ITMI20011322A1 - MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES - Google Patents
MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES Download PDFInfo
- Publication number
- ITMI20011322A1 ITMI20011322A1 IT2001MI001322A ITMI20011322A ITMI20011322A1 IT MI20011322 A1 ITMI20011322 A1 IT MI20011322A1 IT 2001MI001322 A IT2001MI001322 A IT 2001MI001322A IT MI20011322 A ITMI20011322 A IT MI20011322A IT MI20011322 A1 ITMI20011322 A1 IT MI20011322A1
- Authority
- IT
- Italy
- Prior art keywords
- chiral
- aminophosphites
- aryl
- scheme
- group
- Prior art date
Links
- 229910052751 metal Inorganic materials 0.000 title claims description 10
- 239000002184 metal Substances 0.000 title claims description 10
- 238000007172 homogeneous catalysis Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000003054 catalyst Substances 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 21
- 239000003446 ligand Substances 0.000 claims description 20
- SJDGTRIOQBZYSU-UHFFFAOYSA-N NP(O)(O)O Chemical class NP(O)(O)O SJDGTRIOQBZYSU-UHFFFAOYSA-N 0.000 claims description 17
- 230000009467 reduction Effects 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000012298 atmosphere Substances 0.000 claims description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 9
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical group PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 150000001414 amino alcohols Chemical class 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 229910052723 transition metal Inorganic materials 0.000 claims description 7
- 150000003624 transition metals Chemical class 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical group OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- -1 aliphatic aromatic hydrocarbons Chemical class 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- DVWQNBIUTWDZMW-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalen-2-ol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=CC=CC2=C1 DVWQNBIUTWDZMW-UHFFFAOYSA-N 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- NMRIWJZVFRZDSS-UHFFFAOYSA-N amino dihydrogen phosphite Chemical class NOP(O)O NMRIWJZVFRZDSS-UHFFFAOYSA-N 0.000 claims description 2
- 150000004696 coordination complex Chemical class 0.000 claims description 2
- LWNLXVXSCCLRRZ-UHFFFAOYSA-N dichlorophosphane Chemical compound ClPCl LWNLXVXSCCLRRZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- VYXHVRARDIDEHS-QGTKBVGQSA-N (1z,5z)-cycloocta-1,5-diene Chemical compound C\1C\C=C/CC\C=C/1 VYXHVRARDIDEHS-QGTKBVGQSA-N 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 125000004437 phosphorous atom Chemical group 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 3
- XODAOBAZOQSFDS-JXMROGBWSA-N (e)-2-acetamido-3-phenylprop-2-enoic acid Chemical compound CC(=O)N\C(C(O)=O)=C\C1=CC=CC=C1 XODAOBAZOQSFDS-JXMROGBWSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000370 acceptor Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 150000002081 enamines Chemical class 0.000 description 3
- 238000007037 hydroformylation reaction Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 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 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CBQJSKKFNMDLON-JTQLQIEISA-N N-acetyl-L-phenylalanine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CBQJSKKFNMDLON-JTQLQIEISA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
- 239000012965 benzophenone Substances 0.000 description 2
- 150000005347 biaryls Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000000879 imine group Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- GVVCHDNSTMEUCS-UAFMIMERSA-N (2r,5r)-1-[2-[(2r,5r)-2,5-diethylphospholan-1-yl]phenyl]-2,5-diethylphospholane Chemical compound CC[C@@H]1CC[C@@H](CC)P1C1=CC=CC=C1P1[C@H](CC)CC[C@H]1CC GVVCHDNSTMEUCS-UAFMIMERSA-N 0.000 description 1
- IZFHMLDRUVYBGK-UHFFFAOYSA-N 2-methylene-3-methylsuccinic acid Chemical compound OC(=O)C(C)C(=C)C(O)=O IZFHMLDRUVYBGK-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229910019032 PtCl2 Inorganic materials 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- HRJABHWZEQHPFS-UHFFFAOYSA-N [1-[2-(12,14-dioxa-13-phosphapentacyclo[13.8.0.02,11.03,8.018,23]tricosa-1(15),2(11),3,5,7,9,16,18,20,22-decaen-13-yloxy)naphthalen-1-yl]naphthalen-2-yl]-diphenylphosphane Chemical compound O1C=2C=CC3=CC=CC=C3C=2C(C2=CC=CC=C2C=C2)=C2OP1OC1=CC=C2C=CC=CC2=C1C(C1=CC=CC=C1C=C1)=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 HRJABHWZEQHPFS-UHFFFAOYSA-N 0.000 description 1
- WHLQQRGHOPIIMQ-UHFFFAOYSA-N [2-(2-diphenylphosphanyl-6-methylphenyl)-3-methylphenyl]-diphenylphosphane Chemical compound CC=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=1C(C)=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 WHLQQRGHOPIIMQ-UHFFFAOYSA-N 0.000 description 1
- BFJVWYAENGOFFP-UHFFFAOYSA-N [3-(2-diphenylphosphanyl-1-benzothiophen-3-yl)-1-benzothiophen-2-yl]-diphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=C(C=2C3=CC=CC=C3SC=2P(C=2C=CC=CC=2)C=2C=CC=CC=2)C2=CC=CC=C2S1 BFJVWYAENGOFFP-UHFFFAOYSA-N 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000006717 asymmetric allylation reaction Methods 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- FWXAUDSWDBGCMN-ZEQRLZLVSA-N chiraphos Chemical compound C=1C=CC=CC=1P([C@@H](C)[C@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-ZEQRLZLVSA-N 0.000 description 1
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 1
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 1
- KZRJKMZQXATVEB-UHFFFAOYSA-N chlorophosphinous acid Chemical compound OPCl KZRJKMZQXATVEB-UHFFFAOYSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- QKZWXPLBVCKXNQ-ROJLCIKYSA-N dipamp Chemical compound COC1=CC=CC=C1[P@@](C=1C=CC=CC=1)CC[P@@](C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-ROJLCIKYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical class [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005669 hydrocyanation reaction Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 150000002503 iridium Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical class OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- USKHBABPFFAKJD-UHFFFAOYSA-N methyl 2-acetamido-3-phenylprop-2-enoate Chemical compound COC(=O)C(NC(C)=O)=CC1=CC=CC=C1 USKHBABPFFAKJD-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 125000005538 phosphinite group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Descrizione del brevetto per invenzione industriale avente per titolo: Description of the patent for industrial invention entitled:
“AMMINOFOSFITI A CHIRALITÀ MISTA IN QUALITÀ DI LEGANTI CHIRALI PER LA CATALISI OMOGENEA STEREOCONTROLLATA CON COMPLESSI DI METALLI DI TRANSIZIONE” "MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL BINDERS FOR STEREOCONTROLLED HOMOGENEOUS CATALYSIS WITH TRANSITION METAL COMPLEXES"
Stato dell’arte State of the art
Come è noto le reazioni stereoselettive rivestono una importanza sempre più rilevante in molti campi della chimica fine, dall’ industria farmaceutica a quella dei profumi, dalla chimica degli antiparassitari a quella degli additivi alimentari. Tra gli esempi di reazioni stereoselettive, le riduzioni stereocontrollate come le idrogenazioni enantio e diastereoselettive di substrati prochirali olefinici, chetonici, imminici o enamminici rappresentano un settore caratterizzato da grandi investimenti in ricerca e sviluppo. La ragione principale è legata al fatto che tali reazioni portano alla formazione di composti otticamente attivi che altrimenti sarebbero preparati sotto forma di racemi. La produzione di un racemo presenta, com’è noto, la necessità di separare gli enantiomeri, con tutti i problemi e le difficoltà che tale processo può comportare. Non va dimenticato inoltre che nella sintesi di un racemo e nell’isolamento dell’enantiomero puro, nella migliore delle ipotesi il 50% del prodotto deve essere scartato se non è possibile riconvertirlo e riciclarlo. As is well known, stereoselective reactions play an increasingly important role in many fields of fine chemistry, from the pharmaceutical industry to that of perfumes, from the chemistry of pesticides to that of food additives. Among the examples of stereoselective reactions, stereocontrolled reductions such as the enantio and diastereoselective hydrogenations of olefinic, ketone, imine or enamine prochiral substrates represent a sector characterized by large investments in research and development. The main reason is related to the fact that these reactions lead to the formation of optically active compounds that would otherwise be prepared in the form of racemes. The production of a raceme presents, as is known, the need to separate the enantiomers, with all the problems and difficulties that this process can entail. It should also not be forgotten that in the synthesis of a raceme and in the isolation of the pure enantiomer, at best 50% of the product must be discarded if it is not possible to reconvert and recycle it.
Le riduzioni stereocontrollate vengono generalmente realizzate utilizzando catalizzatori chirali a base di metalli di transizione con leganti otticamente attivi: questa tecnica permette di ottenere prodotti anch’essi otticamente attivi, spesso con alti eccessi enantiomerici e notevole chemo- e regioselettività. Stereocontrolled reductions are generally made using transition metal-based chiral catalysts with optically active ligands: this technique allows to obtain optically active products, often with high enantiomeric excesses and considerable chemo- and regioselectivity.
Anche se i primi esempi di idrogenazione stereocontrollata in fase eterogenea risalgono agli anni trenta del secolo scorso (si prevedeva l’utilizzo di metalli finemente suddivisi depositati su matrici chirali), lo sviluppo e le possibilità applicative dell’idrogenazione catalitica stereocontrollata sono diventate realtà con lo sviluppo di catalizzatori a base di metalli di transizione con fosfine chirali stabilmente coordinate al metallo, in grado di idrogenare in fase omogenea, i metalli preferiti essendo soprattutto quelli dell’ottavo gruppo a basso stato di ossidazione, come Ru(II),Rh(I),Pd(II), Pt(II), Ir(I) con leganti fosfinici caratterizzati dalla presenza di uno o più atomi di carbonio o di fosforo stereogenici. Although the first examples of stereocontrolled hydrogenation in the heterogeneous phase date back to the 1930s (the use of finely divided metals deposited on chiral matrices was foreseen), the development and application possibilities of stereocontrolled catalytic hydrogenation have become reality with the development of catalysts based on transition metals with chiral phosphines stably coordinated to the metal, capable of hydrogenating in a homogeneous phase, the preferred metals being above all those of the eighth group with a low oxidation state, such as Ru (II), Rh (I ), Pd (II), Pt (II), Ir (I) with phosphine ligands characterized by the presence of one or more stereogenic carbon or phosphorus atoms.
Tra i leganti più noti si deve ricordare innanzitutto il capostipite di tutta la famiglia dei leganti difosfinici chelanti chirali: il DIOP il cui enantiomero (+)-(4S,5S) presenta la formula qui sotto riportata [H. Kagan, in “Comprehensive Organometallic Chemistry”, G. Wilkinson, ed. 8, eh. 53, (1982) Pergamon Press, Oxford]; un altro legante di notevole successo è il CHIRAPHOS (2S,3S) [M.D.Fryzuk et al., J.Am.Chem.Soc. 99,6262,(1977)]: Among the best known ligands, the progenitor of the whole family of chiral chelating diphosphinic ligands must first be mentioned: DIOP whose enantiomer (+) - (4S, 5S) has the formula below [H. Kagan, in “Comprehensive Organometallic Chemistry”, G. Wilkinson, ed. 8, huh. 53, (1982) Pergamon Press, Oxford]; another very successful ligand is CHIRAPHOS (2S, 3S) [M.D.Fryzuk et al., J.Am.Chem.Soc. 99,6262, (1977)]:
Tra le difosfine caratterizzate dalla presenza di atomi di fosforo stereogenici, di formula RR’R”P, il più noto è lo (R,R)- DIPAMP [B.D.Vineyard et al.J.Am.Chem.Soc. 99,5946,(1977)]. Un altro tipo di leganti fosfinici otticamente attivi è basato sulla combinazione della chiralità di uno stereocentro con la chiralità planare del ferrocene disotituito un esempio del quale è il (-)-(R)-N,N-dimetil-1-[(S)-r,2-(difenilfosfino)-ferrocenil]etilammina [S.Sakuraba et al., Tetrahedron Asymmetry 1995, 6, 2503]. Among the diphosphines characterized by the presence of stereogenic phosphorus atoms, of the formula RR'R "P, the best known is (R, R) - DIPAMP [B.D.Vineyard et al.J.Am.Chem.Soc. 99.5946, (1977)]. Another type of optically active phosphine ligands is based on the combination of the chirality of a stereocenter with the planar chirality of the disubstituted ferrocene an example of which is (-) - (R) -N, N-dimethyl-1 - [(S) -r, 2- (diphenylphosphino) -ferrocenyl] ethylamine [S.Sakuraba et al., Tetrahedron Asymmetry 1995, 6, 2503].
Un ulteriore tipo di leganti otticamente attivi è basato su sistemi biarilici o bieteroarilici atropisomerici, nei quali la libera rotazione attraverso il legame semplice che connette i sistemi aromatici o eteroaromatici è bloccata da impedimenti sierici. Tra le difosfine biariliche a chiralità atropisomerica si devono citare il BINAP e il BIPHEMP i cui enantiomeri (S) hanno le strutture seguenti [R.Nojori et al. Acc.Chem.Res.23, 345 (1990), R.Schmid et al. Helv.Chim.Acta 71, 897, (1988)]: A further type of optically active ligands is based on atropisomeric biaryl or bieteroaryl systems, in which free rotation through the simple bond connecting the aromatic or heteroaromatic systems is blocked by serum impediments. Among the biaryl diphosphines with atropisomeric chirality we must mention BINAP and BIPHEMP whose (S) enantiomers have the following structures [R.Nojori et al. Acc. Chem. Res. 23, 345 (1990), R.Schmid et al. Helv.Chim.Acta 71, 897, (1988)]:
Tra le difosfine a chiralità atropisomerica basate sulla condensazione di sistemi bieteroramatici sono da citare il BITIOP e il BITIANP i cui enantiomeri R hanno le strutture seguenti [E. Cesarotti et al.WO 96/01831 del 25.01.1996]: Among the diphosphines with atropisomeric chirality based on the condensation of bieteroramatic systems we should mention BITIOP and BITIANP whose R-enantiomers have the following structures [E. Cesarotti et al. Wo 96/01831 of 25.01.1996]:
In tutti i leganti descritti la trasmissione dell’ informazione chirale localizzata sullo stereocentro o basata sullatropisomerismo viene trasmessa al substrato attraverso la disposizione assiale/equatoriale dei gruppi aromatici, in genere fenili, posti sull’atomo di fosforo; difosfine diverse da queste sono ad genere fenili, posti sull’atomo di fosforo; difosfine diverse da queste sono ad esempio il (R,R)-Et-DuPHOS [J. Feaster et al., Tetrahedron Lett. 46, 8321, 1996], mentre un legante a chiralità atropisomerica che ha dato risultati interessanti in una diversa reazione catalitica (idroformilazione delle olefine in presenza di idrogeno e ossido di carbonio) é il BINAPHOS [W.Leitner et al. Chem. Comm. 1999, 1663]: In all the ligands described, the transmission of chiral information localized on the stereocenter or based on atropisomerism is transmitted to the substrate through the axial / equatorial arrangement of the aromatic groups, generally phenyls, placed on the phosphorus atom; diphosphines other than these are of the phenyl genus, placed on the phosphorus atom; diphosphines other than these are for example (R, R) -Et-DuPHOS [J. Feaster et al., Tetrahedron Lett. 46, 8321, 1996], while a ligand with atropisomeric chirality that has given interesting results in a different catalytic reaction (hydroformylation of olefins in the presence of hydrogen and carbon monoxide) is BINAPHOS [W. Leitner et al. Chem. Comm. 1999, 1663]:
I leganti più recenti per catalizzatori di idrogenazione, al di là delle applicazioni pratiche, vengono provati in due reazioni tipiche: l’idrogenazione di N-acilammino acrilati a dare i corrispondenti animino acidi e la riduzione dei derivati dell’acido itaconico. Alcuni di questi catalizzatori sono altrettanto validi nella riduzione di gruppi carbonilici ed imminici; tra i leganti utilizzati risultati apprezzabili sono stati raggiunti utilizzando derivati di ammino alcoli come il (S)-PROLOPHOS, [E. Cesarotti et al.Tetrahedron Lett. 23, (1982) 2995] e il Ph-oxo-PRONOP [F.Agbossou et al. Coordination Chem.Rew. 178, (1998) 1615]. I gruppi imminici possono essere ridotti con grande stereoselettività utilizzando complessi di iridio con leganti imminofofinicifosfoniti come il seguente derivato della tert-eucina [R.Schmidt et al. Tetrahedron:Asymmetry, 1998, 9, 4043]: The most recent ligands for hydrogenation catalysts, beyond practical applications, are tested in two typical reactions: the hydrogenation of N-acylamino acrylates to give the corresponding amino acids and the reduction of itaconic acid derivatives. Some of these catalysts are equally valid in the reduction of carbonyl and imine groups; among the ligands used, appreciable results were achieved using derivatives of amino alcohols such as (S) -PROLOPHOS, [E. Cesarotti et al. Tetrahedron Lett. 23, (1982) 2995] and the Ph-oxo-PRONOP [F. Agbossou et al. Coordination Chem.Rew. 178, (1998) 1615]. Imino groups can be reduced with great stereoselectivity by using iridium complexes with iminophiniciphosphonite ligands such as the following derivative of tert-eucine [R.Schmidt et al. Tetrahedron: Asymmetry, 1998, 9, 4043]:
Di norma nella riduzione catalitica asimmetrica in fase omogenea il problema principale è rappresentato dalla sintesi della difosfina chirale. Negli esempi descritti in precedenza il processo di sintesi del legante fosfinico è piuttosto complesso, articolato su numerosi passaggi e con notevoli problemi di purificazione. Quando il legante non viene preparato a partire da sostanze otticamente attive tratte dal cosiddetto “chiral pool”, come i derivati degli amminoalcoli o i derivati dell’acido tartarico, la sintesi dei leganti difosfmici porta ad un racemo che deve essere risolto con un processo laborioso, in genere caratterizzato da basse rese e quindi da costi piuttosto elevati, che si traducono ovviamente in un aumento dei costi del catalizzatore e dell’intero processo di riduzione. As a rule, in the homogeneous phase asymmetric catalytic reduction the main problem is represented by the synthesis of chiral diphosphine. In the examples described above, the synthesis process of the phosphine ligand is rather complex, articulated on numerous steps and with considerable purification problems. When the binder is not prepared starting from optically active substances taken from the so-called "chiral pool", such as aminoalcohol derivatives or tartaric acid derivatives, the synthesis of the diphosphmic ligands leads to a raceme that must be resolved with a laborious process, generally characterized by low yields and therefore by rather high costs, which obviously translate into an increase in the costs of the catalyst and of the entire reduction process.
L’oggetto dell’invenzione The object of the invention
I leganti oggetto dell’ invenzione sono amminofosfiti chirali di formula Ia e Ib The ligands object of the invention are chiral aminophosphites of formula Ia and Ib
nelle quali in which
R, è idrogeno, arile, arile sostituito, alchile lineare o ramificato, cicloalchile; R, is hydrogen, aryl, substituted aryl, linear or branched alkyl, cycloalkyl;
R2 è alchile lineare o ramificato, arile, arile sostituito; oppure R2 is linear or branched alkyl, aryl, substituted aryl; or
R, e R2, presi assieme, formano una catena -(CH2)n-, con n = 3 o 4; R, and R2, taken together, form a chain - (CH2) n-, with n = 3 or 4;
R3 è idrogeno, arile, arile sostituito; R3 is hydrogen, aryl, substituted aryl;
P(Y)2 è un gruppo fosfito otticamente attivo a chiralità atropisomerica, derivato dall’ 1,1 ’-binaftolo, di formula IIa-IIb P (Y) 2 is an optically active phosphite group with atropisomeric chirality, derived from 1,1 '-binaphtol, of formula IIa-IIb
mentre -P(Y’)2 è un gruppo fosfito otticamente attivo a chiralità atropisomerica uguale a -P(Y)2 oppure un gruppo difosfino in cui Y’ può essere alchile, cicloalchile, arile, arile sostituito. while -P (Y ') 2 is an optically active phosphite group with atropisomeric chirality equal to -P (Y) 2 or a diphosphine group in which Y' can be alkyl, cycloalkyl, aryl, substituted aryl.
I leganti secondo l’invenzione consentono di ottenere catalizzatori chirali utilizzabili in reazioni stereocontrollate, dotati di alta chemo-, regio-, diasteroed enantioselettività e in grado di agire in condizioni di reazione molto blande (temperatura ambiente e pressione atmosferica o prossima a quella atmosferica) pur mantenendo elevate velocità di reazione e alta produttività. The ligands according to the invention allow to obtain chiral catalysts that can be used in stereocontrolled reactions, with high chemo-, regio-, diastero and enantioselectivity and able to act in very mild reaction conditions (ambient temperature and atmospheric pressure or close to atmospheric pressure) while maintaining high reaction rates and high productivity.
I sistemi catalitici chirali così ottenuti sono in grado di catalizzare la riduzione di substrati prochirali olefinici, carbonilici, enamminici ed imminici a dare alcoli, ammine e alcani con alti eccessi enantiomerici e diastereoisomerici. The chiral catalytic systems thus obtained are able to catalyze the reduction of olefinic, carbonyl, enamine and imine prochiral substrates to give alcohols, amines and alkanes with high enantiomeric and diastereoisomeric excesses.
Come risulta dalle formule Ia-Ib, gli amminofosfiti chirali oggetto dell’ invenzione sono costituiti da uno scheletro alifatico derivato da amminoalcoli recanti uno o più stereocentri, facilmente ottenibili dagli amminoacidi naturali, largamente disponibili a basso costo in entrambe le forme otticamente attive. Lo schema generale di sintesi è basato sull’attacco nucleofilo di un gruppo alcossi e/o di un gruppo amminico secondario su una clorofosfina o su un clorofosfinito chirale. Partendo da questo approccio sintetico è possibile preparare in un passaggio fosfiniti chelanti “simmetricamente” disostituiti con un gruppo chirale atropisomerico 1,1’-binaftilfosfito posizionato sull’atomo di ossigeno e sull’azoto secondario. In alternativa, è possibile preparare in due passaggi un amminofosfito “dissimmetricamente” sostituito nel quale l’atomo di ossigeno porta un gruppo dialchil- o diarilfosfino e l’azoto secondario un gruppo chirale atropisomerico 1,1’ -binaftilfosfito . As shown by the formulas Ia-Ib, the chiral aminophosphites object of the invention consist of an aliphatic skeleton derived from amino alcohols bearing one or more stereocenters, easily obtainable from natural amino acids, widely available at low cost in both optically active forms. The general synthesis scheme is based on the nucleophilic attack of an alkoxy group and / or a secondary amino group on a chlorophosphine or a chiral chlorophosphinite. Starting from this synthetic approach, it is possible to prepare "symmetrically" disubstituted chelating phosphinites in one step with an atropisomeric 1,1-binaphthylphosphite chiral group positioned on the oxygen atom and on the secondary nitrogen. Alternatively, it is possible to prepare in two steps a "dissymmetrically" substituted aminophosphite in which the oxygen atom carries a dialkyl- or diarylphosphine group and the secondary nitrogen a 1,1 '-binaphthylphosphite atropisomeric chiral group.
Il procedimento - che costituisce anch’esso un oggetto dell’invenzione -è illustrato nello schema n. 1 e può essere riassunto nei seguenti termini: The procedure - which is also an object of the invention - is illustrated in diagram no. 1 and can be summarized in the following terms:
- l’ammino alcol viene trattato con (R)-1,1’binaftilclorofosfito (4) (o con l’isomero (S)) in un solvente inerte, in presenza d’un accettore di HC1 (schema n. 1, reazione ii); 4 è ottenuto, secondo quanto riportato in letteratura, da 1,1’binaftolo otticamente puro; - the amino alcohol is treated with (R) -1,1'binaphthylchlorophosphite (4) (or with the isomer (S)) in an inert solvent, in the presence of a HC1 acceptor (scheme no. 1, reaction ii); 4 is obtained, as reported in the literature, from 1.1 optically pure binaphthol;
- filtrazione del cloridrato formatosi; - filtration of the hydrochloride formed;
- evaporazione del solvente a dare in forma chimicamente e otticamente pura l’ammino fosfito “simmetricamente” sostituito 6 (Ia, dove -P(Y’)2 = -P(Y)2). - evaporation of the solvent to give the "symmetrically" substituted amino phosphite 6 (Ia, where -P (Y ') 2 = -P (Y) 2) in chemically and optically pure form.
Alternativamente Alternatively
- l’ammino alcol 1 viene trattato con la quantità sostanzialmente stechiometrica di sodio idruro a dare l’alcolato 2. in THF, a temperatura stechiometrica di sodio idruro a dare l’alcolato 2 in THF, a temperatura ambiente e in condizioni rigorosamente anaerobiche e anidre (schema n. 1, reazione i) (la sostituzione del sodio idruro con litio butile, litio alluminio idruro, calcio idruro o sodio boroidruro porta a drastiche riduzioni della resa e alla formazione di miscele di prodotti difficilmente purificabili); - the amino alcohol 1 is treated with the substantially stoichiometric quantity of sodium hydride to give the alcoholate 2. in THF, at the stoichiometric temperature of sodium hydride to give the alcoholate 2 in THF, at room temperature and in strictly anaerobic conditions and anhydrous (scheme n. 1, reaction i) (the replacement of sodium hydride with lithium butyl, lithium aluminum hydride, calcium hydride or sodium borohydride leads to drastic reductions in yield and the formation of mixtures of products that are difficult to purify);
- l’alcolato 2, senza ulteriori purificazioni, viene trattato con la quantità sostanzialmente stechiometrica di una diclorofosfina a dare il fosfito 5 (schema n. 1, reazione iii); - alcohol 2, without further purification, is treated with the substantially stoichiometric amount of a dichlorophosphine to give phosphite 5 (scheme no. 1, reaction iii);
- si filtra il cloruro di sodio formatosi; - the sodium chloride formed is filtered;
- il filtrato viene trattato con (R)- o (S)-1,1’binaftilclorofosfito in presenza d’un accettore di HC1; - the filtrate is treated with (R) - or (S) -1,1 binaphthyl chlorophosphite in the presence of a HC1 acceptor;
- si filtra il cloridrato formatosi; - the formed hydrochloride is filtered;
- si evapora il solvente a dare in forma chimicamente e otticamente pura lamminofosfito “dissimmetricamente” sostituito 7 (la, dove Y’ = alchile, cicloalchile, arile o arile sostituito). - the solvent is evaporated to give in chemically and optically pure form "dissymmetrically" substituted laminophosphite 7 (la, where Y ’= alkyl, cycloalkyl, aryl or substituted aryl).
In qualità di solventi inerti si possono impiegare idrocarburi o eteri alifatici o aromatici, quali benzene, tolnene, esano, diisopropiletere, dietiletere, tetraidrofurano e simili; come accettori di HC1, basi terziarie quali trietilammina, piridina e simili. As inert solvents, aliphatic or aromatic hydrocarbons or ethers can be used, such as benzene, tolnene, hexane, diisopropylether, diethyl ether, tetrahydrofuran and the like; as HC1 acceptors, tertiary bases such as triethylamine, pyridine and the like.
Schema n. 1 Scheme n. 1
I leganti sono ottenuti in forma chimicamente pura come dimostrato attraverso la spettroscopia <31>P nmr, e possono essere utilizzati direttamente per la preparazione di complessi di metalli di transizione, in particolare metalli dell’VIII gruppo come Ru(II), Rh(I), Ir(I), Pd(II), Pt(II). Questi complessi - che costituiscono un ulteriore oggetto dell’ invenzione - vengono preparati per reazione di scambio tra lamminofosfito chirale e un complesso metallico recante un legante achirale legato al metallo più labilmente de ’amminofosfito (schema n. 2): The ligands are obtained in chemically pure form as demonstrated by <31> P nmr spectroscopy, and can be used directly for the preparation of transition metal complexes, in particular group VIII metals such as Ru (II), Rh (I ), Ir (I), Pd (II), Pt (II). These complexes - which constitute a further object of the invention - are prepared by exchange reaction between chiral laminophosphite and a metal complex bearing an achiral ligand bonded to the metal more loosely than aminophosphite (scheme no. 2):
Schema n. 2 Scheme n. 2
In genere il metallo reca come legante coordinato 1,5-cis,ciscicloottadiene (COD), etilene, benzonitrile, acetilacetone (Acac). Generally the metal has 1,5-cis coordinated ligand, ciscyclooctadiene (COD), ethylene, benzonitrile, acetylacetone (Acac).
La reazione di scambio procede rapidamente e quantitativamente in atmosfera inerte mescolando il complesso prescelto, sciolto in un solvente adatto, con il legante sciolto nello stesso solvente, in atmosfera inerte. La reazione viene seguita sia attraverso mutamenti cromatici, sia tramite le comuni tecniche spettroscopiche come 31P nmr e GC. I solventi utilizzati sono solventi clorurati, idrocarburi alifatici e aromatici, eteri, dimetilformammide. Al termine della reazione il solvente viene evaporato a secchezza e il complesso chirale formatosi viene utilizzato direttamente nelle reazioni catalitiche o purificato secondo le tecniche note. Questi catalizzatori vengono preferibilmente preparati al momento del loro impiego e utilizzati senza ulteriori purificazioni. The exchange reaction proceeds rapidly and quantitatively in an inert atmosphere, mixing the selected complex, dissolved in a suitable solvent, with the binder dissolved in the same solvent, in an inert atmosphere. The reaction is followed both through color changes and through common spectroscopic techniques such as 31P nmr and GC. The solvents used are chlorinated solvents, aliphatic and aromatic hydrocarbons, ethers, dimethylformamide. At the end of the reaction the solvent is evaporated to dryness and the chiral complex formed is used directly in the catalytic reactions or purified according to known techniques. These catalysts are preferably prepared at the time of their use and used without further purification.
Detti catalizzatori, costituiti da difosfina chirale e metallo di transizione, sono molto selettivi; infatti la geometria della difosfina legante definita dalla presenza di sistemi chirali rigidi di tipo atropisomerico, uniti alla profonda diversità elettronica degli atomi di fosforo, determina lunghezze ed angoli di legame diversi rispetto a quelli presenti nei leganti noti e tradizionali. Ne risultano un aumento della velocità di reazione, condizioni di reazione più blande quanto a temperatura, pressione parziale di idrogeno e concentrazione del catalizzatore o rapporto substrato/catalizzatore; infine, questi catalizzatori sono suscettibili di essere usati con solventi a minor impatto ambientale. Said catalysts, consisting of chiral diphosphine and transition metal, are very selective; in fact the geometry of the binder diphosphine defined by the presence of rigid chiral systems of the atropisomeric type, combined with the profound electronic diversity of the phosphorus atoms, determines different bond lengths and angles with respect to those present in known and traditional binders. The result is an increase in the reaction rate, milder reaction conditions in terms of temperature, partial pressure of hydrogen and concentration of the catalyst or substrate / catalyst ratio; finally, these catalysts are likely to be used with solvents with a lower environmental impact.
I catalizzatori sono caratterizzati da un’alta chemo-, enantio- e diastereoselettività e sono utilmente impiegati in reazioni catalitiche stereocontrollate, come la riduzione di olefine (-C=C-), di gruppi chetonici (>C=O), di gruppi imminici (-C=N-), di enammine (-N-C=C-), con ottenimento di composti otticamente attivi con elevati eccessi diastereoisomerici ed enantiomerici. The catalysts are characterized by a high chemo-, enantio- and diastereoselectivity and are usefully employed in stereocontrolled catalytic reactions, such as the reduction of olefins (-C = C-), ketone groups (> C = O), imine groups (-C = N-), of enamines (-N-C = C-), with obtaining optically active compounds with high diastereoisomeric and enantiomeric excesses.
Questi catalizzatori chirali vengono impiegati nella reazione di idroformilazione, nelle reazione di idrocianazione, nelle reazioni di isomerizzazione di doppi legami, nelle reazioni di formazione di legami C-C quali l’allilazione asimmetrica, il cross-coupling dei rettivi di grignard, nella reazione di Heck. These chiral catalysts are used in the hydroformylation reaction, in the hydrocyanation reaction, in the isomerization reactions of double bonds, in the reactions of formation of C-C bonds such as asymmetric allylation, the cross-coupling of grignard receptives, in the Heck reaction.
A titolo di esempio viene qui di seguito descritta la preparazione di alcuni amminofosfiti chirali, la preparazione di alcuni complessi chirali tra questi amminofosfiti e Rh, Pd e Pt nonché l’impiego di detti complessi come catalizzatori chirali nella riduzione dell’acido alfa-acetammidocinnamico, del suo metilestere, dell’itaconato di metile e nell’ idroformilazione dello stirene. By way of example, the preparation of some chiral aminophosphites, the preparation of some chiral complexes between these aminophosphites and Rh, Pd and Pt, as well as the use of said complexes as chiral catalysts in the reduction of alpha-acetamidocinamic acid, is described below, of its methyl ester, of methyl itaconate and in the hydroformylation of styrene.
ESEMPIO 1 EXAMPLE 1
Preparazione del’amminofosfito “7-(Ambu)-RR” (Ia. dove R, = R2 = Et; R3 = H; Y’ = C6H5). Preparation of the aminophosphite "7- (Ambu) -RR" (Ia. Where R, = R2 = Et; R3 = H; Y '= C6H5).
a) Sintesi di (R)-O-Difenilfosfio-(2-N-etil)amminobutanolo-1,5R. a) Synthesis of (R) -O-Diphenylphosphio- (2-N-ethyl) aminobutanol-1,5R.
In una provetta munita di rubinetto laterale, in atmosfera inerte di argon, si pongono 125.4 mgr di NaH (PM=24;mmol=5.22) sospeso in 10 ml di THF distillato in condizioni anaerobiche. Si aggiungono goccia a goccia tramite siringa, attraverso un setto di gomma, 604.1 mgr di 2-(R)-N-etilamminobutanolo-1 1R (dove R1 = R2 = Et; R3 = H) (PM=1 17.1; mmol=5.16) e la sospensione viene lasciata sotto agitazione per 30 minuti; la sospensione viene raffreddata a 0°C e alla medesima si aggiungono, goccia a goccia tramite siringa, sempre agitando 1.137 gr di difenilclorofosfina (PM=220.64; mmol=5.16). Dopo l’aggiunta si lascia in agitazione per circa un’ora lasciando che la sospensione ritorni lentamente a temperatura ambiente. 125.4 mgr of NaH (MW = 24; mmol = 5.22) suspended in 10 ml of THF distilled under anaerobic conditions are placed in a test tube fitted with a side tap, in an inert argon atmosphere. 604.1 mgr of 2- (R) -N-ethylaminobutanol-1 1R (where R1 = R2 = Et; R3 = H) (PM = 1 17.1; mmol = 5.16 are added drop by drop by syringe through a rubber septum ) and the suspension is left under stirring for 30 minutes; the suspension is cooled to 0 ° C and added drop by drop using a syringe, still stirring 1.137 g of diphenylchlorophosphine (MW = 220.64; mmol = 5.16). After the addition, it is left to stir for about an hour, letting the suspension slowly return to room temperature.
Per favorire la precipitazione del NaCl si aggiungono 10 mi di etere isopropilico distillato in atmosfera inerte. Si filtra la soluzione con rigorosa esclusione dell’aria e si concentra a pressione ridotta ottenendo 915.6 mg di 5R sotto forma di un solido biancastro e colloso che viene utilizzato nel passaggio successivo senza ulteriori purificazioni. To favor the precipitation of NaCl, 10 ml of isopropyl ether distilled in an inert atmosphere are added. The solution is filtered with strict air exclusion and concentrated under reduced pressure obtaining 915.6 mg of 5R in the form of a whitish and sticky solid which is used in the next step without further purification.
<31>P-NMR (300 MHz) (C6D6) (ppm): 114.5 (s, -0-P(Ph)2); spettrometria di massa (i.e.): (M<+>) 302. <31> P-NMR (300 MHz) (C6D6) (ppm): 114.5 (s, -0-P (Ph) 2); mass spectrometry (i.e.): (M <+>) 302.
b) Sintesi di (R)-1,1-binaftil-2,2’-difosfito, 4R b) Synthesis of (R) -1,1-binaphthyl-2,2'-diphosphite, 4R
Una sospensione di (R)-1,1 ’-bi-2 -naftolo (422.4 mgr; PM=286; 1.47mmol) e 1-metil-2-pirrolidone (0.001 gr; 0.01 mmol) in PC13 (3.025 gr; PM=137.2; 22.05 mmol) viene scaldata a 75°C in bagno termostatato per il tempo strettamente necessario alla completa solubilizzazione della sospensione (5 minuti al massimo: un riscaldamento prolungato infatti comporta la formazione di sottoprodotti e un drastico abbassamento delle rese). Si procede poi alla rimozione, a pressione ridotta, del PCI3 in eccesso. Per eliminarne ogni traccia si solubilizza il composto in 10 mi di toluene che viene evaporato a pressione ridotta. Questa operazione va ripetuta per tre volte. Si ottengono così 437.8 mg di un composto vetroso e colloso; il composto viene quantitativamente trasformato in un solido pulverulento bianco per agitazione con 10 ml di esano distillato e degasato in atmosfera inerte. A suspension of (R) -1,1 '-bi-2 -naphthol (422.4 mgr; PM = 286; 1.47mmol) and 1-methyl-2-pyrrolidone (0.001 gr; 0.01 mmol) in PC13 (3.025 gr; PM = 137.2; 22.05 mmol) is heated to 75 ° C in a thermostated bath for the time strictly necessary for the complete solubilization of the suspension (maximum 5 minutes: in fact, prolonged heating involves the formation of by-products and a drastic reduction in yields). The excess PCI3 is then removed under reduced pressure. To eliminate all traces, the compound is solubilized in 10 ml of toluene which is evaporated under reduced pressure. This operation must be repeated three times. 437.8 mg of a glassy and sticky compound are thus obtained; the compound is quantitatively transformed into a white powdery solid by stirring with 10 ml of distilled hexane and degassed in an inert atmosphere.
<31>P-NMR (300 MHz) (C6D6) (ppm): 179.2 ; spettrometria di massa (i.e.): (M<+>) 350. <31> P-NMR (300 MHz) (C6D6) (ppm): 179.2; mass spectrometry (i.e.): (M <+>) 350.
Resa(calcolata all’NMR con l’ausilio di trifenilfosfinossido come standard interno): 437.8 mgr di 4R(C20H12O2PCl: PM=350.4);resa%: 85% c) Sintesi di “7-(Ambu)RR”. In una provetta munita di rubinetto laterale, sotto N2, si pongono 510 mgr di 5R, (PM=301.34; mmol=1.7), preparato come descritto al punto a), sciolto in 10 mi di toluene distillato e degasato. Si aggiungono 0.42 mi di trietilammina (PM=101.19; mmol= 2.55; d=0.73) e si porta la soluzione a 0°C. Si aggiungono lentamente 594.5 mgr di 4R (PM=350.4; mmol= 2.95), preparato di fresco come descritto al punto b), sciolti in 10 ml di toluene in atmosfera inerte. Yield (calculated at NMR with the aid of triphenylphosphine oxide as an internal standard): 437.8 mgr of 4R (C20H12O2PCl: PM = 350.4); yield%: 85% c) Synthesis of "7- (Ambu) RR". 510 mgr of 5R, (MW = 301.34; mmol = 1.7), prepared as described in point a), dissolved in 10 ml of distilled and degassed toluene, are placed in a test tube equipped with a side tap, under N2. 0.42 ml of triethylamine (MW = 101.19; mmol = 2.55; d = 0.73) are added and the solution is brought to 0 ° C. 594.5 mgr of 4R (MW = 350.4; mmol = 2.95), freshly prepared as described in point b), are slowly added, dissolved in 10 ml of toluene in an inert atmosphere.
Si agita la soluzione per 16 ore lasciandola risalire lentamente a temperatura ambiente. Per facilitare la precipitazione del cloruro di trietilammonio si aggiungono 10 ml di etere isopropilico distillato e degasato. Si filtra sotto N2 e si concentra a pressione ridotta. Si ottiene un solido bianco giallastro colloso che, per trattamento con 10 mi di esano distillato e degasato, in atmosfera inerte e sotto agitazione, si trasforma in un precipitato bianco polverulento di 7-(Ambul-RR. Si ottengono 670 mg di prodotto The solution is stirred for 16 hours, allowing it to rise slowly to room temperature. To facilitate the precipitation of the triethylammonium chloride, 10 ml of distilled and degassed isopropyl ether are added. It filters under N2 and concentrates under reduced pressure. A sticky yellowish white solid is obtained which, by treatment with 10 ml of distilled and degassed hexane, in an inert atmosphere and under stirring, is transformed into a white powdery precipitate of 7- (Ambul-RR. 670 mg of product are obtained.
<3I>P-NMR (300 MHz) (C6D6) (ppm): 151.3 (s, N-P(0)2), 115.5 (s, O-P(Ph)2); spettrometria di massa (i.e.): (M<+>) 615; [α]<20>D = -212.9 (c = 0.070, C6H6). <3I> P-NMR (300 MHz) (C6D6) (ppm): 151.3 (s, N-P (0) 2), 115.5 (s, O-P (Ph) 2); mass spectrometry (i.e.): (M <+>) 615; [α] <20> D = -212.9 (c = 0.070, C6H6).
ESEMPIO 2 EXAMPLE 2
Preparazione dell'amminofosfito “7-(Ambu)-RS”. Preparation of the aminophosphite “7- (Ambu) -RS”.
a) Sintesi di (R)-O-Difenilfosfino-(2-N-etil)amminobutanolo-1 5R. La preparazione è analoga a quella riportata al punto a) dell’Esempio 1. a) Synthesis of (R) -O-Diphenylphosphino- (2-N-ethyl) aminobutanol-1 5R. The preparation is similar to that reported in point a) of Example 1.
b) Sintesi di (S)-1,1-binaftil-2,2’-difosfito 4S. La preparazione è analoga a quella riportata al punto b) dell’Esempio 1, utilizzando come prodotto di partenza il (S)-1,1’-Bi-2-naftolo. b) Synthesis of (S) -1,1-binaphthyl-2,2'-diphosphite 4S. The preparation is similar to that reported in point b) of Example 1, using (S) -1,1-Bi-2-naphthol as the starting product.
c) Sintesi di “7-(Ambu)-RS”. La preparazione è analoga a quella riportata al punto c) dell’Esempio 1. Si ottengono 650 mg di prodotto c) Summary of “7- (Ambu) -RS”. The preparation is similar to that reported in point c) of Example 1. 650 mg of product are obtained
ESEMPIO 3 EXAMPLE 3
Preparazione dellamminofosfito “ Preparation of aminophosphite "
a) Sintesi di (R)-1,1 ’-binaftil-2,2’-difosfito 4R. Si veda il punto b) dell’Esempio 1. a) Synthesis of (R) -1,1 '-binaphthyl-2,2'-diphosphite 4R. See point b) of Example 1.
b) Sintesi di b) Summary of
In un provetta munita di rubinetto laterale, sotto N2, si pone una soluzione ottenuta sciogliendo 76.6 mgr di (S)-(+)2-pirrolidinmetanolo 1S (dove (PM=101.15; mmol=0.76) in 10 mi di toluene distillato e degasato; si aggiungono 0.32 mi di trietilammina e si raffredda la soluzione a 0°C. Lentamente, sotto agitazione, si aggiungono 532.6 mgr di 4R preparato di fresco come riportato al punto a) Si lascia in agitazione per tutta la notte facendo risalire lentamente la temperatura a temperatura ambiente. Si aggiungono 10 mi di etere isopropilico distillato e degasato per favorire la precipitazione del cloruro di trietilammonio formatosi. Si filtra in atmosfera inerte e si concentra a pressione ridotta. Si ottiene un solido bianco-giallastro vetroso e colloso che, per trattamento con 10 ml di esano distillato e degasato, in atmosfera inerte e sotto agitazione energica, si trasforma in un solido pulverulento giallo paglierino. Si ottengono 470.9 mg di prodotto. A solution obtained by dissolving 76.6 mgr of (S) - (+) 2-pyrrolidinmethanol 1S (where (MW = 101.15; mmol = 0.76) in 10 ml of distilled and degassed toluene is placed in a test tube equipped with a side tap, under N2 ; 0.32 ml of triethylamine are added and the solution is cooled to 0 ° C. Slowly, under stirring, 532.6 mgr of 4R freshly prepared as reported in point a) are added. at room temperature. 10 ml of distilled and degassed isopropyl ether are added to favor the precipitation of the triethylammonium chloride formed. It is filtered in an inert atmosphere and concentrated under reduced pressure. A glassy and sticky white-yellowish solid is obtained which, by treatment with 10 ml of distilled and degassed hexane, in an inert atmosphere and under vigorous stirring, turns into a pale yellow powdery solid. 470.9 mg of product are obtained.
ESEMPIO 4 EXAMPLE 4
Preparazione dellamminofosfito . Preparation of aminophosphite.
a) Sintesi di (S)-1,1-binaftil-2,2’-difosfito 4S . La preparazione è analoga a quella riportata al punto b) dell’Esempio 1, utilizzando come prodotto di partenza il (S)-1,1'-bi-2-naftolo. a) Synthesis of (S) -1,1-binaphthyl-2,2'-diphosphite 4S. The preparation is similar to that reported in point b) of Example 1, using (S) -1,1'-bi-2-naphthol as starting product.
b) Sintesi di La preparazione è analoga a quella riportata al punto b) dell’Esempio 3. Si ottengono 450 mg di prodotto. b) Summary of The preparation is similar to that reported in point b) of Example 3. 450 mg of product are obtained.
ESEMPIO 5 EXAMPLE 5
Preparazione del complesso Preparation of the complex
In un provetta con rubinetto laterale codato sotto azoto si pongono 18 mgr di R sciolti in 4 mi di cloruro di metilene distillato e degasato; si aggiungono 10.5 mgr di preparato secondo le note tecniche di laboratorio, sciolto a sua volta in 2 ml di cloruro di metilene distillato e degasato. La soluzione vira rapidamente dal rosso all’arancione intenso; si lascia reagire per circa mezz’ora, quindi si evapora il solvente a pressione ridotta. Si ottiene un solido rosso-mattone che viene utilizzato come catalizzatore di idrogenazione senza ulteriore purificazione. Si ottengono 24.4 mgr di prodotto. 18 mgr of R dissolved in 4 ml of distilled and degassed methylene chloride are placed in a test tube with side tap coded under nitrogen; 10.5 mgr of preparation according to known laboratory techniques are added, dissolved in turn in 2 ml of distilled and degassed methylene chloride. The solution quickly turns from red to intense orange; it is left to react for about half an hour, then the solvent is evaporated at reduced pressure. A brick-red solid is obtained which is used as a hydrogenation catalyst without further purification. 24.4 mgr of product are obtained.
ESEMPIO 6 EXAMPLE 6
Preparazione del complesso Preparation of the complex
La preparazione è analoga a quella riportata nell’Esempio 5, utilizzando lamminofosfito ”. Si ottengono 21.3 mg di prodotto. The preparation is similar to that reported in Example 5, using laminophosphite ". 21.3 mg of product are obtained.
ESEMPIO 7 EXAMPLE 7
Preparazione del complesso Preparation of the complex
In una provetta si pongono 27.3 mgr di preparato secondo le tecniche note, sciolti per riscaldamento in 3 ml di etanolo. 27.3 mgr of preparation according to known techniques are placed in a test tube, dissolved by heating in 3 ml of ethanol.
Si aggiungono 51 mgr di sciolti in 3 mi di cloruro di metilene sotto N2. La soluzione viene lasciata sotto agitazione a temperatura ambiente per 90 minuti; successivamente il volume della soluzione viene ridotto del 50% per evaporazione. La soluzione risultante viene trattata con 10ml di esano. Si forma immediatamente un precipitato giallo paglierino che viene filtrato e lavato con porzioni successive di esano (5 mi) fino a quando non si elimina l’odore tipico del benzonitrile. Si ottengono 44,9 mg di prodotto. 51 mgr of dissolved in 3 ml of methylene chloride under N2 are added. The solution is left under stirring at room temperature for 90 minutes; subsequently the volume of the solution is reduced by 50% by evaporation. The resulting solution is treated with 10ml of hexane. A straw yellow precipitate is immediately formed which is filtered and washed with successive portions of hexane (5 ml) until the typical odor of benzonitrile is eliminated. 44.9 mg of product are obtained.
ESEMPIO 8 EXAMPLE 8
Preparazione del complesso Preparation of the complex
In una provetta si pongono 23.5 mgr di PtCl2(COD), preparato secondo le tecniche note, sciolti in 3 ml di cloruro di metilene. Sotto agitazione si aggiungono 36.92 mgr di sciolti in 3 ml di cloruro di metilene. Si lascia la soluzione sotto agitazione per 30 minuti e si elimina il cloruro di metilene a pressione ridotta, fino a ottenere un precipitato biancoverde. Il solido viene reso pulverulento e filtrabile per agitazione della sospensione ottenuta aggiungendo al solido 10 ml di etere etilico e agitando per un’ora. Si decanta la sospensione e il solido rimasto viene evaporato a secchezza. Si ottengono 43.6 mg di prodotto. In a test tube are placed 23.5 mgr of PtCl2 (COD), prepared according to known techniques, dissolved in 3 ml of methylene chloride. While stirring, 36.92 mgr of dissolved in 3 ml of methylene chloride are added. The solution is left under stirring for 30 minutes and the methylene chloride is removed under reduced pressure, until a white-green precipitate is obtained. The solid is made powdery and filterable by stirring the suspension obtained by adding 10 ml of ethyl ether to the solid and stirring for one hour. The suspension is decanted and the remaining solid is evaporated to dryness. 43.6 mg of product are obtained.
ESEMPIO 9 EXAMPLE 9
Riduzione di acido alfa-acetammidocinnamico. Reduction of alpha-acetamidocinnamic acid.
Un’autoclave di vetro da 100 mi, munita di agitazione magnetica, viene più volte pressurizzata a 3 atm. con idrogeno ed evacuata (il ciclo viene ripetuto almeno 5 volte) e termostata a 30°C. Al catalizzatore preparato secondo l’Esempio 5 si aggiungono 486 mg di di acido alfaacetammidocinnamico sciolti in 20 ml di THF, preventivamente distillato da Na/benzofenone. La soluzione viene trasferita nell’autoclave per mezzo di una siringa e l’autoclave viene pressurizzata ad 1.2 atm. Il decorso della reazione viene seguito attraverso la caduta di pressione del manometro e attraverso prelievi dall’autoclave ad intervalli regolari di 1 ora; tramite l NMR è possibile seguire la progressiva scomparsa del singoletto del gruppo acetile a 2.1 ppm e la concomitante comparsa del gruppo metilico della N-Acetilfenilalanina a 1.9 ppm. A conversione completa (6 ore) la soluzione viene trattata con resina DOWEX 50 per rimuovere il catalizzatore, filtrata e portata a secchezza. Il residuo viene sciolto in metanolo e analizzato polarimetricamente: [a]<25>D = - 27.6. A 100 ml glass autoclave, equipped with magnetic stirring, is pressurized several times to 3 atm. with hydrogen and evacuated (the cycle is repeated at least 5 times) and thermostated at 30 ° C. To the catalyst prepared according to Example 5, 486 mg of alphaacetamidocinnamic acid dissolved in 20 ml of THF, previously distilled from Na / benzophenone, are added. The solution is transferred into the autoclave by means of a syringe and the autoclave is pressurized to 1.2 atm. The course of the reaction is followed through the pressure drop of the pressure gauge and through withdrawals from the autoclave at regular intervals of 1 hour; through NMR it is possible to follow the progressive disappearance of the singlet of the acetyl group at 2.1 ppm and the concomitant appearance of the methyl group of N-Acetylphenylalanine at 1.9 ppm. After complete conversion (6 hours) the solution is treated with DOWEX 50 resin to remove the catalyst, filtered and brought to dryness. The residue is dissolved in methanol and polarimetrically analyzed: [a] <25> D = - 27.6.
ESEMPIO 10 EXAMPLE 10
Riduzione di acido alfa-acetammidocinnamico metilestere. Reduction of alpha-acetamide methyl ester.
Un’autoclave di acciaio da 100 ml, munita di agitazione magnetica, viene più volte pressurizzata a 100 atm. con idrogeno ed evacuata (il ciclo viene ripetuto almeno 5 volte) e termostata a 0°C. Al catalizzatore preparato secondo l’Esempio 5 si aggiungono 517.1 mg di di acido alfaacetammidocinnamico metilestere sciolti in 20 mi di THF, preventivamente distillato da Na/benzofenone. La soluzione viene trasferita nell’autoclave per mezzo di una siringa e l’autoclave viene pressurizzata ad 100 atm. Il decorso della reazione viene seguito prelievi dall’autoclave ad intervalli regolari di 15 minuti ; tramite Ή NMR è possibile seguire la progressiva scomparsa del singoletto del gruppo acetile a 2.1 ppm e la concomitante comparsa del gruppo metilico della N-Acetilfenilalanina a 1.9 ppm. A conversione completa, dopo 1 ora, l’autoclave viene ventilata e la soluzione viene trattata con resina DOWEX 50 per rimuovere il catalizzatore, filtrata e portata a secchezza. Il residuo viene sciolto esano/isopropanolo 9/1 e analizzato usando una HPLC con colonna chirale CHIRALCEL OD®: eccesso enantiomerico del 60% in favore dell’enantiomero (R)-(-). A 100 ml steel autoclave, equipped with magnetic stirring, is pressurized several times to 100 atm. with hydrogen and evacuated (the cycle is repeated at least 5 times) and thermostated at 0 ° C. To the catalyst prepared according to Example 5, 517.1 mg of alphaacetamidocinnamic acid methyl ester dissolved in 20 ml of THF, previously distilled from Na / benzophenone, are added. The solution is transferred into the autoclave by means of a syringe and the autoclave is pressurized to 100 atm. The course of the reaction is followed by withdrawals from the autoclave at regular intervals of 15 minutes; through Ή NMR it is possible to follow the progressive disappearance of the singlet of the acetyl group at 2.1 ppm and the concomitant appearance of the methyl group of N-Acetylphenylalanine at 1.9 ppm. After complete conversion, after 1 hour, the autoclave is ventilated and the solution is treated with DOWEX 50 resin to remove the catalyst, filtered and brought to dryness. The residue is dissolved in hexane / isopropanol 9/1 and analyzed using an HPLC with CHIRALCEL OD® chiral column: enantiomeric excess of 60% in favor of the (R) - (-) enantiomer.
ESEMPIO 11 EXAMPLE 11
Riduzione di acido alfa-acetammidocinnamico. Reduction of alpha-acetamidocinnamic acid.
Si opera come descritto nell’Esempio 9, utilizzando il catalizzatore descritto nell’Esempio 6. Dopo cinque ore la conversione è completa; la misura polarimetrica fornisce un [α]<25>D = 13.0. We operate as described in Example 9, using the catalyst described in Example 6. After five hours the conversion is complete; the polarimetric measurement gives a [α] <25> D = 13.0.
ESEMPIO 12 EXAMPLE 12
Riduzione di acido alfa-acetammidocinnamico metilestere. Reduction of alpha-acetamide methyl ester.
Si opera come descritto nell’Esempio 10, utilizzando il catalizzatore descritto nell’esempio 6. L’autoclave è stata termostatata a 30°C. La conversione risulta completa dopo 0.05 ore (3 minuti). L’eccesso enantiomerico è risultato del 44% in favore dell’enantiomero (S)-(+). We operate as described in Example 10, using the catalyst described in Example 6. The autoclave was thermostated at 30 ° C. The conversion is complete after 0.05 hours (3 minutes). The enantiomeric excess was 44% in favor of the (S) - (+) enantiomer.
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT2001MI001322A ITMI20011322A1 (en) | 2001-06-22 | 2001-06-22 | MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT2001MI001322A ITMI20011322A1 (en) | 2001-06-22 | 2001-06-22 | MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES |
Publications (2)
Publication Number | Publication Date |
---|---|
ITMI20011322A0 ITMI20011322A0 (en) | 2001-06-22 |
ITMI20011322A1 true ITMI20011322A1 (en) | 2002-12-22 |
Family
ID=11447921
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IT2001MI001322A ITMI20011322A1 (en) | 2001-06-22 | 2001-06-22 | MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES |
Country Status (1)
Country | Link |
---|---|
IT (1) | ITMI20011322A1 (en) |
-
2001
- 2001-06-22 IT IT2001MI001322A patent/ITMI20011322A1/en unknown
Also Published As
Publication number | Publication date |
---|---|
ITMI20011322A0 (en) | 2001-06-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6037500A (en) | Asymmetric synthesis catalyzed by transition metal complexes with cyclic chiral phosphine ligands | |
Selke | Carbohydrate phosphinites as chiral ligands for asymmetric synthesis catalyzed by complexes: V. New rhodium (I)-chelates prepared by precipitation from the equilibrium between neutral and cationic complexes and hydrolysis of their bonded ligands | |
WO1997047633A9 (en) | Asymmetric synthesis catalyzed by transition metal complexes with cyclic chiral phosphine ligands | |
CA2559242A1 (en) | Cycloolefin phosphine ligands and their use in catalysis | |
Chen et al. | Asymmetric activation of conformationally flexible monodentate phosphites for enantioselective hydrogenation | |
JP2006502843A (en) | Chiral transition metal catalyst and catalytic production method of chiral organic compound using the catalyst | |
Akotsi et al. | Versatile precursor to ruthenium‐bis (phosphine) hydrogenation catalysts | |
US6337406B1 (en) | Asymmetric catalysis based on chiral phospholanes and hydroxyl phospholanes | |
JP2011503221A (en) | Bidentate chiral ligands used in catalytic asymmetric addition reactions | |
Moritz et al. | P-Chirogenic Diphosphazanes with Axially Chiral Substituents and Their Use in Rh-Catalyzed Asymmetric Hydrogenation | |
EP1299401B1 (en) | Chiral ligands for asymmetric catalysis | |
US6207868B1 (en) | Asymmetric synthesis catalyzed by transition metal complexes with chiral ligands | |
US6613922B2 (en) | Phosphorus p-cyclophane ligands and their use in transition metal catalyzed asymmetric reactions | |
US20040176618A1 (en) | Asymmetric catalysis based on chiral phospholanes and hydroxyl phospholanes | |
EP1200452A1 (en) | Novel chiral phosphorus ligands and the use thereof in the production of optically active products | |
CA2594893C (en) | Metallocene-based chiral phosphines and arsines | |
JP2003535834A (en) | Chiral monophosphites as ligands for asymmetric synthesis | |
US20090227805A1 (en) | Axially Asymmetric Phosphorus Compound and Production Method Thereof | |
ITMI20011322A1 (en) | MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES | |
Naili et al. | New chiral aminophosphine carboxyphosphinite ligands (AMPCP). Synthesis and application in asymmetric hydrogenation and hydroformylation | |
EP1030854B1 (en) | Catalysts for asymmetric synthesis containing rigid chiral ligands | |
CN114085251B (en) | Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof | |
JP5009613B2 (en) | Chiral ligands for use in asymmetric synthesis | |
WO2006082054A1 (en) | 1,4-bis-diphosphines, 1,4-bis-diphosphites and 1,4-bis- diphosphonites from optically active (z)-olefines as chiral ligands | |
Junge et al. | Synthesis and catalytic application of novel binaphthyl-derived phosphorous ligands |