WO2015063790A1 - Catalyseur pour hydrogénation asymétrique par transfert de cétones et d'imines - Google Patents

Catalyseur pour hydrogénation asymétrique par transfert de cétones et d'imines Download PDF

Info

Publication number
WO2015063790A1
WO2015063790A1 PCT/IN2014/000680 IN2014000680W WO2015063790A1 WO 2015063790 A1 WO2015063790 A1 WO 2015063790A1 IN 2014000680 W IN2014000680 W IN 2014000680W WO 2015063790 A1 WO2015063790 A1 WO 2015063790A1
Authority
WO
WIPO (PCT)
Prior art keywords
transfer hydrogenation
methyl
amino
asymmetric transfer
catalyst
Prior art date
Application number
PCT/IN2014/000680
Other languages
English (en)
Inventor
Ashutosh ANANT KELKAR
Sudhindra HANAMANT DESHPANDE
Savita KIRAN SHINGOTE
Vaishali SARJERAO SHENDE
Original Assignee
Council Of Scientific And Industrial Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Council Of Scientific And Industrial Research filed Critical Council Of Scientific And Industrial Research
Publication of WO2015063790A1 publication Critical patent/WO2015063790A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/822—Rhodium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/827—Iridium

Definitions

  • the present invention relates to a catalyst composition comprising a ligand with a metal complex. More particularly, the present invention relates to a catalyst composition comprising a ligand of formula I,
  • Catalytic asymmetric transfer hydrogenation of ketones is one of the important transformations in organic chemistry and a large number of catalytic methods are available to achieve this goal. This reduction has become subject of considerable interest from both academic as well as industrial point of view.
  • the complex derived from the N"-Bn derivative of TsDPEN reduces monocyclic imines in up to 60% ee, whilst the N ' -Me derivative of TsDPEN forms a more active catalyst than the non- alkylated analogue and reduces ketones in up to 97% ee.
  • US patent Pub. No. US 2003/0199713 Al discloses a catalyst for the asymmetric hydrogenation represented by the formula ML a XbS c , where M is a transition metal, to be chosen from Rh and Ru, and X is a counter ion and S is a ligand, 'a' ranges from .5 to 3, 'b' and 'c', each independently, range from 0 to 2, and L is a chiral ligand having formula (1), where C n together with the two 2 O-atoms and the P-atom forms a substituted or non- substituted ring with 2-4 C-atoms, R 1 and R 2 each independently represent H, an optionally substituted alkyl, aryl, alkaryl or aralkyl group or.
  • TsDPEN and TsCYDN ligands are used not only in organic media but also in water and under aerobic conditions.
  • TsDPEN ligands in combination of ruthenium, rhodium and iridium in water as media and sodium format as hydrogen donor can be effectively used for ATH of ketones with 99% conversion and more than 92% ee whereas TsCYDN are proved to be better ligands than TsDPEN, as far as rhodium catalyst is concerned, with high conversion and ee are observed within a very short time of 10 mins tolh for many ketones.
  • a variety of amino alcohols ligands are designed and synthetized for ATH of ketones, with different electronic and steric properties but the structurally versatile monosulfonated diamine ligands are less reported and most reports are restricted on modifying the substitution on either on sulfonamide group or on the phenyl group without disturbing the real C2 Symmetric backbone of TsDPEN or TsCYDN.
  • Rh-TsCYDN shows better activity than Rh- TsDPEN.
  • metal complex and ligand combination since Ru-TsDPEN shows better results than Ru-TsCYDN whereas Rh-TsCYDN shows better activity than Rh- TsDPEN.
  • the main object of the present invention is to provide a catalyst composition comprising a ligand of formula I,
  • the present invention provides a catalyst composition comprising a ligand of formula I,
  • CF3Ts (4-(trifluoromethyl)phenyl-l- sulfonyl, S0 2 - C 6 H4-CF3)]with a metal catalyst, wherein said metal is selected from transition metals, preferably Ru, Rh or Ir.
  • Fig. 1 depicts Effect of methanol content in water on ATH of l-methyl-6,7- dimethoxy-3,4-dihydroxisoquinoline(la): 25% MeOH in water (A), 50% MeOH in water ( ⁇ ), 75% MeOH in water ( ⁇ ); la (0.5 mmol); HCOONa (2.5 mmol); temp: 40 C, solvent: 2 ml.
  • Fig.2 depicts the conversion profile of 1 -methyl- 6,7-dimethoxy-3,4- dihydroxisoquinoline(la) with regard to time with the reaction conditions of la (0.5 mmol), [Rh(Cp*)C12]2 (0.0025 mmol), (I S, 2S)-TsDPEN (0.0075 mmol), HCOONa (2.5 mmol), 40°C, solvent (2 ml), H20/ MeOH ( v/v, 1 : 1); Conv ( ⁇ ), ee (( ⁇ )
  • the present invention provides a catalyst composition comprising a ligand of formula
  • R is selected from the group consisting of phenyl, substituted phenyl, alkyl- linear or branched;R 2 is alkyl-linear or branched;
  • R 3 , R 4 are independently selected from amino, NHTs or NHCF 3 Ts; with a metal catalyst, wherein said metal is selected from transition metals, preferably Ru,Rhorlr.
  • the present invention provides a catalyst composition comprising a ligand of formula I,
  • R 1 is selected from the group consisting of phenyl, substituted phenyl,alkyl- linear or branched;R is alkyl-linear or branched; R 3 , R 4 are independently selected from amino, NHTs or NHCF 3 Ts; with a metal catalyst, wherein said metal is selected from transition metals, preferably Ru,RhorIr.
  • the present invention provides a catalyst composition wherein the Ligand is preferably selected from N-[(lR,2S)-2-amino-l-phenylpropyl]-4- methyl benzene sulfonamide ⁇ ),
  • the present invention provides a catalyst composition, wherein the ⁇ metal catalyst is preferably selected from Pentamethylcyclopentadienylrhodium (III) chloride dimer, [Rh (Cp*) Cl 2 ] 2 , Pentamethylcyclopentadienyliridium(III) chloridedimer, [Ir(Cp*)Cl 2 ] 2 orDichloro (p-cymene) ruthenium (II) dimer [Ru (p-cymene) Cl 2 ] 2 .
  • the ⁇ metal catalyst is preferably selected from Pentamethylcyclopentadienylrhodium (III) chloride dimer, [Rh (Cp*) Cl 2 ] 2 , Pentamethylcyclopentadienyliridium(III) chloridedimer, [Ir(Cp*)Cl 2 ] 2 orDichloro (p-cymene) ruthenium (II) dimer [Ru (p
  • the invention encompasses synthesis of novel ligands of formula I, preferably the synthesis of ligands 3, 7, 13 and 14 are exemplified.
  • the present invention provides a process for asymmetric transfer hydrogenation of ketones in water or water-co-solvent mixture using sodium formate as a hydrogen donor.
  • the co solvent is preferably selected from the group consisting of methanol, ethanol, n-propanol, n-butanol, isopropanol, ethylene glycol, DMF, DMSO, NMP, 1,4- dioxane, THF, acetonitrile or combinations thereof.
  • the present invention provides a process for asymmetric transfer hydrogenation of ketones is carried out with FA/TEA (formic acidVtriethylarnine mixture)as hydrogen donor as well as solvent or with water as a solvent.
  • FA/TEA formic acidVtriethylarnine mixture
  • the present invention provides a process for asymmetric transfer hydrogenation of imines in water or water-co-solvent mixture using sodium formate as a hydrogen donor.
  • the co solvent is preferably selected from the group consisting of methanol, ethanol, n-propanol, n-butanol, isopropanol, ethylene glycol, DMF, DMSO, NMP, 1,4- dioxane, THF, acetonitrile or combinations thereof.
  • the preferred co-solvents are selected from acetonitrile or methanol.
  • the present invention provides a process for asymmetric transfer hydrogenation of imines is carried out with FA/TEA as hydrogen donor with organic solvent as cnsolvent.
  • the organic solvent is preferably selected from the group consisting of methanol, ethanol, n-propanol, n-butanol, isopropanol, ethylene glycol, DMF, DMSO, NMP, 1,4-dioxane, THF, acetonitrile or combinations thereof.
  • the invention provides a solvent system that is suitable for hydrogenation of iniines asymmetric transfer hydrogenation.
  • asymmetric transfer hydrogenation of l-methyl-6,7-dimethoxy-3,4-dihydroxisoquinoline(an imine) is carried out using [Rh(Cp*)C12]2and (1S,2S)-TSDPEN, a known ligand, with sodium formate as hydrogen donor in water and in presence of various co-solvents selected from the group consisting of water, methanol, ethanol, n-propanol, n-butanol, isopropanol, ethylene glycol, DMF, DMSO, NMP, 1,4-dioxane, THF, acetonitrile or combinations thereof as reported in tables 6 and 7.
  • NMR spectra were recorded on a 400 MHz Bruker spectrometer.
  • HPLC analysis was carried out using Waters Perkin Elmer HPLC instrument with quaternary gradient pump, diode array detector and auto sampler.
  • GC-MS analysis was carried out using Agilent 5973 instrument using HP-5 column purchased from Agilent Technologies.HR-MS analysis was done using Agilent 6520 Q-TOFinstrument.
  • the ligand is prepared as per the scheme2.
  • 1R,2S norephedrine (3.0g, 20 mmol) compound l,triphenylphosphine (5.2g,20 mmol) and BOc protected p-toluene sulfonyl amide (5.42g,20 mmol)
  • dichloromethane 60ml
  • DEAD 3.46g, 20 mmol
  • reaction mass was washed with mixture of IN HC1 (5ml) and water (20 ml). 4N HC1 in dioxane (20ml) was added and the reaction was heated at 50°C for 2 h. The reaction mass after heating was evaporated to dryness and dichloromethane (50 ml) and water (50 ml) was added to it. The layers were shaked vigorously and DCM layer was discarded. Aqueous layer was neutralized by slow drop wise addition of dilute NaOH (4N), till the solution pH reached 7. The white solids precipitated were allowed to digest overnight and then filtered over sinteredglass crucible.
  • the ligand 13 and 14 is prepared by the scheme 5 are detailed herein below, i) Synthesis of (IS, 2S)-l-chloro-l-phenyl-propan-2-amine.
  • Compound 8 In a 3 necked round bottom flask 1R, 2S norephedrine hydrochloride(30.0g, 200 mmol) was taken and to it, thionyl chloride (70.9g 596mmol) was added drop wise. After the addition was complete the reaction mixture was stirred for 3h. Vacuum was applied to remove the excess thionyl chloride, and then acetone (50 ml) was slowly added to the slurry. The resultant solution was filtered and washed with acetone and recrystalised from methanol to obtain white solids of compound 8(22 g, yield 67%)
  • step (i) The compound 8 (10.0 g, 50mmol) obtained from step (i) was dissolved in methanol (40 ml).2N NaOH (20 ml) was slowly added under stirring to the methanol solution. The mixture was further stirred for 4h, and then was concentrated to 20ml. The aqueous layer was cooled to get the crystals of aziridine. The solution was filtered and washed 2-3 times with water (10 ml). Light yellow crystals of aziridine compound 9 (5g,76%yield)were obtained after recrystallization from hexane.
  • Table 3 Screening of ligands and catalyst for ATH of ketones using FA/TEA as hydrogen transfer agent in water Formic acid : TEA and water
  • Table 4 Screening of ligands and catalyst for ATH of imines using FA/TEA as hydrogen transfer agent and acetonitrile as solvent

Abstract

L'invention concerne une composition de catalyseur comprenant un ligand représenté par la formule I qui permet d'effectuer une hydrogénation asymétrique par transfert de >C=0, >C=C< ou >C=N, R1 étant sélectionné dans le groupe constitué par phényle, phényle substitué, R2 représentant alkyle linéaire ou ramifié, et R3, R4 étant sélectionnés indépendamment parmi amino, NHTs ou NHCF3Ts, au moyen d'un catalyseur métallique dans lequel le métal est un métal de transition sélectionné de préférence parmi Ru, Rh ou Ir.
PCT/IN2014/000680 2013-11-01 2014-10-27 Catalyseur pour hydrogénation asymétrique par transfert de cétones et d'imines WO2015063790A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3240/DEL/2013 2013-11-01
IN3240DE2013 2013-11-01

Publications (1)

Publication Number Publication Date
WO2015063790A1 true WO2015063790A1 (fr) 2015-05-07

Family

ID=52273377

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2014/000680 WO2015063790A1 (fr) 2013-11-01 2014-10-27 Catalyseur pour hydrogénation asymétrique par transfert de cétones et d'imines

Country Status (1)

Country Link
WO (1) WO2015063790A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113941365A (zh) * 2021-10-11 2022-01-18 南开沧州渤海新区绿色化工研究有限公司 用于芳香酮不对称氢转移反应的温敏催化剂及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030199713A1 (en) 2000-07-07 2003-10-23 Michel Berg Van Den Catalyst for asymmetric (transfer) hydrogenation
WO2010106364A2 (fr) * 2009-03-17 2010-09-23 Johnson Matthey Public Limited Company Procédé
US20100261924A1 (en) * 2009-04-10 2010-10-14 Kanto Kagaku Kabushiki Kaisha Asymmetric catalyst and process for preparing optically active alcohols using the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030199713A1 (en) 2000-07-07 2003-10-23 Michel Berg Van Den Catalyst for asymmetric (transfer) hydrogenation
WO2010106364A2 (fr) * 2009-03-17 2010-09-23 Johnson Matthey Public Limited Company Procédé
US20100261924A1 (en) * 2009-04-10 2010-10-14 Kanto Kagaku Kabushiki Kaisha Asymmetric catalyst and process for preparing optically active alcohols using the same

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
CHAOQUN LI; JIANLIANG XIAO: "Asymmetric Hydrogenation of Cyclic ,Imines with an Ionic Cp*Rh (III) Catalyst", J. AM. CHEM. SOC., vol. 130, 2008, pages 13208 - 13209, XP055171341, DOI: doi:10.1021/ja8050958
JINCHENG MAO; JUN GUO: "Chiral Amino Amides for the Ruthenium (II)-Catalyzed Asymmetric Transfer Hydrogenation Reaction of Ketones in Water", CHIRALITY, vol. 22, 2010, pages 173 - 181, XP055099083, DOI: doi:10.1002/chir.20723
JOSÉ E. D. MARTINS ET AL: "Ru(II) Complexes of N-Alkylated TsDPEN Ligands in Asymmetric Transfer Hydrogenation of Ketones and Imines", ORGANIC LETTERS, vol. 11, no. 4, 19 February 2009 (2009-02-19), pages 847 - 850, XP055171318, ISSN: 1523-7060, DOI: 10.1021/ol802801p *
JOSE E. D. MARTINS; GUY J. CLARKSON; MARTIN WILLS: "Ru(II) Complexes of N-Allcylated TsDPEN Ligands in Asymmetric Transfer Hydrogenation of Ketones and Imines", ORGANIC LETTERS, vol. 11, no. 4, 2009, pages 847 - 850, XP055171318, DOI: doi:10.1021/ol802801p
JOSE E. D. MARTINS; MIGUEL A. CONTRERAS REDONDO; MARTIN WILLS: "Applications ofN'-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of C=O and C=N bonds", TETRAHEDRON: ASYMMETRY, vol. 21, 2010, pages 2258 - 2264
MARTINS J E D ET AL: "Applications of N'-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of C?O and C?N bonds", TETRAHEDRON ASYMMETRY, PERGAMON PRESS LTD, OXFORD, GB, vol. 21, no. 18, 27 September 2010 (2010-09-27), pages 2258 - 2264, XP027307544, ISSN: 0957-4166, [retrieved on 20100731] *
OLALLA NIETO FAZA ET AL: "Noyori Hydrogenation: Aromaticity, Synchronicity, and Activation Strain Analysis", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 78, no. 11, 7 June 2013 (2013-06-07), pages 5669 - 5676, XP055171357, ISSN: 0022-3263, DOI: 10.1021/jo400837n *
XIAOFENG WU; JIANKE LIU; XIAOHONG LI; ANTONIO ZANOTTI-GEROSA; FRED HANCOCK; DANIELE VINCI; JIWU RUAN; JIANLIANG XIAO: "On Water and in Air: Fast and Highly Chemo selective Transfer Hydrogenation of Aldehydes with Iridium Catalysts", ANGEW. CHEM., vol. 118, 2006, pages 6870 - 6874

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113941365A (zh) * 2021-10-11 2022-01-18 南开沧州渤海新区绿色化工研究有限公司 用于芳香酮不对称氢转移反应的温敏催化剂及其制备方法
CN113941365B (zh) * 2021-10-11 2023-09-01 南开沧州渤海新区绿色化工研究有限公司 用于芳香酮不对称氢转移反应的温敏催化剂及其制备方法

Similar Documents

Publication Publication Date Title
Malkov et al. Formamides derived from N-methyl amino acids serve as new chiral organocatalysts in the enantioselective reduction of aromatic ketimines with trichlorosilane
Clavier et al. Recent developments in enantioselective metal‐catalyzed domino reactions
CN103080072B (zh) 制备可用于生产nep抑制剂的中间体的新方法
Babazadeh et al. Transition metal-catalyzed [2+ 2+ 2] cycloaddition of nitrogen-linked 1, 6-diynes: a straightforward route to fused pyrrolidine systems
Pindi et al. N‐Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N‐Phosphinyl Imines and their Application to Asymmetric aza‐Henry Reaction
Tang et al. Synthesis of a water-soluble cationic chiral diamine ligand bearing a diguanidinium and application in asymmetric transfer hydrogenation
Li et al. Highly stereoselective direct aldol reactions catalyzed by a bifunctional chiral diamine
RU2446154C2 (ru) Сульфонилированные дифенилэтилендиамины, способ их получения и применение в катализе гидрирования с переносом водорода
Wu et al. Development of highly enantioselective new Lewis basic N-formamide organocatalysts for hydrosilylation of imines with an unprecedented substrate profile
JP2010512379A (ja) プロセス
ES2552022T3 (es) Procedimiento de preparación de un derivado de 3,4-dihidro-isoquinolina trisustituido enantiomérico
Martins et al. Ir (III) complexes of diamine ligands for asymmetric ketone hydrogenation
Roszkowski et al. Selected recent developments in the enantioselective reduction of imines by asymmetric transfer hydrogenation
ES2375334T3 (es) Compuesto de 3,4-dihidro-1h-isoquinolina trisubstituida, procedimiento para su preparación y su uso.
WO2015063790A1 (fr) Catalyseur pour hydrogénation asymétrique par transfert de cétones et d&#39;imines
US9328079B2 (en) Process for producing optically active amine
KR100306964B1 (ko) 광학활성인디아민헥사논유도체의제조방법
Burtoloso et al. Asymmetric synthesis of cis-2, 4-disubstituted azetidin-3-ones from metal carbene chemistry
JP5042438B2 (ja) シン立体配置を有するβ−アミノアルコール類の製造方法
Puleo et al. Substrate control by means of the chiral cavity of prolinamide derivatives of cholic acid in the organocatalyzed Michael addition of cyclohexanone to nitroolefins
EP3609859B1 (fr) Composés complexes métalliques chiraux
JP5344523B2 (ja) 立体選択的にストレッカー反応を進行させ得る触媒、およびそれを用いたα−アミノニトリル誘導体を立体選択的に製造するための方法
CN101243100A (zh) 二茂铁-二膦配体
CN107540623B (zh) 一种高对映选择性C-5位α-立体中心4-硝基异恶唑醇类化合物、其制备方法及应用
CN107540616B (zh) 一种高对映选择性吡唑胺化合物的制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14821298

Country of ref document: EP

Kind code of ref document: A1

DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14821298

Country of ref document: EP

Kind code of ref document: A1