙烯基酯。
本发明还进一步包括制备不对称化合物的方法,该方法包括:
将能够由不对称反应形成不对称产物的基体和催化剂接触,其中所述催化剂由包括将过渡金属盐或其配合物和如以上所述的根据本发明的手性配体接触的方法制备。
本发明还进一步包括制备(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的方法,该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生1-烷基-磷杂戊环-1-硫化物的阴离子;和
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物。
更进一步地,本发明包括制备(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环的方法。
该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生1-烷基-磷杂戊环-1-硫化物的阴离子;
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物;
从反应混合物中重结晶该(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物;和
将(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物和六氯乙硅烷在溶剂中接触以产生(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环。
优选地,(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环是从含有叔丁基团的合适原料制备的(1S,1S’,2R,2R’)-1,1’-二叔丁基-[2,2’]-联磷杂戊环。
下面描述了制备根据本发明的手性配体的几种合适的方法。
(a)采用不对称去质子化的TangPhos的合成
(b)经由手性分离的TangPhos的合成
(c)利用骨架手性的TangPhos配体的合成
(d)利用手性汇合(pool)方法的TangPhos配体的合成
(e)用于不对称催化的PN配体的合成
(a)nBuLi,金雀花碱,CO2;(b)氨基醇,EDC,HOBT,DMF,然后MsCl;(c)阮内镍
一般程序
所有的反应和控制是在充氮的手套箱中或通过使用标准Schlenk技术进行。THF和甲苯是在氮气氛围中干燥并从二苯甲酮羰游基钠中蒸馏出来。从CaH2蒸馏出二氯甲烷。在氮气氛围中从Mg蒸馏出甲醇。在使用之前在甲苯中将(R,R)-BDNPB配制成10mg/ml的溶液。柱色谱法通过使用EM硅胶60(230~400目)进行。1H,13C和31P NMR是在Bruker WP-200,AM-300和AMX-360分光光度计上记录的。自四甲基硅烷的低磁场以ppm记录化学位移,其中溶剂共振作为内标。旋光度是在Perkin-Elmer 241旋光计上获得的。MS谱是在用于LR-EI和HR-EI的KRATOS质谱仪MS9/50上记录的。GC分析是通过使用手性毛细管柱在Helwett-Packard 6890气相色谱仪上进行的。HPLC分析是在WatersTM 600色谱分析仪上进行的。
实施例1:TangPhos(1)的合成
已经开发了有效的三步合成手性C2对称P-手性二磷杂戊环的方法。
1-叔丁基-磷杂戊环1-硫化物的制备
BrMgCH2(CH2)2CH2MgBr的制备。在室温下向装有在300ml干燥THF中的镁屑(7.92g,0.33mol)的干燥Schlenk烧瓶中逐滴加入在50mlTHF中的1,4-二溴丁烷(23.7g,0.11mol)。该反应在加料过程中强烈放热。在加料结束(1小时内)后,所得的暗色溶液在室温下再保持2小时。整个溶液直接用于后续反应。
在-78℃下向THF(300ml)中的三氯化磷(13.7g,0.10mol)溶液中逐滴加入t-BuMgCl的THF溶液(100mL,1.0M)。2小时内完成加料。混合物于-78℃下放置1小时后,逐滴加入THF中的BrMgCH2(CH)2CH2MgBr溶液(以上制得)。2小时内完成加料。混合物然后经2小时升温至室温并搅拌一夜。
在室温下,一次性向反应混合物中添加硫粉(4.8g,0.15mol)。所得溶液进一步在室温下搅拌2小时。然后添加水(300ml)。向THF层中添加500mL EtOAc。用水(300mL)洗涤该有机层,随后用盐水(300mL)洗涤,在Na2SO4上干燥,并浓缩。所得的油通过硅胶柱,随后重结晶而得到无色结晶产物1-叔丁基-磷杂戊环1-硫化物8g(45%产率)。
(1R,1R’,2R,2R’)-1,1’-二叔丁基-[2,2’]-联磷杂戊环-1,1’-二硫化物的合成
在-78℃下,向乙醚(200mL)中的(-)-金雀花碱(7.83mL,34mmol)溶液中逐滴加入正丁基锂(21.3mL,34mmol,1.6M己烷溶液)。所得的溶液在-78℃下保持30分钟。然后在这一温度下,向该溶液逐滴加入1-叔丁基-磷杂戊环1-硫化物(5.0g,28.4mmol,在乙醚(100mL)中)的溶液。1小时内完成加料。所得的混合物保持在-78℃下并再搅拌8小时。然后一次性将干燥的CuCl2(5.73g,42.6mmol)加到该溶液中。剧烈搅拌得到的悬浮液并经4小时升至室温。添加150ml浓氨水。该水层用EtOAc洗涤两次(2×100mL)。合并的有机相另外依次用5%氨水(100mL),1N HCl(100mL),水(100mL)和盐水(100mL)洗涤。在Na2SO4上干燥后,在减压下浓缩该溶液而得到油状固体,随后通过硅胶柱提纯而得到(1R,1R’,2R,2R’)-1,1’-二-叔丁基-[2,2’]-联磷杂戊环1,1’-二硫化物(72%ee,83%)和内消旋化合物(1R,1R’,2S,2S’)-1,1’-二叔丁基-[2,2’]-联磷杂戊环1,1’-二硫化物(17%)的固体混合物(4g)。
从乙酸乙酯和乙醇中重结晶该混合物而得到700mg纯产物(1R,1R’,2R,2R’)-1,1’-二-叔丁基-[2,2’]-联磷杂戊环1,1’-二硫化物(根据HPLCee:>99%,总产率:14%)。
(1S,1S’,2R,2R’)-1,1’-二-叔丁基-[2,2’]-联磷杂戊环TangPhos(1)的合成
向25ml苯中的(1R,1R’,2R,2R’)-1,1’-二叔丁基-[2,2’]-联磷杂戊环1,1’-二硫化物(440mg,1.26mmol)溶液中添加六氯乙硅烷(3.25mL,5.08g,18.9mmol)。混合物在回流下搅拌4小时。当溶液冷却到室温后,将50mL的脱气30%(w/w)NaOH溶液小心地加入到有冰-水浴的反应混合物中。然后在60℃下搅拌所得的混合物,直到水层变得透明。分离两相。用脱气苯洗涤水相两次(2×30mL)。混合的苯在Na2SO4上干燥和浓缩。
固体残留物重新溶于最少量的脱气二氯甲烷中,其随后通过碱性Al2O3管塞(洗脱液:Et2O∶己烷=1∶10)而得到纯白色产物(1)320mg(88%产率)。
实施例2:脱氢氨基酸的不对称氢化
不对称氢化的一般程序
向手套箱内的THF(10mL)中的[Rh(COD)2]BF4(5.0mg,0.012mmol)溶液中添加手性膦配体(0.15mL TangPhos的0.1M甲苯溶液,0.015mmol)。搅拌混合物30分钟后,添加脱氢氨基酸(1.2mmol)。所述氢化于室温下在20psi氢气中进行24小时。反应混合物用CH2N2处理,然后真空浓缩。该残留物通过短硅胶柱以除去催化剂。使用Chirasil-VAL III FSOT柱通过GC测量对映异构体过量。
通过将观察到的旋光度与报道值对比来确定产物的绝对构型。所有反应达到定量产率,并且GC没有发现副产物。
使用TangPhos(1)作为配体制备α氨基酸衍生物的不对称氢化示于下表中:
脱氢氨基酸衍生物的不对称氢化a
a该反应在室温和20psi H2压力下进行24小时。通过搅拌[Rh(NBD)2]SbF6和TangPhos在甲醇(2ml)中的溶液来原位制备催化剂[基体∶[Rh]∶TangPhos=1∶0.01∶0.011]。该反应达到100%的转化。b通过将旋光度与报道的数据对比来确认R绝对构型。c使用Chrialsil-VAL III FSOT柱通过手性GC测量对映异构体过量。d按相应甲酯测定。e使用Daicel ChiralcelOJ柱通过HPLC测定%ee。
实施例3:β-氨基酸衍生物的不对称合成
原料3-乙酰氨基-3-芳基-2-丙烯酸酯和3-乙酰氨基-3-杂芳基-2-丙烯酸酯的合成
典型的程序:原料3-乙酰氨基-3-苯基-2-丙烯酸甲酯可以根据已知的文献方法由三个步骤以良好的产率从便宜的乙酰苯方便地合成。所述文献是Zhu,G.;Zhen,Z.;Zhang,X.J.Org.Chem.1999,64,6907-6910;Krapcho,A.P.;Diamanti,J.Org.Synth.(《有机合成杂志》)1973,5,198-201。
1H-NMR(CDCl3,360MHz)δ(Z异构体)2.17(s,3H),3.77(s,3H),5.29(s,1H),7.37-7.45(m,5H);(E异构体)2.38(s,3H),3.77(s,3H),6.65(s,1H),7.37-7.45(m,5H)。
用Rh-TangPhos(1)体系制备β氨基酸衍生物的氢化
a该反应在20psi H2和室温下在THF中进行24小时。基体/[Rh(TangPhos)nbd]SbF6=200∶1。通过将旋光度与报道值对比来确定绝对构型。b使用Chiralselect 1000柱通过手性GC测定该ee(%)值。c对于E/Z混合物的E/Z比率。d使用(s,s)-whelk-01柱通过手性HPLC测定该ee。
对于β-芳基β-乙酰胺基丙烯酸酯的一般合成方法,参见Zhou,Y.-G.;Tang,W.;Wang,W.-B.;Li,W.;Zhang,X.J.Am.Chem.Soc.2002,124,4952-4953。对于β-烷基β-乙酰胺基丙烯酸酯的一般合成方法,参见Zhu,G.;Chen,Z.;Zhang,X.J.Org.Chem.1999,64,6907-6910。对于已知的基体和产物的分析数据,同样请参阅上述两篇文章。
3-乙酰氨基-3-(4-苄氧基苯基)-2-丙烯酸甲酯:
Z/E=9∶1;1H NMR(360MHz,CDCl3)δ(Z异构体)2.06(s,3H),3.65(s,3H),4.98(s,2H),5.18(s,1H),6.86(d,J=6.8Hz,2H),7.28(m,7H),10.46(s,1H);(E异构体)2.27(s,3H),3.65(s,3H),4.98(s,2H),6.44(s,1H),6.86(d,J=6.8Hz,2H),7.28(m,7H)。
β-烷基或β-芳基β-乙酰胺基丙烯酸酯的不对称氢化的一般程序
在充满氮气的手套箱中,向4mL脱气THF中的β-乙酰胺基丙烯酸酯(0.5mmol)溶液中添加Rh[(TangPhos)nbd]SbF6(2.5μmol)。将整个溶液转移到高压釜中。
该高压釜然后用氢气清洗三次,然后充填20psi压力的氢气。该反应器在室温下搅拌24小时。在释放氢气后,打开该高压釜并使反应混合物蒸发。
该残留物通过短硅胶栓塞而得到氢化产物β-氨基酸衍生物。少量的样品进行手性GC或HPLC分析。
3-乙酰氨基-3-(4-苄基氧基苯基)-丙酸甲基酯:
98.5%ee,[α]25D=-79.5°;1H NMR(300MHz,CDCl3)δ2.00(s,3H),2.83(dd,J=15.7,6.2Hz,1H),2.93(dd,J=15.6,6.0Hz,1H),3.63(s,3H),5.05(s,2H),5.40(m,1H),6.93(d,1H),6.94(dd,J=6.7,2.0Hz,2H),7.23(dd,J=6.8,1.8Hz,2H),6.72(m,5H);13C NMR(75MHz,CDCl3)δ23.8,40.2,49.5,52.2,115.4,127.9,128.0,128.4,129.0,133.3,137.3,158.6,169.7,172.1;MS(ESI)m/z 328(M++1);对于C19H22NO4的HRMS计算值328.1549,实测值328.1553。手性HPLC条件((s,s)-whelk-01):溶剂己烷∶异丙醇(1∶1);流速1mL/分钟;停留时间8.2分钟(R),13.1分钟(S)。
实施例4:烯酰胺的不对称氢化
表.使用TangPhos(1)的α-芳基烯酰胺的Rh-催化不对称氢化。
[a]条件:对于细节可参见实验部分。根据文献方法制备烯酰胺。[b]通过将旋光度与报道的数据对比来确定R绝对构型。使用Supelco Chiral Select1000柱通过手性GC或使用(R,R)-PolyWhelk-01柱通过手性HPLC来测定ee。
实施例5:使用Rh(TangPhos(1)催化剂的烯酰胺的不对称氢化的高周转率
[Rh(NBD)TangPhos(1)]+SbF6 -作为催化剂的不对称氢化:
α-脱氢氨基酸的氢化程序:
在手套箱中,向20mL脱气甲醇中的α-(乙酰氨基)-2-苯基丙烯酸甲酯(2.19g,10mmol)溶液中添加[Rh(nbd)(1)]SbF6(1mL 0.001M甲醇溶液,0.001mmol)。该氢化在室温和40psi氢气下进行8小时。在小心地释放氢气后,反应混合物通过短硅胶柱以除去催化剂。(R)-2-乙酰氨基-3-苯基丙酸甲酯的对映异构体过量通过手性GC直接测定(转化率:100%,ee:99.8%,TON:10,000)。
实施例6:利用Rh(TangPhos(1)催化剂的衣康酸衍生物的不对称氢化
项目 | R1 | R2 [b] | ee(%)[c] |
1 | H | H | 99 |
2 | CH3 | CH(CH3)2 | 96 |
3 | CH3 | Ph | 93 |
4 | CH3 | p-MeO-Ph | 97 |
5 | CH3 | p-Me-Ph | 97 |
6 | CH3 | p-Cl-Ph | >99 |
7 | CH3 | m-Cl-Ph | 99 |
8 | CH3 | 1-萘基 | 99 |
9 | CH3 | 2-萘基 | 99 |
[a]条件:催化剂前体=[Rh(TangPhos)(nbd)]SbF6(1mol%),室温,20psi H2,THF。通过与报道数据对比来确定产物的绝对构型。[b]大部分的基体(项目1除外)以2/1到>10/1的粗E/Z混合物使用。[c]在氢化产物转化成二甲酯后在手性GC或HPLC柱上测定。
实施例7:用[Rh(TangPhos(1))催化剂的芳基烯醇乙酸酯的不对称氢化
项目 | Ar | ee(%)[b] |
1 | 2-萘基 | 97 |
2 | Ph | 96 |
3 | p-F-Ph | 92 |
4 | p-Cl-Ph | 97 |
5 | 2-呋喃基 | 93 |
6 | p-NO2-Ph | 99 |
[a]条件:催化剂前体=[Rh(TangPhos)(nbd)]SbF6(1mol%),室温,20psi H2,EtOAc。通过与报道数据对比来确定产物的绝对构型。[b]在手性GC柱(chiral select 1000)上测定。
实施例8:用于不对称催化的手性PN配体的合成
因为Ir-催化的不对称氢化仍然是高度依赖基体的,所以用于Ir-催化氢化的新型高效的手性配体的开发继续面临挑战。一类新的手性P,N配体,磷杂戊环-噁唑啉已经按照以下方式制备出来:
在-78℃下,向乙醚(100mL)中的(-)-金雀花碱(14.4mL,62.5mmol)溶液中逐滴加入正丁基锂(1.6M己烷溶液,39mL,62.5mmol)。混合物在-78℃下搅拌30分钟。逐滴加入化合物2(10g,56.8mmol)在乙醚(150mL)中的溶液。1小时内完成加料。所得的反应混合物升至室温并搅拌一夜。混合物再冷却到-78℃。将CO2鼓泡通过该悬浮液2小时。然后通过添加1NHCl(200mL)及随后添加EtOAc(200mL)来猝灭该混合物。该有机层顺序地用1N HCl(200mL)、H2O(200mL)和盐水(100mL)洗涤。溶液在Na2SO4上干燥并蒸发。该残留物用2N NaOH溶液(300mL)处理。所得的透明溶液通过添加2N HCl来中和。经过真空过滤来收集该沉淀物而得到产物(8.0g,72%ee,64%产率)。该ee是通过用THF/CH3OH溶液中的TMSCHN2处理将产物转化成其相应的甲酯来测定的(对于甲酯的HPLC条件:Chiralpak AD柱;hex∶ipr=95∶5;8.8分钟,11.3分钟)。从乙醇中重结晶产物的样品(7.5g)两次,得到4.5g对映异构体纯净的产物3(>99.9%ee,40%总产率)。
3:[α]D 20=16.9°(c=0.9,CHCl3);1H NMR(360MHz,CDCl3)δ1.35(d,3JHP=17.0Hz,9H),1.71(m,1H),2.18(m,3H),2.47(m,2H),3.34(m,1H);13C NMR(90MHz,CD3OD)δ25.4(d,2JCP=1.7Hz),26.0(d,2JCP=2.2Hz),31.3(d,2JCP=7.3Hz),32.8(d,JCP=48.8Hz),36.1(d,JCP=44.1Hz),46.4(d,JCP=36.0),172.9;31P NMR(145MHz,CD3OD)δ89.3(s);APCI MS 121(M++H);对于C9H18PSO2的HRMS计算值221.0765,实测值221.0762。
3的甲酯:[α]D 20=42.6°(c=1,CHCl3);1H NMR(360MHz,CDCl3)δ1.21(d,3JHP=16.8Hz,9H),1.69(m,1H),1.92(m,2H),2.30(m,3H),3.23(m,1H),3.66(s,3H);13C NMR(90MHz,CDCl3)δ25.2(d,2.7Hz),25.4(d,2JCP=1.8Hz),29.9(d,2JCP=7.4Hz),31.7(d,JCP=47.9Hz),35.3(d,JCP=43.5Hz),45.4(d,JCP=35.5Hz),52.7,170.0;31P NMR(145MHz,CDCl3)δ87.8;APCI MS 235(M++H);对于C10H20PSO2的HRMS计算值235.0922,实测值235.0909。
化合物3(2.27mmol)、EDC.HCl(1.3g,6.82mmol)、HOBT.H2O(0.52g,3.41mmol)、手性氨基醇(3.41mmol)、三乙胺(1.9mL,13.6mmol)在10mLDMF中的混合物在70℃下搅拌一夜。向冷却的混合物中添加30mL 2NHCl溶液。然后用乙酸乙酯萃取所得的混合物。该有机层用水和盐水洗涤,在Na2SO4上干燥。在除去溶剂后,通过柱色谱法提纯该残留物,以70-80%产率得到缩合产物。
在0℃下向缩合产物(1.67mmol)、二异丙基乙胺(1.98mL,6.68mmol)和三乙胺(1.38mL,16.7mmol)在10mL CH2Cl2中的混合物中添加258μL(3.34mmol)甲磺酰氯。添加后,将所得混合物升至室温并搅拌一夜。除去溶剂。将该残留物重新溶解在乙酸乙酯中,用水和盐水洗涤,并在Na2SO4上干燥。除去溶剂后,通过柱色谱法提纯该粗产物,以70-80%产率得到纯净的4a-f。
4a:[α]20 D=-75.1°(c=0.9,CHCl3),1H NMR(360MHz,CDCl3)δ0.81(d,6.8Hz,3H),0.89(d,6.8Hz,3H),1.24(d,3JHP=16.5Hz,9H),1.58(m,1H),1.71(m,1H),1.90(m,1H),2.11(m,2H),2.37(m,2H),3.19(m,1H),3.86(m,1H),3.94(t,7.9Hz,1H),4.21(t,8.1Hz,1H);13C NMR(90MHz,CDCl3)δ18.7,19.4,25.4(m),30.6(d,2JCP=7.9Hz),31.8(d,JCP=47.5Hz),32.0,33.1,35.2(d,JCP=43.4Hz),38.8(d,JCP=39.5Hz),70.6,72.4,163.9;31P NMR(145MHz,CDCl3)δ88.0;APCI MS 288(M++H);对于C14H27NOPS的HRMS计算值288.1551,实测值288.1549。
4b:[α]20 D=-75.9°(c=0.9,CHCl3),1H NMR(360MHz,CDCl3)δ0.83(s,9H),1.25(d,3JHP=16.4Hz,9H),1.56(m,1H),1.87(m,1H),2.14(m,2H),2.38(m,2H),3.21(m,1H),3.83(m,1H),4.01(t,8.4Hz,1H),4.16(t,8.5Hz,1H);13C NMR(90MHz,CDCl3)δ25.6(d,2JCP=1.6Hz),26.5,30.6(d,2JCP=7.9Hz),31.9(d,JCP=47.2Hz),32.0,33.8,35.3(d,JCP=43.6Hz),38.9(d,JCP=40.0Hz),69.1,75.9,163.9;31P NMR(145MHz,CDCl3)δ87.3;ESI MS 302(M++H);对于C15H29NOPS的HRMS计算值302.1707,实测值302.1716。
4c:[α]20 D=-98.9°(c=1,CHCl3),1H NMR(360MHz,CDCl3)δ1.24(d,3JHP=16.6Hz,9H),1.58(m,1H),1.91(m,1H),2.16(m,2H),2.39(m,2H),3.28(m,2H),3.19(t,8.3Hz,1H),4.58(t,8.3Hz,1H),5.14(m,1H),7.19(m,5H);13C NMR(90MHz,CDCl3)δ25.0(d,2JCP=1.1Hz),30.2(d,2JCP=7.7Hz),31.3(d,JCP=47.3Hz),31.5,34.8(d,JCP=43.4Hz),38.6(d,JCP=39.2Hz),69.6,74.9,127.3(m),142.3,165.2(d,2JCP=4.6Hz);31PNMR(145MHz,CDCl3)δ88.8;APCI MS 322(M++H);对于C17H25NOPS的HRMS计算值322.1395,实测值322.1409。
4d:[α]20 D=-54.2°(c=1,CHCl3),1H NMR(360MHz,CDCl3)δ1.17(d,3JHP=16.5Hz,9H),1.52(m,1H),1.84(m,1H),2.07(m,2H),2.32(m,2H),2.58(dd,8.2Hz,13.6Hz,1H),2.98(dd,5.5Hz,13.6Hz,1H),3.06(dd,9.6Hz,17.3Hz,1H),3.88(t,7.3Hz,1H),4.09(t,8.5Hz),4.3(m,1H),7.13(m,5H);13C NMR(90MHz,CDCl3)δ24.4,24.6(d,2JCP=1.2Hz),29.8(d,2JCP=8.0Hz),30.9(d,JCP=47.4Hz),34.3(d,JCP=43.4Hz),37.8(d,JCP=39.1Hz),41.5,66.8,71.3,125.8,127.9,128.8(m),163.7(d,2JCP=4.7Hz);31P NMR(145MHz,CDCl3)δ88.5;APCI MS 336(M++H);对于C18H27NOPS的HRMS计算值336.1551,实测值336.1542。
4e:[α]20 D=-83.9°(c=1,CHCl3),1H NMR(360MHz,CDCl3)δ0.67(t,6.4Hz,6H),1.04(d,3JHP=16.4Hz,9H),1.43(m,3H),1.67(m,1H),1.94(m,2H),2.19(m,2H),3.00(m,1H),3.60(t,7.4Hz,1H),3.91(m,1H),4.08(m,8.5Hz,1H);13C NMR(90MHz,CDCl3)δ22.3,22.5,24.4,24.6,24.9,29.8(d,2JCP=7.9Hz),30.9(d,JCP=47.4Hz),31.4Hz,34.3(d,JCP=43.4Hz),37.9(d,JCP=39.4Hz),45.3,64.1,72.6,162.9(d,2JCP=4.6Hz);31P NMR(145MHz,CDCl3)δ88.0;ESI MS 302(M++H);对于C15H28NOPS的HRMS计算值302.1708,实测值302.1715。
4f:[α]20 D=+28.6°(c=0.9,CHCl3),1H NMR(360MHz,CDCl3)δ0.82(d,6.7Hz,3H),0.94(d,6.7Hz,3H),0.95(d,3JHP=16.4Hz,9H),1.58(m,1H),1.75(m,1H),1.89(m,1H),2.13(m,2H),2.39(m,2H),3.11(m,1H),3.81(m,1H),3.95(t,8.2Hz,1H),4.20(t,8.2Hz);13C NMR(90MHz,CDCl3)δ18.6,20.0,25.2,25.4(d,2JCP=1.4Hz),30.7(d,2JCP=7.8Hz),32.8(d,JCP=47.6Hz),32.0,33.2,35.1(d,JCP=43.6Hz),38.7(d,JCP=39.8Hz),70.6,72.8,163.7(d,2JCP=4.5Hz);31P NMR(145MHz,CDCl3)δ87.9;ESI MS 288(M++H);对于C14H27NOPS的HRMS计算值288.1551,实测值288.1545。
一般程序:
向N2清洗过的Schlenk烧瓶中装入5.0g阮内镍2800浆料。该阮内镍顺序地用甲醇(10mL×3)、乙醚(10mL×3)和干燥脱气的CH3CN(10mL×3)洗涤。然后由移液管向该烧瓶中转移4a-f(1.5mmol)在CH3CN(20mL)中的溶液。在N2下搅拌该混合物2天。然后在N2下过滤该混合物。该阮内镍固体用CH3CN洗涤(10mL×5)。混合的CH3CN与滤液在N2下蒸发,得到油状残留物。该残留物在氮气中通过Al2O3(碱性)管塞,得到纯净的油性产物5a-f(80-95%)。
5a:1H NMR(400MHz,CD2Cl2)δ0.88(d,6.8Hz,3H),0.94(d,6.8Hz,6.8Hz),1.08(d,3JHP=11.9Hz,9H),1.72(m,4H),2.01(b,3H),2.81(b,1H),3.85(b,1H),3.95(t,7.6Hz,1H),4.20(t,7.6Hz,1H);13C NMR(100MHz,CD2Cl2)δ18.3,18.8,23.3(d,2JCP=17.5Hz),27.6(d,2JCP=14.5Hz),29.0,29.1(d,JCP=18.4Hz),33.2(d,JCP=19.9Hz),36.9(d,JCP=20.2Hz),70.2,72.4,169.1(d,2JCP=15.9Hz);31P NMR(145MHz,CD2Cl2)δ26.0;ESI MS256(M++H);对于C14H27NOP的HRMS计算值256.1830,实测值256.1820。
5b:1H NMR(360MHz,CDCl3)δ0.71(s,9H),0.90(d,3JHP=11.9Hz,9H),1.56(m,3H),1.83(m,3H),2.73(b,1H),3.65(m),3.92(t,7.6Hz,1H),3.99(t,9.3Hz,1H);13C NMR(90MHz,CDCl3)δ21.9(d,2JCP=17.6Hz),24.8,26.4(d,2JCP=14.2Hz),27.7(d,2.84Hz),28.9(d,JCP=18.0Hz),32.4(d,JCP=70.0Hz),35.8(d,JCP=19.8Hz),67.7,74.4,168.9(d,2JCP=15.9Hz);31P NMR(145MHz,CDCl3)δ25.2;ESI MS 270(M++H);对于C15H29NOP的HRMS计算值270.1987,实测值270.1972。
5c:1H NMR(360MHz,CD2Cl2)δ0.98(d,3JHP=12.0Hz,9H),1.66(m,3H),1.92(m,3H),2.80(m,1H),3.91(t,7.9Hz,1H),4.46(dd,8.3Hz,10.0Hz,1H),5.01(m,1H),7.17(m,5H);13C NMR(90MHz,CD2Cl2)δ23.5(d,2JCP=17.6Hz),27.9(d,2JCP=14.4Hz),29.2(d,2JCP=2.1Hz),29.4(d,JCP=18.7Hz),33.4,37.1(d,JCP=20.1Hz),70.1,75.3,127.0-129.1(m),144.0,172.0(d,2JCP=15.8Hz);31P NMR(145MHz,CD2Cl2)δ27.4;ESI MS290(M++H);对于C17H24NOP的HRMS计算值290.1674,实测值290.1663。
5d:1H NMR(360MHz,CD2Cl2)δ1.06(d,3JHP=11.9Hz,9H),1.74(m,3H),2.01(m,3H),2.67(dd,7.5Hz,13.6Hz,1H),2.74(m,1H),2.96(dd,6.1Hz,13.6Hz,1H),3.92(dd,7.0Hz,8.2Hz,1H),4.17(t,9.0Hz,1H),4.30(m,1H),7.28(m,5H);13C NMR(90MHz,CD2Cl2)δ23.4(d,JCP=17.9Hz),27.8(d,2JCP=14.4Hz),29.1(d,2JCP=2.2Hz),29.3(d,JCP=18.7Hz),33.4(d,2JCP=1.2Hz),37.1(d,JCP=20.0Hz),42.5,68.0,72.2,126.8,128.9,130.0,139.2,170.9(d,2JCP=15.8Hz);31P NMR(145MHz,CD2Cl2)δ26.7;ESI MS 304(M++H);对于C18H27NOP的HRMS计算值304.1830,实测值304.1836。
5e:1H NMR(360MHz,CD2Cl2)δ0.86(d,4.3Hz,3H),0.92(d,4.3Hz,3H),1.03(d,3JHP=11.9Hz,9H),1.25(m,1H),1.49(m,1H),1.73(m,4H),1.95(m,3H),2.74(m,1H),3.75(t,7.7Hz,1H),4.03(m,1H),4.25(dd,8.0Hz,9.1Hz,1H);13C NMR(90MHz,CD2Cl2)δ23.1,23.3(d,2JCP=17.7Hz),26.0,27.8(d,2JCP=14.4Hz),29.1(d,2JCP=2.4Hz),29.2(d,JCP=18.7Hz),33.3(d,1.6Hz),37.1(d,JCP=19.9Hz),46.3,65.2,73.4,169.9(d,2JCP=15.8Hz);31P NMR(145MHz,CD2Cl2)δ26.1;ESI MS270(M++H);对于C15H28NOP的HRMS计算值270.1987,实测值270.2042。
5f:1H NMR(360MHz,CDCl3)δ0.73(d,6.8Hz,3H),0.80(d,6.8Hz,3H),0.93(d,3JHP=12.0Hz,9H),1.49(m,1H),1.66(m,3H),1.89(m,3H),2.66(m,1H),3.76(m,1H),3.84(t,7.6Hz,1H),4.07(t,8.8Hz,1H);13C NMR(90MHz,CDCl3)δ16.6,17.9,21.8(d,JCP=17.4Hz),26.5(d,2JCP=14.3Hz),27.5(d,2JCP=2.4Hz),27.8(d,JCP=18.0Hz),31.3,31.9(d,1.1Hz),35.5(d,JCP=19.8Hz),68.5,70.6,169.0(d,2JCP=15.5Hz);31PNMR(145MHz,CDCl3)δ25.9;ESI MS 256(M++H);对于C14H27NOP的HRMS计算值256.1830,实测值256.1805。
实施例9,Ir-PN化合物的制备
一般程序:
向Schlenk管中添加5a-f(0.346mmol)、[Ir(COD)Cl]2(116mg,0.173mmol)和干燥脱气的CH2Cl2(4mL)。深红色混合物在N2下加热回流1小时,直到原位31P NMR显示原料被耗尽。在反应混合物冷却到室温后,添加Na[BARF](453mg,0.519mmol),随后添加脱气H2O(5mL),剧烈搅拌所得的二相混合物30分钟。分离两层并用CH2Cl2进一步洗涤水层。混合的CH2Cl2溶液经过蒸发得到棕色残留物,随后通过Al2O3管塞(洗脱液:己烷∶CH2Cl2=1∶2)以50-70%产率得到纯的橙黄色产物6a-f。
6a:1H NMR(360MHz,CD2Cl2)δ0.74(d,6.8Hz,3H),0.91(d,7.0Hz,3H),1.17(d,3JHP=15.4Hz,9H),1.58(m,2H),1.83-2.40(m,13H),3.09(m,1H),4.13(m,3H),4.51(t,9.4Hz,1H),4.65(dd,3.8Hz,9.4Hz,1H),4.94(m,2H),7.59(s,4H),7.73(s,8H);13C NMR(90MHz,CD2Cl2)δ14.0,19.0,24.0(d,2JCP=25.6Hz),27.1(d,2JCP=3.5Hz),27.8,30.1(d,1.9Hz),31.1,32.2(d,1.9Hz),32.5(d,JCP=23.4Hz),33.9(d,2.1Hz),36.2(d,3.7Hz),37.8(d,JCP=30.0Hz),60.6,63.1,70.0,73.0,90.3(d,11.8Hz),93.5(d,10.9Hz),118.0(t),120.7,123.7,126.7,129.3(dd,28.4Hz,58.6Hz),135.4(t,92.9Hz),162.3(q,49.6Hz),190.1(d,2JCP=19.7Hz);31PNMR(145MHz,CD2Cl2)δ51.9;ESI+MS:556(阳离子+1);ESI-MS:863(阴离子);对于IrC22H39NOP的HRMS计算值556.2320,实测值556.2318;对于C32H12F24B的HRMS计算值863.0649,实测值863.0650。
6b:1H NMR(360MHz,CD2Cl2)δ0.88(s,9H),1.15(d,3JHP=15.4Hz,9H),1.43(b,2H),1.60-2.40(m,11H),2.87(d,7.6Hz,1H),3.55(m,1H),3.80(b,1H),4.38(m,2H),4.54(m,1H),4.73(dd,1.8Hz,9.8Hz),5.02(b,1H),7.48(s,4H),7.64(s,8H);13C NMR(90MHz,CD2Cl2)δ23.7,24.0,25.5,26.0,25.5,27.3(d,2JCP=3.4Hz),29.4,31.5(d,JCP=25.5Hz),34.0,34.8,35.7,37.2(d,JCP=30.3Hz),37.7,56.5,65.2,71.1,75.2,86.0(d,16.5Hz),96.0(d,8.1Hz),111.8(t),120.7,123.7,126.7,129.4(dd,28.5Hz,62.7Hz),135.4(t),162.3(q,49.4Hz),188.4(d,2JCP=17.9Hz);31PNMR(145MHz,CD2Cl2)δ42.4;ESI+MS:570(阳离子+1);对于IrC23H41NOP的HRMS计算值570.2477,实测值570.2437;对于C32H12F24B的HRMS计算值863.0649,实测值863.0633。
6c:1H NMR(360MHz,CD2Cl2)δ1.09(d,3JHP=15.5Hz,9H),1.25(m,1H),1.46(m,2H),1.80-2.40(m,11H),3.19(m,1H),3.78(m,2H),4.00(m,1H),4.46(dd,5.2Hz,9.2Hz,1H),4.81(m,1H),4.93(dd,9.4Hz,10.0Hz,1H),5.23(m,1H),7.01(m,2H),7.34(m,3H),7.48(s,4H),6.65(s,8H);13C NMR(100MHz,CD2Cl2)δ23.1(d,2JCP=26.5Hz),27.3,27.6,28.0,28.5,30.9,31.4,33.0(d,JCP=23.6Hz),33.9,35.4,37.1(d,JCP=29.9Hz),61.7,62.6,69.4,81.3,93.3(d,11.6Hz),94.2(d,13.9Hz),118.3,121.3,124.0,126.5,126.7,129.6(dd,25.2Hz,67.1Hz),130.5(m),135.6,139.2,162.5(q,49.5Hz),191.3(d,2JCP=19.8Hz);31P NMR(145MHz,CD2Cl2)δ53.7;ESI+MS:590(阳离子+1);对于IrC25H37NOP的HRMS计算值590.2164,实测值570.2120。
6d:1H NMR(360MHz,CD2Cl2)δ1.18(d,3JHP=15.5Hz,9H),1.64(m,3H),1.80-2.50(m,11H),2.61(dd,9.8Hz,14.1Hz,1H),3.06(m,2H),4.08(m,1H),4.29(m,2H),4.49(t,9.0Hz,1H),4.69(dd,2.7Hz,9.4Hz),4.98(m,1H),5.12(b,1H),7.20(m,2H),7.35(m,3H),7.57(s,4H),7.73(s,8H);13C NMR(100MHz,CD2Cl2)δ23.7(d,2JCP=24.6Hz),26.6,27.0(d,2JCP=3.7Hz),27.2,30.0(d,JCP=15.4Hz),32.1,32.3(d,6.3Hz),33.4,36.3(d,3.7Hz),36.7(d,JCP=30.1Hz),41.4,60.4,64.0,65.2,76.6,88.9(d,12.6Hz),94.3(d,10.3Hz),117.8,120.9,123.6,126.3,128.3,129.1(m),129.6,134.5,135.2,162.0(q,49.5Hz),190.1(d,2JCP=19.2Hz);31P NMR(145MHz,CD2Cl2)δ52.0;ESI+MS:604(阳离子+1);对于IrC26H39NOP的HRMS计算值604.2320,实测值604.2322。
6e:1H NMR(360MHz,CD2Cl2)δ0.93(d,6.5Hz,3H),0.97(d,6.5Hz),1.18(d,3JHP=15.5Hz,9H),1.39(m,2H),1.60(m,4H),1.80-2.50(m,11H),3.06(d,7.6Hz),3.98(m,2H),4.21(m,1H),4.56(m,2H),4.77(m,1H),5.01(m,1H),7.57(s,4H),7.73(s,8H);13C NMR(90MHz,CD2Cl2)δ21.6,23.8,23.9(d,2JCP=24.6Hz),25.8,26.5,27.1(d,2JCP=3.7Hz),27.4,30.2,32.3(d,JCP=24.1Hz),32.5,33.8,36.4(d,3.8Hz),37.0(d,JCP=30.2Hz),45.0,60.4,63.3,64.0,77.6,89.2(d,12.4Hz),64.6(d,40.9Hz),118.1(t),120.7,123.7,126.7,129.5(dd,37.7Hz,76.2Hz),135.4(t,103.7Hz),162.4(q,49.7Hz),189,5(d,2JCP=24.6Hz);31P NMR(145MHz,CDCl2)δ51.3;ESI+MS:570(阳离子+1);对于IrC23H41NOP的HRMS计算值570.2477,实测值570.2423。
6f:1H NMR(400MHz,CD2Cl2)δ0.79(d,6.8Hz,3H),1.00(d,7.1Hz,3H),1.18(d,3JHP=15.5Hz,9H),1.80-2.30(m,12H),2.40(m,2H),3.55(m,1H),4.18(m,1H),3.93(m,1H),4.46(m,1H),4.52(t,9.4Hz,1H),4.58(m,1H),4.75(dd,3.6Hz,9.7Hz,1H),5.02(m,1H),7.61(s,4H),7.77(s,8H);13C NMR(100MHz,CD2Cl2)δ14.3(d,9.6Hz),18.6(d,3.5Hz),22.6(d,2JCP=29.7Hz),27.1(d,2JCP=4.6Hz),27.6,27.7,31.5,31.8,32.5,33.5(d,JCP=21.2Hz),35.1,36.4(d,JCP=30.4Hz),62.5(d,7.5Hz),65.4,68.9,73.3,85.6(d,14.2Hz),94.9(d,8.7Hz),117.7,120.9,123.6,126.3,129.2(dd,37.2Hz,68.5Hz),135.2,162.1(q,49.7Hz),187.0(d,2JCP=20.9Hz);31P NMR(145MHz,CD2Cl2)δ60.0;ESI+MS:556(阳离子+1);ESI-MS:863(阴离子);对于IrC22H39NOP的HRMS计算值556.2320,实测值556.2309;对于C32H12F24B的HRMS计算值863.0649,实测值863.0650。
实施例10:未官能化烯烃的不对称还原
一般氢化程序:
在氮气氛围中向CH2Cl2(2mL)中的烯烃基体(0.2mmol)溶液中添加Ir配合物6(2μmol,1mol%)。然后将该溶液转移到高压釜中。该氢化在室温和50巴氢气下进行12-48小时。在小心地释放氢气后,蒸发该反应混合物。
用乙酸乙酯重新溶解残留物,随后通过短硅胶管塞以除去催化剂。
所得溶液直接用于手性GC或HPLC以测量对映异构体的过量。
甲基均二苯代乙烯的Ir-催化不对称氢化
[a]对于详细条件参见实验部分。[b]通过手性HPLC(Chiralcel OJH)测定ee。[c]通过将旋光度与报道的数据对比来确定绝对构型。
β-甲基肉桂酸酯的Ir-催化不对称氢化
[a]对于详细条件参见实验部分。[b]通过手性HPLC(Chiralcel OJH)或手性GC(Chiralselect 1000)测定ee。[c]通过将旋光度与报道的数据对比或用类似方法来确定绝对构型。
一系列(E)-α,β-不饱和酯是根据已知方法经由Heck反应来制备的:Littke,A.F.;Fu,G.C.J.Am.Chem.Soc.,2001,123,6989-7000。向Schlenk烧瓶中添加芳基卤(6.6mmol)、巴豆酸甲酯(1.40mL,13.2mmol)、Pd2(dba)2(151mg,165μmol)、Cy2NMe(1.55mL,7.26mmol)、脱气干燥的二噁烷(20mL),然后添加tBu3P(67mg,0.33mmol)。整个混合物在氮气下于室温搅拌一夜。在反应完结时,用Et2O稀释混合物,经由硅胶片过滤并充分洗涤,浓缩,并通过柱色谱法提纯以70-80%产率得到产物。
7:1H NMR(300MHz,CDCl3)δ2.62(d,1.3Hz,3H),3.78(s,3H),6.17(d,1.2Hz,1H),7.40(m,3H),7.51(m,2H);13C NMR(90MHz,CDCl3)δ18.4,51.5,117.1,126.7,128.9,129.5,142.6,156.3,167.7;APCI MS:177(M++1);对于C11H13O2的HRMS计算值177.0916,实测值177.0906。
8:1H NMR(360MHz,CDCl3)δ2.55(d,1.2Hz,3H),3.74(s,3H),6.09(d,1.2Hz,1H),7.05(m,2H),7.45(m,2H);13C NMR(90MHz,CDCl3)δ18.2,51.3,115.6(d,21.6Hz),116.8,128.8(d,32.0Hz),138.4,154.7,162.1,164.8,167.3;APCI MS:195(M++1);对于C11H12O2F的HRMS计算值195.0821,实测值195.0824。
9:1H NMR(300MHz,CDCl3)δ2.58(d,1.3Hz,3H),3.78(s,3H),6.14(dd,1.2Hz,2.4Hz,1H),7.38(m,4H);13C NMR(75MHz,CDCl3)δ18.3,51.6,117.5,128.0,129.1,135.5,140.9,154.8,167.5;APCI MS:211(M++1);对于C11H12O2Cl的HRMS计算值211.0526,实测值211.0519。
10:1H NMR(300MHz,CDCl3)δ2.40(s,3H),2.61(d,1.2Hz,3H),3.79(s,3H),6.17(d,1.2Hz,1H),7.21(d,8.0Hz,2H),7.42(d,8.0Hz,2H);13C NMR(75MHz,CDCl3)δ18.3,21.6,51.5,116.2,126.7,129.6,139.6,156.2,167.8;APCI MS:191(M++1);对于C12H15O2的HRMS计算值191.1072,实测值191.1058。
11:1H NMR(360MHz,CDCl3)δ2.59(d,1.2Hz,3H),3.79(s,3H),6.15(d,1.2Hz,1H),7.24(d,8.1Hz,2H),2.55(dd,2.0Hz,7.9Hz);13CNMR(90MHz,CDCl3)δ18.1,51.3,117.7,119.2,121.0,121.1,128.0,140.9,149.9,154.3,167.1;
12:1H NMR(300MHz,CDCl3)δ2.58(d,1.2Hz,3H),3.74(s,3H),3.81(s,3H),6.13(dd,1.1Hz,2.4Hz,1H),6.89(dd,2.1Hz,6.8Hz,2H),7.45(dd,2.1Hz,6.8Hz,2H);13C NMR(75MHz,CDCl3)δ18.0,51.4,55.7,114.2,115.2,134.5,155.6,160.9,167.8;APCI MS:207(M++1);对于C12H15O3的HRMS计算值207.1021,实测值207.1023。
13:1H NMR(360MHz,CDCl3)δ2.40(s,3H),2.60(d,1.0Hz,3H),3.78(s,3H),6.16(d,1.0Hz,1H),7.21(m,1H),7.29(m,3H);13CNMR(90MHz,CDCl3)δ18.2,21.6,51.2,116.8,123.6,127.2,128.6,130.0,138.3,142.4,156.3,167.5;ESI MS:191(M++1);对于C12H15O2的HRMS计算值191.1072,实测值191.1091。
14:1H NMR(360MHz,CDCl3)δ2.68(s,3H),3.83(s,3H),6.04(s,1H),7.32(m,1H),7.53(m,3H),7.90(m,3H);13C NMR(90MHz,CDCl3)δ21.9,51.3,120.4,124.4,125.4,126.2,126.5,128.4,128.7,130.3,133.9,142.2,157.6,167.2;ESI MS:227(M++1);对于C15H15O2的HRMS计算值227.1072,实测值227.1066。
15:1H NMR(300MHz,CDCl3)δ2.74(s,3H),3.82(s,3H),6.33(s,1H),7.56(m,3H),7.90(m,4H);13C NMR(75MHz,CDCl3)δ18.4,51.6,117.5,124.4,126.4,127.0,127.2,128.0,128.6,128.9,133.5,133.9,139.6,156.1,167.7;APCI MS:227(M++1);对于C15H15O2的HRMS计算值227.1072,实测值227.1064。
新型氢化产物的分析数据和GC或HPLC条件
7的氢化产物:
98%ee;[α]20 D=-15.5°(c=0.7,CHCl3);手性HPLC:Chiralcel OJH,hex∶iPr=95∶5,tR=7.9min(R),9.0min(S);1H NMR(300MHz,CDCl3)δ1.33(d,7.0Hz,3H),2.58(dd,8.2Hz,15.1Hz,1H),2.66(dd,6.9Hz,15.1Hz,1H),3.30(s,3H),7.31(m,5H);13C NMR(75MHz,CDCl3)δ22.2,36.9,43.2,51.9,126.8,127.1,128.9,146.1,173.3;APCI MS:196(M++NH4 +);对于C11H18NO2的HRMS计算值196.1338,实测值196.1335。
8的氢化产物:
95%ee;[α]20 D=-1.9°(c=0.5,CHCl3);手性GC:Chiralselect 1000,140℃,tR=19.3min(S),19.9(R);1H NMR(400MHz,CDCl3)δ1.31(d,7.0Hz,3H),2.60(m,2H),3.30(m,1H),3.64(s,3H),7.16(d,8.0Hz,2H),7.27(m,2H);13C NMR(100MHz,CDCl3)δ22.2,36.2,43.0,51.9,121.4,128.4,144.7,148.1,172.9;APCI MS:214(M++NH4 +);对于C11H17FNO2的HRMS计算值214.1243,实测值214.1248。
9的氢化产物:
98%ee;[α]20 D=-32.4°(c=1.1,CHCl3);手性GC:Chiralselect 1000,140℃,tR=53.7min(S),55.5min(R);1H NMR(300MHz,CDCl3)δ1.29(d,7.0Hz,3H),2.58(m,2H),3.29(m,1H),3.63(s,3H),7.17(m,2H),7.27(m,2H);13C NMR(75MHz,CDFCl3)δ22.2,36.3,43.0,52.0,128.5,129.0,132.4,144.5,173.0;APCI MS:230(M++NH4 +);对于C11H17ClNO2的HRMS计算值230.0948,实测值230.0942。
10的氢化产物:
97%ee;[α]20 D=-2.4°(c=0.3,CHCl3);手性GC:Chiralselect 1000,140℃,tR=27.1min(S),27.7min(R);1H NMR(400MHz,CDCl3)δ1.31(d,7.0Hz,3H),2.35(s,3H),2.56(dd,8.2Hz,15.1Hz,1H),2.64(dd,7.0Hz,15.1Hz,1H),3.29(m,1H),3.66(s,3H),7.14(s,4H);13C NMR(100MHz,CDCl3)δ21.4,22.3,36.4,43.2,51.9,127.0,129.6,136.3,143.1,173.3;ESI MS:210(M++NH4 +);对于C12H20NO2的HRMS计算值210.1494,实测值210.1479。
11的氢化产物:
97%ee;[α]20 D=-23.4°(c=0.3,CHCl3);手性GC:Chiralselect 1000,140℃,tR=20.0min(S),20.5min(R);1H NMR(400MHz,CDCl3)δ1.30(d,7.0Hz,3H),2.58(m,2H),3.29(m,1H),3.66(s,3H),6.99(m,2H),7.20(m,2H);13C NMR(100MHz,CDCl3)δ22.4,36.2,43.2,51.9,115.5,128.5,141.7,160.6,163.1,173.1;ESI MS:280(M++NH4 +);对于C12H17F3NO3的HRMS计算值280.1161,实测值280.1173。
12的氢化产物:
97%ee;[α]20 D=-23.8°(c=0.7,CHCl3);手性HPLC:Chiralcel OJH,hex∶IPr=95∶5,tR=12.1min(R),13.9min(S);1H NMR(360MHz,CDCl3)δ1.27(d,7.5Hz,3H),2.52(dd,8.0Hz,15.0Hz,1H),2.59(dd,7.1Hz,15.0Hz,1H),3.61(s,3H),3.78(s,3H),6.83(m,2H),7.15(m,2H);13C NMR(90MHz,CDCl3)δ22.1,35.9,43.2,51.6,55.4,114.1,127.8,138.1,158.3,173.1;ESI MS:226(M++NH4 +);对于C12H20NO3的HRMS计算值226.1443,实测值226.1425。
13的氢化产物:
99%ee;[α]20 D=-20.2°(c=0.5,CHCl3);手性GC:Chiralselect1000,140℃,tR=47.0min(S),48.0min(R);1H NMR(360MHz,CDCl3)δ1.31(d,7.0Hz,3H),2.35(s,3H),2.52(dd,8.4Hz,15.2Hz,1H),2.64(dd,6.7Hz,15.1Hz,1H),3.25(m,1H),3.65(s,3H),7.04(m,3H),7.21(m,1H);13C NMR(90MHz,CDCl3)δ21.6,22.0,35.5,36.5,42.9,51.6,123.9,127.4,127.7,128.6,138.2,145.9,173.1;ESI MS:210(M++NH4 +);对于C12H20NO2的HRMS计算值210.1494,实测值210.1479。
14的氢化产物:
98%ee;[α]20 D=+1.8°(c=0.72,CHCl3);手性HPLC:Chiralcel OJH,hex∶iPr=99∶1,tR=32.2min(R),36.5min(S);1H NMR(400MHz,CDCl3)δ1.48(d,6.9Hz,3H),2.67(dd,9.3Hz,15.3Hz,1H),2.89(dd,5.3Hz,15.3Hz,1H),3.70(s,3H),4.21(m,1H),7.50(m,4H),7.77(d,8.0Hz,1H),7.90(d,8.0Hz,1H),8.22(d,8.4Hz,1H);13C NMR(100MHz,CDCl3)δ21.6,31.2,42.7,51.9,122.7,123.4,125.9,126.5,127.4,129.4,131.5,134.4,142.1,173.5;ESI MS:246(M++NH4 +);对于C15H20NO2的HRMS计算值246.1494,实测值246.1497。
15的氢化产物:
95%ee;[α]20 D=-40.2°(c=1.2,CHCl3);chiral HPLC:Chiralcel OJH,hex∶iPr=99∶1,tR=65.2min(R),70.9min(S);1H NMR(300MHz,CDCl3)δ1.43(d,7.0Hz,3H),2.68(dd,8.1Hz,15.2Hz,1H),2.78(dd,7.0Hz,15.2Hz,1H),3.49(m,1H),3.65(s,3H),7.46(m,3H),7.69(s,1H),7.83(m,2H);13C NMR(75MHz,CDCl3)δ22.2,37.0,43.1,52.0,125.4,125.8,125.9,126.4,128.0,128.1,128.6,132.8,134.0,143.6,173.3;ESI MS:246(M++NH4 +);对于C15H20NO2的HRMS计算值246.1494,实测值246.1481。
实施例10:下列双膦的合成和结构:
TangPhos型配体的合成和应用
按照上文所述的程序制备具有以下结构的手性双膦:
获得了相应双膦硫化物的X射线结构并显示如下:
其他应用
具有这种配体的Rh-化合物是使烯酰胺(例如PhCH(NHAc)CHCOOEt的E/Z混合物)氢化以制备β氨基酸(已经达到高达99%的ee)的有效催化剂。
已经特别地参照优选实施方案对本发明作了描述。应该理解的是前面的叙述和实施例仅仅为了举例说明本发明而已。在不偏离本发明的精神和范围的前提下,本技术领域技术人员可以设计出本发明的多种替换方案和改进方案。因此,本发明希望包括落入所附权利要求范围内的所有这类替换方案、改进方案和变体形式。
Claims (7)
3.制备(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的方法,该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生所述1-烷基-磷杂戊环-1-硫化物的阴离子;和
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使所述1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物。
4.根据权利要求3的方法,其中所述烷基是叔丁基。
5.根据权利要求3的方法,还包括以下步骤:
从所述反应混合物中重结晶该(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物。
6.制备(1S,1S’,2R,2R’)-1,1’-二-烷基-[2,2’]-联磷杂戊环的方法,该方法包括以下步骤:
在溶剂中用正丁基锂/(-)-金雀花碱使1-烷基-磷杂戊环-1-硫化物不对称地去质子化来产生1-烷基-磷杂戊环-1-硫化物的阴离子;
将1-烷基-磷杂戊环-1-硫化物的阴离子和CuCl2接触以使所述的1-烷基-磷杂戊环-1-硫化物的阴离子氧化偶合并产生包含(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物的反应混合物;
从所述反应混合物中重结晶(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物;和
将(1R,1R’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环-1,1’-二硫化物和六氯乙硅烷在溶剂中接触,以产生(1S,1S’,2R,2R’)-1,1’-二烷基-[2,2’]-联磷杂戊环。
7.根据权利要求6的方法,其中所述烷基是叔丁基。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33693901P | 2001-11-09 | 2001-11-09 | |
US60/336,939 | 2001-11-09 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN028260295A Division CN1608074B (zh) | 2001-11-09 | 2002-11-08 | P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN101565435A true CN101565435A (zh) | 2009-10-28 |
Family
ID=23318385
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2009101377911A Pending CN101565435A (zh) | 2001-11-09 | 2002-11-08 | P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 |
CN028260295A Expired - Lifetime CN1608074B (zh) | 2001-11-09 | 2002-11-08 | P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN028260295A Expired - Lifetime CN1608074B (zh) | 2001-11-09 | 2002-11-08 | P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 |
Country Status (8)
Country | Link |
---|---|
US (1) | US7105702B2 (zh) |
EP (1) | EP1451133B1 (zh) |
JP (1) | JP4488739B2 (zh) |
CN (2) | CN101565435A (zh) |
AU (1) | AU2002363788A1 (zh) |
CA (1) | CA2466449C (zh) |
ES (1) | ES2654530T3 (zh) |
WO (1) | WO2003042135A2 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102304149A (zh) * | 2011-06-28 | 2012-01-04 | 中国原子能科学研究院 | 三异丁基硫化膦的合成方法 |
CN102320908A (zh) * | 2011-06-17 | 2012-01-18 | 中山大学 | 一种β-氨基酸或其衍生物的制备方法 |
CN104892496A (zh) * | 2015-06-19 | 2015-09-09 | 武汉大学 | 一种2-吡啶酮类化合物的不对称催化氢化方法 |
CN109096338A (zh) * | 2018-09-10 | 2018-12-28 | 中国科学院上海有机化学研究所 | 苯并氮杂磷杂茂膦氧配体及含其络合物、制备方法和应用 |
CN113788858A (zh) * | 2021-08-27 | 2021-12-14 | 万华化学集团股份有限公司 | 一种用于催化烯醇氢甲酰化反应制备线性二元醇的配体及其制备方法和用途 |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7169953B2 (en) * | 2001-11-09 | 2007-01-30 | The Penn State Research Foundation | P-chiral phospholanes and phosphocyclic compounds and their use in asymmetric catalytic reactions |
ES2279198T3 (es) * | 2002-11-29 | 2007-08-16 | F. Hoffmann-La Roche Ag | Ligandos de fosfina quiral-c,p bidentados. |
CA2565130C (en) | 2003-05-02 | 2011-03-15 | Kamaluddin Abdur-Rashid | Transfer hydrogenation processes and catalysts |
WO2005010013A1 (ja) * | 2003-07-28 | 2005-02-03 | Nippon Chemical Industrial Co., Ltd. | 新規光学活性リンキラルジホスフェタン化合物、該化合物の中間体、及び該化合物を配位子とする遷移金属錯体 |
JP5122956B2 (ja) * | 2004-08-27 | 2013-01-16 | ザ ダウ ケミカル カンパニー | 不斉化触媒反応用の新規なジアザホスホラン配位子 |
JP4496100B2 (ja) * | 2005-01-31 | 2010-07-07 | 独立行政法人科学技術振興機構 | 光学活性ホスホラン化合物とその製造方法並びに不斉反応用配位子とこれを用いた不斉反応方法 |
WO2006104120A1 (ja) * | 2005-03-29 | 2006-10-05 | Meiji Seika Kaisha Ltd. | L-2-アミノ-4-(ヒドロキシメチルホスフィニル)-ブタン酸の製造法 |
EP1945650A1 (en) | 2005-11-02 | 2008-07-23 | F.Hoffmann-La Roche Ag | Bidentate c, p chiral phosphine ligands |
DE102006017588A1 (de) * | 2006-04-13 | 2007-10-18 | Wacker Chemie Ag | Hydrosilylierungsverfahren in Gegenwart von Ruthenium-Katalysatoren |
CN101484414B (zh) * | 2006-07-06 | 2012-11-21 | 巴斯夫欧洲公司 | 制备旋光3-氨基羧酸酯的方法 |
JP2008110920A (ja) * | 2006-10-27 | 2008-05-15 | Takasago Internatl Corp | 光学活性ホスフィン化合物及びそれを用いた不斉反応 |
CN101565366B (zh) * | 2008-04-25 | 2013-04-17 | 浙江九洲药业股份有限公司 | 铱络合物在不饱和羧酸不对称催化氢化中的应用 |
US20100217013A1 (en) * | 2008-12-15 | 2010-08-26 | Wenge Li | Enantioselective process for the preparation of zolmitriptan |
JP5803042B2 (ja) * | 2010-04-05 | 2015-11-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | クロスカップリング反応におけるモノリン配位子及びそれらの使用 |
ES2686298T3 (es) | 2010-04-20 | 2018-10-17 | Chiral Quest, Inc. | Procedimiento enantioselectivo para alaninas beta sustituidas con cicloalquenilo |
CN106146351B (zh) * | 2015-04-03 | 2020-09-11 | 博瑞生物医药(苏州)股份有限公司 | 制备联芳基取代的4-氨基-丁酸或其衍生物的方法 |
CN111018918B (zh) * | 2018-10-10 | 2022-10-04 | 中国科学院上海有机化学研究所 | 一种金属配合物、中间体、其制备方法及应用 |
CN109503660B (zh) * | 2018-12-25 | 2020-12-22 | 华东师范大学 | 一类环状膦骨架的手性单膦催化剂Le-Phos及其全构型的制备方法和应用 |
GB201900253D0 (en) * | 2019-01-08 | 2019-02-27 | Univ Court Univ St Andrews | Catalysts and uses thereof |
CN109912508B (zh) * | 2019-04-30 | 2022-08-12 | 上海天慈国际药业有限公司 | 一种右美托咪定及其盐酸盐的制备方法 |
CN114436831A (zh) * | 2020-11-02 | 2022-05-06 | 中国科学院大连化学物理研究所 | 一种手性1-乙酸苯丙酯类化合物的合成方法 |
CN114213463A (zh) * | 2022-01-11 | 2022-03-22 | 凯美克(上海)医药科技有限公司 | 一种含有五价磷中心的氮磷杂环的合成方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5149878A (en) * | 1988-03-28 | 1992-09-22 | Robertson Allan J | 1,4-disubstituted-2,3,5,6-tetrahyddroxy-1,4-diphosphorinanes and their oxides or sulfides |
SG30598G (en) * | 1990-05-17 | 1995-09-01 | Du Pont | Chiral phospholane transition metal catalysts |
CA2254140A1 (en) * | 1996-07-15 | 1998-01-22 | Ulrich Berens | Ligands for asymmetric catalysis |
DE19725796A1 (de) * | 1997-06-18 | 1998-12-24 | Basf Ag | Herstellung optisch aktiver Phospholane, deren Metallkomplexe und Anwendung in der asymmetrischen Synthese |
US6545183B1 (en) * | 1997-11-07 | 2003-04-08 | Chirotech Technology Limited | Process for preparing cyclic phosphines |
EP1341799B1 (en) * | 2000-12-13 | 2005-03-16 | Warner-Lambert Company LLC | P-chirale bisphospholane ligands, their transition metal complexes |
DE10100971A1 (de) * | 2001-01-11 | 2002-07-18 | Degussa | Verfahren zur Herstellung enantiomerenangereicherter beta-Aminosäure |
US7169953B2 (en) * | 2001-11-09 | 2007-01-30 | The Penn State Research Foundation | P-chiral phospholanes and phosphocyclic compounds and their use in asymmetric catalytic reactions |
-
2002
- 2002-11-08 JP JP2003543975A patent/JP4488739B2/ja not_active Expired - Fee Related
- 2002-11-08 AU AU2002363788A patent/AU2002363788A1/en not_active Abandoned
- 2002-11-08 EP EP02803182.1A patent/EP1451133B1/en not_active Expired - Lifetime
- 2002-11-08 WO PCT/US2002/035788 patent/WO2003042135A2/en active Application Filing
- 2002-11-08 CN CNA2009101377911A patent/CN101565435A/zh active Pending
- 2002-11-08 US US10/291,232 patent/US7105702B2/en not_active Expired - Lifetime
- 2002-11-08 ES ES02803182.1T patent/ES2654530T3/es not_active Expired - Lifetime
- 2002-11-08 CN CN028260295A patent/CN1608074B/zh not_active Expired - Lifetime
- 2002-11-08 CA CA2466449A patent/CA2466449C/en not_active Expired - Lifetime
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102320908A (zh) * | 2011-06-17 | 2012-01-18 | 中山大学 | 一种β-氨基酸或其衍生物的制备方法 |
CN102304149A (zh) * | 2011-06-28 | 2012-01-04 | 中国原子能科学研究院 | 三异丁基硫化膦的合成方法 |
CN102304149B (zh) * | 2011-06-28 | 2013-12-25 | 中国原子能科学研究院 | 三异丁基硫化膦的合成方法 |
CN104892496A (zh) * | 2015-06-19 | 2015-09-09 | 武汉大学 | 一种2-吡啶酮类化合物的不对称催化氢化方法 |
CN109096338A (zh) * | 2018-09-10 | 2018-12-28 | 中国科学院上海有机化学研究所 | 苯并氮杂磷杂茂膦氧配体及含其络合物、制备方法和应用 |
CN109096338B (zh) * | 2018-09-10 | 2020-05-12 | 中国科学院上海有机化学研究所 | 苯并氮杂磷杂茂膦氧配体及含其络合物、制备方法和应用 |
CN113788858A (zh) * | 2021-08-27 | 2021-12-14 | 万华化学集团股份有限公司 | 一种用于催化烯醇氢甲酰化反应制备线性二元醇的配体及其制备方法和用途 |
CN113788858B (zh) * | 2021-08-27 | 2023-08-11 | 万华化学集团股份有限公司 | 一种用于催化烯醇氢甲酰化反应制备线性二元醇的配体及其制备方法和用途 |
Also Published As
Publication number | Publication date |
---|---|
CN1608074B (zh) | 2011-09-07 |
WO2003042135A3 (en) | 2003-12-24 |
AU2002363788A1 (en) | 2003-05-26 |
EP1451133A2 (en) | 2004-09-01 |
JP4488739B2 (ja) | 2010-06-23 |
JP2005509012A (ja) | 2005-04-07 |
US7105702B2 (en) | 2006-09-12 |
US20030144137A1 (en) | 2003-07-31 |
EP1451133A4 (en) | 2006-07-19 |
CA2466449C (en) | 2014-03-25 |
CN1608074A (zh) | 2005-04-20 |
EP1451133B1 (en) | 2017-10-25 |
CA2466449A1 (en) | 2003-05-22 |
WO2003042135A2 (en) | 2003-05-22 |
ES2654530T3 (es) | 2018-02-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1608074B (zh) | P-手性磷杂戊环和磷环化合物及其在不对称催化反应中的用途 | |
US7153809B2 (en) | P-chiral phospholanes and phosphocyclic compounds and their use in asymmetric catalytic reactions | |
CN102177170B (zh) | 具有三齿配体的新型羰基钌配合物、其制备方法和用途 | |
JP4167899B2 (ja) | オルト置換キラルホスフィンおよびホスフィナイトならびに非対称触媒反応でのその使用 | |
JP4754753B2 (ja) | キラルフェロセンホスフィン及び不斉触媒反応におけるその使用 | |
US5767276A (en) | Asymmetric synthesis catalyzed by transition metal complexes with new chiral ligands | |
KR100384411B1 (ko) | 키랄리간드인헤테로방향족디포스핀 | |
JP4837857B2 (ja) | キラル配位子、その遷移金属錯体および不斉反応におけるその使用 | |
JP3204667B2 (ja) | キラルなホスフイン | |
WO2006028977A2 (en) | Chiral spiro compounds and their use in asymmetric catalytic reactions | |
WO2001000581A1 (en) | Ligands based on chiral 2-amino-2'-hydroxy-1,1'-binaphthyl and related frameworks for asymmetric catalysis | |
CA2380566C (en) | Novel chiral phosphorus ligands and the use thereof in the production of optically active products | |
Paule et al. | Synthesis and Molecular Modeling Studies of SYNPHOS®, a New, Efficient Diphosphane Ligand For Ruthenium‐Catalyzed Asymmetric Hydrogenation | |
EP0732337B1 (en) | Optically active asymmetric diphosphine and process for producing optically active substance in its presence | |
US20040072680A1 (en) | Chiral phosphorus cyclic compounds for transition metal-catalyzed asymmetric reactions | |
EP1844061A1 (en) | Metallocene-based phosphorus chiral phosphines | |
JPH10130286A (ja) | 新規光学活性ジホスフィン及び該化合物より得られる遷移金属錯体及び該錯体の存在下にて光学活性体を得る方法 | |
Wang et al. | Preparation of C2‐Symmetric Bis [2‐(diphenylphosphino) ferrocen‐1‐yl]‐methane and Its Use in Rhodium‐and Ruthenium‐Catalyzed Hydrogenation | |
KR20010031959A (ko) | 강성 키랄 리간드를 포함하는 비대칭 합성용 촉매 | |
WO2003099745A1 (en) | Process for the preparation of enantiomerically enriched compounds | |
Yang | Design, syntheses and applications of chiral transition metal complexes bearing phosphorus-containing ligands | |
MXPA00004629A (en) | Catalysts for asymmetric syntheses containing rigid chiral ligands |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20091028 |