NO773738L - PROCEDURES FOR ASYMMETRIC HYDROGENATION - Google Patents
PROCEDURES FOR ASYMMETRIC HYDROGENATIONInfo
- Publication number
- NO773738L NO773738L NO773738A NO773738A NO773738L NO 773738 L NO773738 L NO 773738L NO 773738 A NO773738 A NO 773738A NO 773738 A NO773738 A NO 773738A NO 773738 L NO773738 L NO 773738L
- Authority
- NO
- Norway
- Prior art keywords
- bis
- rhodium
- alpha
- benzene
- ethylenediamine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 18
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 title claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 230000003197 catalytic effect Effects 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 239000010948 rhodium Substances 0.000 claims description 7
- 229910052703 rhodium Inorganic materials 0.000 claims description 6
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 150000001336 alkenes Chemical class 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- WJIBZZVTNMAURL-UHFFFAOYSA-N phosphane;rhodium Chemical compound P.[Rh] WJIBZZVTNMAURL-UHFFFAOYSA-N 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 229940012017 ethylenediamine Drugs 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XQJHRCVXRAJIDY-UHFFFAOYSA-N aminophosphine Chemical class PN XQJHRCVXRAJIDY-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000004913 cyclooctene Substances 0.000 description 2
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 2
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- -1 lithium aluminum hydride Chemical compound 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- IKGHIFGXPVLPFD-LLVKDONJSA-N methyl (2r)-2-acetamido-3-phenylpropanoate Chemical compound COC(=O)[C@H](NC(C)=O)CC1=CC=CC=C1 IKGHIFGXPVLPFD-LLVKDONJSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 150000003284 rhodium compounds Chemical class 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
- VFUFIIXSVCSRBQ-LLVKDONJSA-N (2R)-2-acetamido-3-(3-acetyloxy-4-methoxyphenyl)propanoic acid Chemical compound C(C)(=O)OC=1C=C(C[C@@H](NC(C)=O)C(=O)O)C=CC1OC VFUFIIXSVCSRBQ-LLVKDONJSA-N 0.000 description 1
- XNCRUNXWPDJHGV-BQYQJAHWSA-N (e)-2-methyl-3-phenylprop-2-enoic acid Chemical compound OC(=O)C(/C)=C/C1=CC=CC=C1 XNCRUNXWPDJHGV-BQYQJAHWSA-N 0.000 description 1
- JMSUNAQVHOHLMX-UHFFFAOYSA-N 1-cyclohexylethanol Chemical compound CC(O)C1CCCCC1 JMSUNAQVHOHLMX-UHFFFAOYSA-N 0.000 description 1
- RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
- JNWXFQFXLMWGRL-UHFFFAOYSA-N 2-acetamido-3-(3-acetyloxy-4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(C=C(NC(C)=O)C(O)=O)C=C1OC(C)=O JNWXFQFXLMWGRL-UHFFFAOYSA-N 0.000 description 1
- UFDFFEMHDKXMBG-UHFFFAOYSA-N 2-acetamidoprop-2-enoic acid Chemical compound CC(=O)NC(=C)C(O)=O UFDFFEMHDKXMBG-UHFFFAOYSA-N 0.000 description 1
- WXUAQHNMJWJLTG-UHFFFAOYSA-N 2-methylbutanedioic acid Chemical compound OC(=O)C(C)CC(O)=O WXUAQHNMJWJLTG-UHFFFAOYSA-N 0.000 description 1
- MSIFHGPIEOZWQZ-UHFFFAOYSA-N 3-chlorobicyclo[2.2.1]hepta-1,3-diene;rhodium Chemical compound [Rh].C1CC2=CC(Cl)=C1C2 MSIFHGPIEOZWQZ-UHFFFAOYSA-N 0.000 description 1
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 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
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical compound OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- KTHDTJVBEPMMGL-GSVOUGTGSA-N n-acetylalanine Chemical compound OC(=O)[C@@H](C)NC(C)=O KTHDTJVBEPMMGL-GSVOUGTGSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—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
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/46—Phosphinous acids [R2POH], [R2P(= O)H]: Thiophosphinous acids including[R2PSH]; [R2P(=S)H]; Aminophosphines [R2PNH2]; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
- C07F9/4883—Amides or esteramides thereof, e.g. RP(NR'2)2 or RP(XR')(NR''2) (X = O, S)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Fremgangsmåte for katalytisk asymmetrisk hydrogenering. Process for catalytic asymmetric hydrogenation.
Foreliggende oppfinnelse vedrører en fremgangsmåte for katalytisk asymmetrisk hydrogenering av organiske forbindelser valgt fra prochirale olefiner og forbindelser med C0-og eller CN-grupper, og det særegne ved fremgangsmåten i henhold til oppfinnelsen er det som katalysatorsystem anvendes et rhodiumkompleks med formel The present invention relates to a method for the catalytic asymmetric hydrogenation of organic compounds selected from prochiral olefins and compounds with C0 and or CN groups, and the distinctive feature of the method according to the invention is that a rhodium complex with the formula is used as a catalyst system
hvori in which
L står for enten L stands for either
N,N"-bis-[S(-)alfa-metylbenzyl]-N,N'-bis-(difenyl-fosfin)-etylendiamin, eller N,N"-bis-[S(-)alpha-methylbenzyl]-N,N'-bis-(diphenyl-phosphine)-ethylenediamine, or
N,N'-bis-[R(+)alfa-metylbenzyl]-N,N'-bis-(difenyl-fosfin)-etylendiamin, og N,N'-bis-[R(+)alpha-methylbenzyl]-N,N'-bis-(diphenyl-phosphine)-ethylenediamine, and
S står for 1 mol benzen,S stands for 1 mole of benzene,
idet rhodium-fosfin-komplekset er erholdt fra omsetning i benzen mellom en forbindelse L og en rhodiumholdig kooridi-nasjonsforbindelse valgt fra the rhodium-phosphine complex being obtained from reaction in benzene between a compound L and a rhodium-containing coordination compound selected from
u-diklortetrakis-etylen-dirhodium (I), u-dichlorotetrakis-ethylene-dirhodium (I),
la-diklortetrakis-cyklookten-dirhodium (I) og la-dichlorotetrakis-cyclooctene-dirhodium (I) and
u-diklor-bis- (norbornadien) -dirhodium (I)u-dichloro-bis-(norbornadiene)-dirhodium (I)
idet hydrogeneringen gjennomføres med molforhold substrat/- katalysator på fra 10.000 til 10, ved reaksjonstemperatur mellom -70 og +200°C og under hydrogentrykk i området 1 - 100 bar. the hydrogenation being carried out with a substrate/catalyst molar ratio of from 10,000 to 10, at a reaction temperature between -70 and +200°C and under hydrogen pressure in the range 1 - 100 bar.
Disse trekk ved oppfinnelsen fremgår av patentkravet. These features of the invention appear in the patent claim.
Fremstilling av optisk aktive organiske forbindelser med høy optisk renhet på industriell basis, som f. eks venstre-dreiende aminosyrer, er fremdeles nesten utelukkende avhengig av prosesser av biokjemisk eller mikrobiologisk type. Production of optically active organic compounds with high optical purity on an industrial basis, such as, for example, left-handed amino acids, is still almost exclusively dependent on processes of a biochemical or microbiological type.
Inntil for noen år siden kjente man ikke til noen forsøk av ren kjemisk type som på grunn av prosessøkonomi og optisk utbytte var i stand til å konkurrere med de ovennevnte Until a few years ago, no experiments of a purely chemical type were known which, due to process economy and optical yield, were able to compete with the above-mentioned
biologiske metoder.biological methods.
Oppdagelsen av nye homogene katalytiske systemer med høy stereospesifikk virkning, som f. eks tris-(trifenyl-fosfin)-klor-rhodium, og nye fremskritt i syntese av asymmetriske fosforbaserte forfiner førte til fremstilling av chirale komplekser av rhodium med høy stereoselektivitet ved hydrogenering av prochirale olefiner. The discovery of new homogeneous catalytic systems with high stereospecific activity, such as e.g. tris-(triphenyl-phosphine)-chloro-rhodium, and new advances in the synthesis of asymmetric phosphorus-based morphines led to the preparation of chiral complexes of rhodium with high stereoselectivity by hydrogenation of prochiral olefins.
Følgende asymmetriske aminofosfiner L ble funnet brukbare som ligand i det kompleksdannede katalysatorsystem som anvendes ved den asymmetriske hydrogeneringsfremgangsmåte i henhold til oppfinnelsen: N,N'-bis-[S(-)a-metylbenzyl]-N,N'-bis-(difenylfosfin)-etylen-diamin, og The following asymmetric aminophosphines L were found usable as ligands in the complexed catalyst system used in the asymmetric hydrogenation method according to the invention: N,N'-bis-[S(-)a-methylbenzyl]-N,N'-bis-(diphenylphosphine) )-ethylenediamine, and
N,N'-bis-[R(+)a-metylbenzyl]-N,N'-bis-(difenylfosfin)-etylen-diamin. N,N'-bis-[R(+)α-methylbenzyl]-N,N'-bis-(diphenylphosphine)-ethylenediamine.
Fremstillingen av de angjeldende asymmetriske aminofosfiner gjennomføres ved å gå ut fra forbindelser som inneholder ett eller flere ikke-racemiske chiralsentere. Den nevnte fremstilling av forbindelsene kan ellers gjennomføres i henhold til tidligere kjente prosesser for fremstilling av tilsvarende achirale forbindelser. The production of the asymmetric aminophosphines in question is carried out starting from compounds containing one or more non-racemic chiral centers. The aforementioned production of the compounds can otherwise be carried out according to previously known processes for the production of corresponding achiral compounds.
Det aktive katalytiske kompleks som anvendes ved fremgangsmåten i henhold til oppfinnelsen dannes ved å omsette en eller begge de nevnte asymmetriske aminofosfin-forbindelser (eller ligander) med en koordiansjonsforbindelse av rhodium, og følgende rhodiumoforbindelser ble funnet brukbare, nemlig The active catalytic complex used in the method according to the invention is formed by reacting one or both of the aforementioned asymmetric aminophosphine compounds (or ligands) with a coordination compound of rhodium, and the following rhodium compounds were found useful, namely
u-diklortetrakis-etylen-dirhodium (I) u-dichlorotetrakis-ethylene-dirhodium (I)
u-diklortetrakis-cyklookten-dirhodium (I) og u-diklor-bis-(norbornadien)-dirhodium (I). u-dichlorotetrakis-cyclooctene-dirhodium (I) and u-dichloro-bis-(norbornadiene)-dirhodium (I).
Som reaksjonsløsningsmiddel for fremstillingen av rhodium- As a reaction solvent for the production of rhodium-
komplekset ble det anvendt benzen.the complex, benzene was used.
Reaksjonen med asymmetrisk hydrogenering gjennomføres ved et molforhold mellom substrat og katalysator varierende mellom 10.000 og 10. Reaksjonstemperaturen kan være mellom -70°C og +200°C, foretrukket mellom 0 og 50°C. Hydrogentrykket er i området 1 til 100 atmosfærer. The reaction with asymmetric hydrogenation is carried out at a molar ratio between substrate and catalyst varying between 10,000 and 10. The reaction temperature can be between -70°C and +200°C, preferably between 0 and 50°C. The hydrogen pressure is in the range 1 to 100 atmospheres.
De følgende eksempler illustrerer oppfinnelsen.The following examples illustrate the invention.
Eksempel 1Example 1
N,N'-bis-[(S(-)alfametylbenzyl]-etylendiamin fremstilles ved å gå ut fra S(-)alfametylbenzylamin og dietyl-oksalat. Reduksjonen av diaminet gjennomføres med litiumaluminium-hydrid i THF og det tilsvarende diamin isoleres som dihydrokloridet med smeltepunkt 250°C (utbytte: 80 %). N,N'-bis-[(S(-)alphamethylbenzyl]-ethylenediamine is prepared starting from S(-)alphamethylbenzylamine and diethyl oxalate. The reduction of the diamine is carried out with lithium aluminum hydride in THF and the corresponding diamine is isolated as the dihydrochloride with melting point 250°C (yield: 80%).
Etter at dihydrokloridet er blitt klaret med 10 % NaOH, behandles 0,050 mol av diaminet med 0,100 mol difenylkloro-fosfin i 300 ml vannfri benzen, i nærvær av 0,200 mol trietylamin. After the dihydrochloride has been clarified with 10% NaOH, 0.050 mole of the diamine is treated with 0.100 mole of diphenylchlorophosphine in 300 ml of anhydrous benzene, in the presence of 0.200 mole of triethylamine.
Blandingen kokes under tilbakeløp i 20 timer, hydrokloridet av trietylammonium frafiltreres og benzenløsningen kon-sentreres inntil N,N'-[bis-(S(-)alfametylbenzyl]-N,N'-bis-(difenylfosfin)-etylendiamin separeres, smeltepunkt 138 - 140°C (utbytte 70 % i forhold til utgangs-diaminet). The mixture is refluxed for 20 hours, the triethylammonium hydrochloride is filtered off and the benzene solution is concentrated until N,N'-[bis-(S(-)alphamethylbenzyl]-N,N'-bis-(diphenylphosphine)-ethylenediamine is separated, melting point 138 - 140°C (yield 70% in relation to the starting diamine).
Katalysatoren fremstilles ved å behandle 5,5 mg rhodium (I) u-diklortetrakis-(etylen) (17,7 • 10~<6>mol) med 22,5 mg N,N'-bis-(S(-)alfametylbenzyl)-N,N'-(difenylfosfin)-etylendiamin 835,4 • 10~<6>mol), idet 6 ml vannfri benzen anvendes som reaksj ons-løsningsmiddel. The catalyst is prepared by treating 5.5 mg of rhodium (I) u-dichlorotetrakis-(ethylene) (17.7 • 10~<6>mol) with 22.5 mg of N,N'-bis-(S(-)alphamethylbenzyl )-N,N'-(diphenylphosphine)-ethylenediamine 835.4 • 10~<6>mol), with 6 ml of anhydrous benzene being used as reaction solvent.
Atomforhold P/Rh = 2Atomic ratio P/Rh = 2
Oppløsningen overføres i en kolbe inneholdende 2,8 g alfaacetamido-kanelsyre i 24 ml vannfri metanol, idet kolben forbindes til et hydrogeneringsapparat som arbeider ved atmosfæretrykk og som er termostatinnstilt til 25°C, og hvormed det gjennomføres en omhyggelig spyling av reaksjons-omgivelsene med hydrogen før det katalytiske kompleks tilsettes. The solution is transferred into a flask containing 2.8 g of alpha-acetamido-cinnamic acid in 24 ml of anhydrous methanol, the flask being connected to a hydrogenation apparatus that works at atmospheric pressure and which is thermostatically set to 25°C, and with which a careful flushing of the reaction surroundings with hydrogen before the catalytic complex is added.
Reaksjonsforløpet styres ved vanlig måleteknikk.The course of the reaction is controlled by standard measuring techniques.
Den initiale hastighet for hydrogenabsorpsjon er omtrentThe initial rate of hydrogen absorption is approx
4 ml/min, målt under arbeidsbetingelsene.4 ml/min, measured under working conditions.
Etter 3 timer er omdannelsen omtrent 85 %. Reaksjonen avsluttes og reaksjonsproduktet separeres ved avdamping av løsningsmidlet under reduserte trykk. After 3 hours, the conversion is approximately 85%. The reaction is terminated and the reaction product is separated by evaporating the solvent under reduced pressure.
Restproduktet behandles med en 0,5 N NaOH-løsning og den uoppløselige katalysator frafiltreres. The residual product is treated with a 0.5 N NaOH solution and the insoluble catalyst is filtered off.
Den vandige løsning gjøres sur til pH 2 - 3 med fortynnet HC1, og den organiske fase ekstraheres fem ganger med etyleter. De kombinerte eterfraksjoner tørkes over Na2S04. Eteren avdampes så. Restproduktet, undersøkt ved spektroskopi (NMR, IR) består av R(-)N-acetylfenyl-alanin-[a]§° = -40 The aqueous solution is acidified to pH 2 - 3 with dilute HCl, and the organic phase is extracted five times with ethyl ether. The combined ether fractions are dried over Na 2 SO 4 . The ether is then evaporated. The residual product, examined by spectroscopy (NMR, IR) consists of R(-)N-acetylphenyl-alanine-[a]§° = -40
(c = 1, EtOH 95 %) med et optisk utbytte på 84 %. Den spesifikke rotasjon for enantiomert rent S(+)N-acetylfenyl-alanin er [a]2° = +47,5(c = 1, EtOH 95 %). (c = 1, EtOH 95%) with an optical yield of 84%. The specific rotation for enantiomerically pure S(+)N-acetylphenyl-alanine is [a]2° = +47.5(c = 1, EtOH 95%).
Eksempel 2Example 2
Ved å gjenta fremgangsmåten beskrevet i eksempel 1 og ved å anvende R(+) alfa-metylbenzylaminet, med to chiralitets-sentere med motsatte konfigurasjon i forhold til de tilsvarende i difosfinet i eksempel 1. By repeating the procedure described in example 1 and by using the R(+) alpha-methylbenzylamine, with two chirality centers with the opposite configuration in relation to the corresponding ones in the diphosphine in example 1.
Liganden omsettes med den samme rhodiumforbindelse som i Eks. The ligand is reacted with the same rhodium compound as in Ex.
1 og det katalytiske system anvendes ved hydrogenering av alfa-acetamido-kanelsyre. Det hydrogenerte produkt, etter isolering og undersøkelse som i eksempel 1, består av S(+)N-acetylfenyl-alanin, med en iakttatt rotsjon [a]§^ = +38,9 1 and the catalytic system is used in the hydrogenation of alpha-acetamido-cinnamic acid. The hydrogenated product, after isolation and examination as in example 1, consists of S(+)N-acetylphenyl-alanine, with an observed rotation [a]§^ = +38.9
(c = 1, EtOH 95 %) indikerende en enantiomerisk renhet på(c = 1, EtOH 95%) indicating an enantiomeric purity of
82 %. 82%.
Eksempel 3Example 3
Det katalytiske kompleks fremstilt i henhold til fremgangsmåten i eksempel 1, ved å gå ut fra 47,9 mg rhodium (I) u-dikloro-tetrakiscyklookten (66,8 • 10<->^ mol) og 86 mg N,N'-(S(-)metylbenzyl)-N,N'-(difenylfosfin)-etylen-diamin (135 • 10~<6>mol) anvendes ved den katalytiske hydrogenering av 3-acetoksy-4-metoksy-alfaacetamido-kanelsyre (2 g) under atmosfæretrykk ved 25°C. Ved å arbeide som beskrevet i eksempel 1, isoleres 3-acetoksy-4-metoksy-N-acetyl-(R)-fenylalanin fra reaksjonsblandingen med et utbytte på The catalytic complex prepared according to the procedure in example 1, starting from 47.9 mg of rhodium (I) u-dichloro-tetrakiscyclooctene (66.8 • 10<->^ mol) and 86 mg of N,N'- (S(-)methylbenzyl)-N,N'-(diphenylphosphine)-ethylenediamine (135 • 10~<6>mol) is used in the catalytic hydrogenation of 3-acetoxy-4-methoxy-alphaacetamido-cinnamic acid (2 g ) under atmospheric pressure at 25°C. By working as described in Example 1, 3-acetoxy-4-methoxy-N-acetyl-(R)-phenylalanine is isolated from the reaction mixture with a yield of
85 - 90 %, [a]<g2>-16,9 (c = 1, aceton).85-90%, [α]<g2>-16.9 (c = 1, acetone).
Det optiske utbytte er 77 %, og det enantiomere rene 3-acetoksy-4-metoksy-n-acetyl-(R)-fenyl-alanin har [a]§<2>= -22 (c = 1, aceton). The optical yield is 77%, and the enantiomerically pure 3-acetoxy-4-methoxy-n-acetyl-(R)-phenyl-alanine has [a]§<2>= -22 (c = 1, acetone).
Eksempel 4Example 4
Det katalytiske kompleks fremstilt i henhold til eksempel 1, ved å gå ut fra rhodium (I) u-diklortetrakis-(etylen) The catalytic complex prepared according to example 1, starting from rhodium (I) u-dichlorotetrakis-(ethylene)
(73 • 10~<6>mol) og N,N'-(S(-)alfa-metylbenzyl)-N,N<*->(difenyl-fosfin)-etylen-diamin (146 • 10<->^ mol) anvendes ved katalytisk hydrogenering av 3,4-metylendioksyd-alfa-acetamido-kanelsyre (6,98 • IO<-6>mol) ved 25° og under atmosfæretrykk. (73 • 10~<6>mol) and N,N'-(S(-)alpha-methylbenzyl)-N,N<*->(diphenyl-phosphine)-ethylene-diamine (146 • 10<->^ mol) is used in the catalytic hydrogenation of 3,4-methylenedioxide-alpha-acetamido-cinnamic acid (6.98 • 10<-6>mol) at 25° and under atmospheric pressure.
Ved å utarbeide som beskrevet i eksempel 1, isoleres 3,4-metylen-dioksy-N-acetyl-(R)-fenyl-alanin med kvantitativt utbytte, [a]J<8>= -53,4 (c = 1,8, EtOH 95 %) By preparing as described in Example 1, 3,4-methylene-dioxy-N-acetyl-(R)-phenyl-alanine is isolated in quantitative yield, [a]J<8>= -53.4 (c = 1, 8, EtOH 95%)
Optisk utbytte: 7 5 %.Optical yield: 75%.
Det enantiomere rene 3,4-metylendioksy-N-acetyl-(R)-fenyl- The enantiomerically pure 3,4-methylenedioxy-N-acetyl-(R)-phenyl-
alanin har [ct]£<8>= -53,4 (c = 1,8 EtOH 95 %)alanine has [ct]£<8>= -53.4 (c = 1.8 EtOH 95%)
Eksempel 5Example 5
Det katalytiske kompleks fremstilt i henhold til fremgangsmåten i eksempel 1, ved å gå ut fra rhodium (I) u-dikloro-tetrakis-(cyklookten) (13,9 • IO"<6>mol) og N.N'-(S(-)alfa-metylbenzyl) -N,N'-(difenyl-fosfin)-etylendiamin (27,5 • IO-<6>mol) anvendes ved den katalytiske hydrogenering ved 25°C og under atmosfæretrykk av alfa-acetamido-akrylsyre (15,5 • 10~<3>mol). Det N-acetyl-(R)-alanin som isoleres med kvantitativt utbytte har [a]§<5>= 48,5. Optisk utbytte: 73 %. The catalytic complex prepared according to the procedure in example 1, starting from rhodium (I) u-dichloro-tetrakis-(cyclooctene) (13.9 • 10"<6>mol) and N.N'-(S (-)alpha-methylbenzyl)-N,N'-(diphenyl-phosphine)-ethylenediamine (27.5 • 10-<6>mol) is used in the catalytic hydrogenation at 25°C and under atmospheric pressure of alpha-acetamido-acrylic acid (15.5 • 10~<3>mol). The N-acetyl-(R)-alanine which is isolated in quantitative yield has [a]§<5>= 48.5. Optical yield: 73%.
Eksempel 6Example 6
Det katalytiske kompleks fremstilt som beskrevet i eksempel 1, ved å gå ut fra rhodium (I) u-diklortetrakis-(cyklookten) The catalytic complex prepared as described in example 1, starting from rhodium (I) u-dichlorotetrakis-(cyclooctene)
(146 • 10~<6>mol) og N,N'-(S(-)alfa-metylbenzyl)-N,N'-(difenyl-fosfin)-etylendiamin (278 • IO<-6>mol), anvendes ved den katalytiske hydrogenering av metylesteren av alfa-acetamido-kanelsyre (13,7 • IO<-3>mol). (R)-N-acetylfenyl-alaninmetylesteren, som isoleres ved kromatografering på silikagel, har [a]§<5>= -10 (c = 1,9 MeOH). (146 • 10~<6>mol) and N,N'-(S(-)alpha-methylbenzyl)-N,N'-(diphenyl-phosphine)-ethylenediamine (278 • 10<-6>mol), are used by the catalytic hydrogenation of the methyl ester of alpha-acetamido-cinnamic acid (13.7 • IO<-3>mol). The (R)-N-acetylphenylalanine methyl ester, which is isolated by chromatography on silica gel, has [a]§<5>= -10 (c = 1.9 MeOH).
Optisk utbytte: 46,5 %Optical yield: 46.5%
Den enantiomere rene S(-)N-acetylfenyl-alaninmetylester har [a]§<5>= +21,4 (c = 1,9 MeOH). The enantiomerically pure S(-)N-acetylphenyl-alanine methyl ester has [a]§<5>= +21.4 (c = 1.9 MeOH).
Eksempel 7Example 7
Det katalytiske kompleks som fremstilt i henhold til fremgangsmåten beskrevet i eksempel 1, ved å gå ut fra rhodium (I) u-diklortetrakis-(etylen) (77 • IO-<6>mol) og N,N'-(S(-)alfa-metylbenzyl)-N,N1 -(difenylfosfin-etylendiamin) The catalytic complex as prepared according to the method described in example 1, starting from rhodium (I) u-dichlorotetrakis-(ethylene) (77 • IO-<6>mol) and N,N'-(S(- )alpha-methylbenzyl)-N,N1 -(diphenylphosphine-ethylenediamine)
(154 • IO-<6>mol), anvendes ved den katalytiske hydrogenering av propen-2,3-dikarboksylsyre (15 • IO<-3>) ved 15,5 atmosfærer og 30°C. (154 • IO-<6>mol), is used in the catalytic hydrogenation of propene-2,3-dicarboxylic acid (15 • IO<-3>) at 15.5 atmospheres and 30°C.
Propan-2,3-dikarboksylsyren-(R), isolert med kvantitativt utbytte, har [a]§<5>= -1,5 (c = 1, H20). Optisk utbytte: 10 %. The propane-2,3-dicarboxylic acid-(R), isolated in quantitative yield, has [a]§<5>= -1.5 (c = 1, H2O). Optical yield: 10%.
Eksempel 8Example 8
Det katalytiske kompleks som fremstilt i henhold til fremgangsmåten beskrevet i eksempel 1, ved å gå ut fra rhodium (I) u-diklorotetrakis-(etylen) (72 • IO-<6>mol) og N,N'-S(-)-alfa-metylbenzyl-N,N'-(difenylfosfin)-etylendiamin (146 • IO<-6>mol) anvendes ved den katalytiske hydrogenering av alfa-metylkanelsyre ved 5 atmosfærer og 25°C. 2-benzyl-propionsyren-(S) kvantitativt gjenvunnet i henhold til fremgangsmåten beskrevet i eksempel 1, har [a]§^ = -1 (c = 1, benzen) The catalytic complex as prepared according to the method described in example 1, starting from rhodium (I) u-dichlorotetrakis-(ethylene) (72 • IO-<6>mol) and N,N'-S(-) -alpha-methylbenzyl-N,N'-(diphenylphosphine)-ethylenediamine (146 • 10<-6>mol) is used in the catalytic hydrogenation of alpha-methylcinnamic acid at 5 atmospheres and 25°C. The 2-benzyl-propionic acid-(S) quantitatively recovered according to the method described in Example 1, has [a]§^ = -1 (c = 1, benzene)
Optisk utbytte: 4 %Optical yield: 4%
Eksempel 9Example 9
7 ml vannfri metanol og 5 g acetofenon innføres i en autoklav under nitrogenatmosfære. En løsning av 2 ml benzen inneholdende 18,7 mg rhodiumkloro-norbornadien [RhClNBD]2dimer og 56,3 mg N,N'-bis-(S(-)alfa-metylbenzyl)-N,N'-(difenyl-fosfin)-etylendiamin (PNNP) tilsettes så. Etter et det er opprettet vakuumbetingelser fylles autoklaven med H2ved tykk 12 atmosfærer. Etter 12 timer ved romtemperatur var 4 atmosfærer hydrogen absorbert med en omdannelse på omtrent 80 %. reaksjonen avbrytes på dette tidspunkt. Benzen og metanol fjernes under redusert trykk og deretter gjenvinnes ved fraksjonert vakuumdestillasjon 3,9 g av et produkt som etter spektroskopisk analyse (NMR), består av R(+)l-metyl-fenyl-karbinol [a]§° = -7,4 rent produkt). Optisk renhet: 17 % ([a]8° = +44,2). 7 ml of anhydrous methanol and 5 g of acetophenone are introduced into an autoclave under a nitrogen atmosphere. A solution of 2 ml of benzene containing 18.7 mg of rhodium chloro-norbornadiene [RhClNBD]2dimer and 56.3 mg of N,N'-bis-(S(-)alpha-methylbenzyl)-N,N'-(diphenyl-phosphine) -ethylenediamine (PNNP) is then added. After vacuum conditions have been created, the autoclave is filled with H2 at a thickness of 12 atmospheres. After 12 hours at room temperature, 4 atmospheres of hydrogen had been absorbed with a conversion of approximately 80%. the reaction is stopped at this point. Benzene and methanol are removed under reduced pressure and then recovered by fractional vacuum distillation 3.9 g of a product which, according to spectroscopic analysis (NMR), consists of R(+)l-methyl-phenyl-carbinol [a]§° = -7, 4 pure product). Optical purity: 17% ([a]8° = +44.2).
Eksempel 10Example 10
Katalysatoren fremstilles fra 45 mg [RhClNBD]2og 124 mg (PNNP) i 3 mol benzen. En slik katalytisk løsning innføres i en autoklav inneholdende 5 g cykloheksyl-metylketon i 7 ml metanol. Autoklaven bringes til 12 atmosfærer trykk med hydrogen. Etter 48 timer ved romtemperatur var omtrent 3 atmosfærer H2absorbert. Reaksjonen avbrytes. Med en fremgangsmåte tilsvarende den i eksempel 1 ble det gjenvunnet 3,15 g av et produkt som er R(-)1-cykloheksyl-etanol The catalyst is prepared from 45 mg [RhClNBD]2 and 124 mg (PNNP) in 3 mol benzene. Such a catalytic solution is introduced into an autoclave containing 5 g of cyclohexyl methyl ketone in 7 ml of methanol. The autoclave is brought to 12 atmospheres pressure with hydrogen. After 48 hours at room temperature, about 3 atmospheres of H2 had been absorbed. The reaction is interrupted. With a method similar to that in example 1, 3.15 g of a product which is R(-)1-cyclohexyl ethanol was recovered
[a]2° = -0,430 (ren forbindelse) med optisk utbytte 8 %. [a]2° = -0.430 (pure compound) with optical yield 8%.
( [a]g° = -5,5) .([a]g° = -5.5) .
Eksempel 11Example 11
En kolbe inneholdende 2 ml benzen tilføres 24,2 mg [RhClNBD]2og 66,8 mg (PNNP), deretter tilsettes 2,28 ml difenylsilan. Kolben kjøles ved 0°C og 1,21 g acetofenon-anil. A flask containing 2 ml of benzene is charged with 24.2 mg of [RhClNBD]2 and 66.8 mg of (PNNP), then 2.28 ml of diphenylsilane is added. The flask is cooled at 0°C and 1.21 g of acetophenone-anil.
(hvori 0 står for fenyl) i 6 ml benzen tilsettes dråpevis. Etter 12 timer, fremdeles ved 0°C, tilsettes 4 ml 10 % HC1 og aceton inntil det oppnås en homogen løsning, etter filtrering av hydrolyseproduktene. Etter fjernelse av aceton under redusert trykk tilsettes 100 ml 5 % HC1 og blandingen ekstraheres 6 ganger med 25 ml Et20. Den vandige fase gjøres alkalisk med 2 N NaOH og dne nye organiske fase, oppnådd ved ekstrahering fire ganger med 20 ml Et20, tørkes over Na2SC>4. Deretter fjernes eteren. Restproduktet destilleres under vakuum og til slutt oppnås 7 00 mg av en forbindelse identi-fisert som R(-)N-fenyl-N-metyl-benzylamin med [a]j)2^ = -3,29 (c = 2,15, EtOH). Optisk renhet: 12,2 %. ([a]fj° = 26,1). (where 0 stands for phenyl) in 6 ml of benzene is added dropwise. After 12 hours, still at 0°C, 4 ml of 10% HCl and acetone are added until a homogeneous solution is obtained, after filtering the hydrolysis products. After removal of acetone under reduced pressure, 100 ml of 5% HCl are added and the mixture is extracted 6 times with 25 ml of Et 2 O. The aqueous phase is made alkaline with 2 N NaOH and the new organic phase, obtained by extraction four times with 20 ml of Et2O, is dried over Na2SO4. The ether is then removed. The residual product is distilled under vacuum and finally 700 mg of a compound identified as R(-)N-phenyl-N-methyl-benzylamine with [a]j)2^ = -3.29 (c = 2.15 , EtOH). Optical purity: 12.2%. ([a]fj° = 26.1).
Eksempel 12Example 12
Ved å gå frem som beskrevet i eksempel 11 og ved å anvende en katalytisk løsning omfattende 19 mg [RhClNBD]2og 55 mg (PNNP) i 2 ml benzen omsettes 4,3 g etylpyruvat i 10 ml benzen med 5,79 g difenylsilan i 5 ml benzen. I dette eksempel, til forskjell fra eksempel 11, tilsettes silanet dråpevis til løsningen av de andre reaksjonskomponenter holdt ved 0°C. Etter to timer, fremdeles ved 0°C, gjennomføres hydrolysen ved hjelp av 30 ml MeOH inneholdende 10 mg p-toluensulfonsyre. Etter filtrering og fjernelse av metanol isoleres 3,5 g D(+)etyl-laktat, [a]§° = 3,25 ved fraksjonert destillasjon. Optisk renhet: 22,4% ([a]<2>,<0>=14,5. By proceeding as described in example 11 and by using a catalytic solution comprising 19 mg of [RhClNBD]2 and 55 mg of (PNNP) in 2 ml of benzene, 4.3 g of ethyl pyruvate in 10 ml of benzene is reacted with 5.79 g of diphenylsilane in 5 ml of benzene. In this example, in contrast to example 11, the silane is added dropwise to the solution of the other reaction components kept at 0°C. After two hours, still at 0°C, the hydrolysis is carried out using 30 ml of MeOH containing 10 mg of p-toluenesulfonic acid. After filtration and removal of methanol, 3.5 g of D(+)ethyl lactate, [a]§° = 3.25, is isolated by fractional distillation. Optical purity: 22.4% ([a]<2>,<0>=14.5.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2265376A IT1063212B (en) | 1976-04-26 | 1976-04-26 | Asymmetric hydrogenation of olefins, carbonyl cpds. or nitriles - using transition metal complex of asymmetric amino-phosphine |
| IT2013977A IT1113753B (en) | 1977-02-10 | 1977-02-10 | Asymmetric hydrogenation of olefins, carbonyl cpds. or nitriles - using transition metal complex of asymmetric amino-phosphine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO773738L true NO773738L (en) | 1977-10-27 |
Family
ID=26327413
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO771419A NO771419L (en) | 1976-04-26 | 1977-04-25 | NEW AMINOPHOSPHINES AND PROCEDURES FOR THEIR PREPARATION |
| NO773738A NO773738L (en) | 1976-04-26 | 1977-10-31 | PROCEDURES FOR ASYMMETRIC HYDROGENATION |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO771419A NO771419L (en) | 1976-04-26 | 1977-04-25 | NEW AMINOPHOSPHINES AND PROCEDURES FOR THEIR PREPARATION |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS52151127A (en) |
| AU (2) | AU523259B2 (en) |
| CA (1) | CA1109074A (en) |
| CH (1) | CH629166A5 (en) |
| DD (2) | DD137233A5 (en) |
| DE (3) | DE2718533C3 (en) |
| DK (1) | DK180877A (en) |
| FR (1) | FR2349555A1 (en) |
| GB (1) | GB1580461A (en) |
| HU (2) | HUT33991A (en) |
| LU (1) | LU77197A1 (en) |
| NL (1) | NL180096C (en) |
| NO (2) | NO771419L (en) |
| SE (2) | SE434918B (en) |
| YU (1) | YU107577A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1087963B (en) * | 1977-10-17 | 1985-06-04 | Snam Progetti | ASYMMETRICAL HYDROGENATION OF PROCHIRAL OLEFINS BY COMPLEX OF TRANSITION METALS IMMOBILIZED IN CLAY MINERALS. |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2116905A5 (en) * | 1970-12-10 | 1972-07-21 | Inst Francais Du Petrole | NEW BIDENT COORDINATES, THEIR MANUFACTURING AND THEIR APPLICATIONS |
-
1977
- 1977-04-06 CA CA275,775A patent/CA1109074A/en not_active Expired
- 1977-04-19 AU AU24407/77A patent/AU523259B2/en not_active Ceased
- 1977-04-21 GB GB16691/77A patent/GB1580461A/en not_active Expired
- 1977-04-22 DD DD77206208A patent/DD137233A5/en unknown
- 1977-04-22 CH CH503677A patent/CH629166A5/en not_active IP Right Cessation
- 1977-04-22 DD DD7700198557A patent/DD132487A5/en unknown
- 1977-04-25 NO NO771419A patent/NO771419L/en unknown
- 1977-04-25 DK DK180877A patent/DK180877A/en not_active Application Discontinuation
- 1977-04-25 HU HU82465A patent/HUT33991A/en unknown
- 1977-04-25 LU LU77197A patent/LU77197A1/xx unknown
- 1977-04-25 HU HU82466A patent/HUT34037A/en unknown
- 1977-04-25 FR FR7712435A patent/FR2349555A1/en active Granted
- 1977-04-25 YU YU01075/77A patent/YU107577A/en unknown
- 1977-04-25 SE SE7704738A patent/SE434918B/en not_active IP Right Cessation
- 1977-04-26 DE DE2718533A patent/DE2718533C3/en not_active Expired
- 1977-04-26 JP JP4750177A patent/JPS52151127A/en active Granted
- 1977-04-26 DE DE2759683A patent/DE2759683C3/en not_active Expired
- 1977-04-26 DE DE2759684A patent/DE2759684C2/en not_active Expired
- 1977-04-26 NL NLAANVRAGE7704570,A patent/NL180096C/en not_active IP Right Cessation
- 1977-10-31 NO NO773738A patent/NO773738L/en unknown
-
1983
- 1983-09-09 SE SE8304837A patent/SE460066B/en not_active IP Right Cessation
-
1984
- 1984-07-12 AU AU30546/84A patent/AU572169B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CH629166A5 (en) | 1982-04-15 |
| DE2718533C3 (en) | 1980-08-28 |
| DE2759683B1 (en) | 1980-07-17 |
| JPS633871B2 (en) | 1988-01-26 |
| SE460066B (en) | 1989-09-04 |
| SE434918B (en) | 1984-08-27 |
| NL180096B (en) | 1986-08-01 |
| JPS52151127A (en) | 1977-12-15 |
| DE2718533A1 (en) | 1977-11-24 |
| SE7704738L (en) | 1977-10-27 |
| AU572169B2 (en) | 1988-05-05 |
| DD137233A5 (en) | 1979-08-22 |
| LU77197A1 (en) | 1977-08-17 |
| FR2349555A1 (en) | 1977-11-25 |
| DE2759684C2 (en) | 1986-05-28 |
| HUT34037A (en) | 1985-01-28 |
| NO771419L (en) | 1977-10-27 |
| FR2349555B1 (en) | 1980-12-26 |
| SE8304837L (en) | 1983-09-09 |
| DK180877A (en) | 1977-10-27 |
| AU3054684A (en) | 1984-12-20 |
| NL180096C (en) | 1987-01-02 |
| CA1109074A (en) | 1981-09-15 |
| DE2718533B2 (en) | 1979-12-20 |
| GB1580461A (en) | 1980-12-03 |
| DE2759683C3 (en) | 1981-10-15 |
| DD132487A5 (en) | 1978-10-04 |
| HUT33991A (en) | 1985-01-28 |
| SE8304837D0 (en) | 1983-09-09 |
| YU107577A (en) | 1983-02-28 |
| NL7704570A (en) | 1977-10-28 |
| AU523259B2 (en) | 1982-07-22 |
| AU2440777A (en) | 1979-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0135392B1 (en) | Rhodium-phosphine complexes | |
| DE69635874T2 (en) | Process for the preparation of optically active alcohols | |
| Burk et al. | New chiral phospholanes; synthesis, characterization, and use in asymmetric hydrogenation reactions | |
| SU615852A3 (en) | Method of obtaining optically-active amino acids | |
| Wink et al. | Practical syntheses of chelating bis (dioxaphospholane) ligands through chlorodioxaphospholane intermediates and demonstration of catalytic competence of bis (phosphite) rhodium cation | |
| EP0036741B1 (en) | Phosphine compounds, transition metal complexes thereof and use thereof as chiral hydrogenation catalysts | |
| JP7130624B2 (en) | Stable hydroformylation catalysts for the preparation of high N/ISO ratio aldehyde products | |
| US4604474A (en) | Rhodium-phosphine complex | |
| US7589218B2 (en) | Chiral spiro compounds and their use in asymmetric catalytic reactions | |
| Ewalds et al. | Application of P‐stereogenic aminophosphine phosphinite ligands in asymmetric hydroformylation | |
| Herranz et al. | Osmium-catalyzed vicinal oxyamination of olefins by N-chloro-N-metallocarbamates | |
| US11708316B2 (en) | Hydrogenation of esters to alcohols in the presence of a Ru-PNN complex | |
| Townsend et al. | Novel copper complexes of chiral diphosphines: preparation, structure, and use to form rhodium complex catalysts for chiral hydrogenations | |
| Fordyce et al. | Hydrido (phosphine) ruthenate complexes and their role in the catalytic hydrogenation of arenes | |
| NO773738L (en) | PROCEDURES FOR ASYMMETRIC HYDROGENATION | |
| CN111848673A (en) | Cyclohexyl fused ring spiroindane diphosphine ligand | |
| JPH04159288A (en) | Optically active phosphine compound | |
| JP2000136193A (en) | Optically acitive bisphosphinomethane and assymetric synthesis using its phodium or copper complex | |
| CN109251227B (en) | Chiral compound containing ferrocene skeleton and rigid spiro structure, synthesis and application | |
| FR2978151A1 (en) | P-CHIROGENIC ORGANOPHOSPHORUS COMPOUNDS | |
| EP0443923B1 (en) | New aminophosphine-phosphinites, their process and their use for enantio-selective reactions | |
| Turcry et al. | Aminophosphine phosphinite (AMPP) and enantioselective hydrogenation of ketones: further developments | |
| US3733356A (en) | Process for the preparation of cis-1-propenylphosphonic acid | |
| Yan et al. | Asymmetric Hydroformylation of Olefins Catalyzed by a Chiral Diphosphite‐Rhodium Complex | |
| JPH1143452A (en) | Improvement of quality of alcohol |