+

WO2017193288A1 - Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse - Google Patents

Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse Download PDF

Info

Publication number
WO2017193288A1
WO2017193288A1 PCT/CN2016/081589 CN2016081589W WO2017193288A1 WO 2017193288 A1 WO2017193288 A1 WO 2017193288A1 CN 2016081589 W CN2016081589 W CN 2016081589W WO 2017193288 A1 WO2017193288 A1 WO 2017193288A1
Authority
WO
WIPO (PCT)
Prior art keywords
membered
mmol
alkyl
aryl
group
Prior art date
Application number
PCT/CN2016/081589
Other languages
English (en)
Inventor
Fuk Yee Kwong
Pui Ying CHOY
Yinuo WU
Qingjing Yang
Original Assignee
The Hong Kong Polytechnic University Shenzhen Research Institute
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 The Hong Kong Polytechnic University Shenzhen Research Institute filed Critical The Hong Kong Polytechnic University Shenzhen Research Institute
Priority to PCT/CN2016/081589 priority Critical patent/WO2017193288A1/fr
Publication of WO2017193288A1 publication Critical patent/WO2017193288A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
    • B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
    • C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • 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
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • 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
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
    • B01J2231/4227—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group with Y= Cl
    • 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
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
    • 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
    • B01J2531/824—Palladium
    • 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
    • B01J2540/00—Compositional aspects of coordination complexes or ligands in catalyst systems
    • B01J2540/40—Non-coordinating groups comprising 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
    • B01J2540/00—Compositional aspects of coordination complexes or ligands in catalyst systems
    • B01J2540/60—Groups characterized by their function
    • B01J2540/62—Activating groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • C07C2531/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • C07C2531/24—Phosphines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/24—Anthracenes; Hydrogenated anthracenes

Definitions

  • the present invention relates to a series of novel linked indolyl phosphine ligands for transition metals, the synthesis thereof and their use in catalytic reactions.
  • the disclosed method provides improvements of transition-metal-catalyzed reactions, including the range of substrates scope, reaction conditions, and efficiency. For examples, remarkable improvements have been realized in the preparation of sterically hindered biaryl compounds by transition-metal-catalyzed cross-coupling reactions.
  • Transition-metal-catalyzed cross-coupling reactions have received significant attention and became an extremely versatile protocol in organic synthesis for the connection of two different fragments via the formation of either carbon-carbon and/or carbon-heteroatom bonds (de Meijere, A. ; Brase, S. ; Oestreich, M. Eds. Metal-Catalyzed Cross-Coupling Reactions, Vol. 3: Wiley-VCH, Weinheim, 2013. Colacot, T.J. Eds. New Trends in Cross-Coupling, Theory and Applications: Royal Society of Chemistry, Cambridge, 2015) .
  • Suzuki-Miyaura coupling is one of the preeminent methods of the formation of carbon-carbon bonds and has been used in the construction of diversified biaryls, and they have a myriad of applications in pharmaceutical, materials, and agricultural chemistry (Miyaura, N. Topics in Current Chemistry, 2002, 219, 11) .
  • Arylamines are frequently encountered in natural and pharmaceutical products.
  • Buchwald-Hartwig amination is a highly valuable method for the formation of carbon-nitrogen bond (Ricci, A Ed Modern Amination Methods: Wiley-VCH, Weinheim, 2000) .
  • ligands play essential roles during each step of the catalytic cycle including oxidative addition, transmetallation, and reductive elimination.
  • the structural features of the ligands can greatly influence the reaction rate, regioselectivity, and stereoselectivity of the cross-coupling reaction.
  • the strategic design of ligands with appropriate steric/electronic natures and great diversity is crucial in dealing with challenging and problematic substrates in this area.
  • sterically hindered substrates and a further decrease of the catalyst loading remain great challenges.
  • the present invention relates to a series of novel and efficient linked indolyl phosphine ligands for transition metals, to their preparation and to their use in catalytic reactions.
  • the disclosed method provides improvements of transition-metal-catalyzed reactions, including the range of substrates scope, reaction conditions, and efficiency.
  • the linked indolyl phosphine ligands several reactions can be effectively handled such as Suzuki-Miyaura, Heck, Sonogashira, Hiyama, Stille cross-coupling reactions; Buchwald-Hartwig amination; direct arylation; and cyanation with aryl halides or vinyl halides.
  • the basic indolyl phosphines bearing tunable linkage can be prepared via traditional Fischer Indolization protocol.
  • a combination of phenylhydrazines and acetophenones provides a high diversification of the ligand structure.
  • the ligands are suitable to use as scaffolds in metal-ligand complexes, which can serve as catalysts for further reactions.
  • the ligands can be prepared in a large scale, and purified by simple recrystallization. These ligands can exhibit exceptionally high stability in both solid and solution states.
  • the present invention relates to indolyl phosphine ligands bearing tunable linkage, and methods of making such utilizing phenylhydrazine and acetophenones as the starting materials with various linkage reagents.
  • the present invention further includes uses of the ligands in the synthesis of pharmaceuticals, materials, and agriculture.
  • the present invention is achieved according to the novel phosphine ligands structure formula (I) , below:
  • Y independently represents an oxygen atom or C-R 8 group or NR 8 group and R 1 for each of the two R 1 groups independently of the other represents C 1 -C 8 -alkyl; C 3 -C 10 -cycloalkyl, which includes especially both monocyclic and also bi-and tri-cyclic cycloalkyl; (5-to 11-membered) heterocycloalkyl; CF 3 ; ferrocenyl; C 5 -C 20 -aryl, which includes especially the phenyl, naphthyl, fluorenyl; (5-to 11-membered) heteroaryl, wherein the number of hetero atoms, selected from the group N, O, S, may be from 1 to 2; wherein the two R 1 may also be linked to one another; or wherein each such C 3 -C 10 -cycloalkyl, (5-to 11-membered) heterocycloalkyl, C 6 -C 20 -aryl or (5-to 11-membered
  • substituents independently of one another, may be hydrogen, C 1 -C 20 -alkyl, C 2 -C 20 -alkenyl, C 3 -C 8 -cycloalkyl, C 2 -C 9 -heteroalkyl, C 5 -C 10 -aryl, C 2 -C 9 -heteroaryl, wherein the number of heteroatoms, especially from the group N, O, S, may be from 1 to 4; C 1 -C 14 -alkoxy, preferably -O (C 1 -C 6 ) alkyl, particularly preferably OMe; C 1 -C 10 -halo-alkyl, preferably CF 3 , hydroxyl, secondary, tertiary amino groups; wherein two of the mentioned substituents may also bridged with one another to form 4-to 8-membered ring which can be further substituted preferably by linear or branched C 1 -C 10 -alkyl, C 6 -aryl, benzyl
  • R 2 , R 3 , R 4 , and R 5 are each independently selected from the group comprising hydrogen; halogen; C 1 -C 10 -alkyl; hydroxyl; -O (C 1 -C 6 ) alkyl; CF 3 ; C 3 -C 10 -cycloalkyl; (5-to 11-membered) heterocycloalkyl; amino; silyloxy; sulfhydryl; alkylthio; thioalkyl; phosphoryl; phosphonate; phosphine; urea; thiourea; nitrile; carbonyl; carboxyl; carboxamide; C 6 -C 20 -aryl; (5-to 11-membered) heteroaryl, wherein the number of hetero atoms, selected from the group N, O, S, may be from 1 to 2; wherein any two or more adjacent instances of R 2 , R 3 , R 4 , and R 5 , taken together with the carbons to which they are
  • R 9 , R 10 , R 11 , and R 12 are each independently selected from the group comprising hydrogen; halogen; C 1 -C 10 -alkyl; hydroxyl; –O (C 1 -C 6 ) alkyl; CF 3 ; C 3 -C 10 -cycloalkyl; (5-to 11-membered) heterocycloalkyl; amino; silyloxy; sulfhydryl; alkylthio; thioalkyl; phosphoryl; phosphonate; phosphine; urea; thiourea; nitrile; carbonyl; carboxyl; carboxamide; C 6 -C 20 -aryl; (5-to 11-membered) heteroaryl, wherein the number of hetero atoms, selected from the group N, O, S, may be from 1 to 2; wherein any two or more adjacent instances of R 9 , R 10 , R 11 , and R 12 , taken together with the carbons to which they are
  • n is independently for each occurrence an integer in the range 1 to 8 inclusive, and the ligand is achiral or, when chiral, is a single stereoisomer or a mixture of stereoisomers.
  • the invention relates to formula (I) , wherein one of the R 1 is C 1 -C 8 -alkyl selected from –CH 3 , –CH 2 CH 3 , –C (CH 2 ) 2 CH 3 , –CH (CH 3 ) 2 , –C (CH 3 ) 3 , – C (CH 2 CH 3 ) 3 , –C (CH 2 CH 3 ) (CH 3 ) 2 , and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are as defined in the first aspect.
  • the invention relates to formula (I) , wherein one of the R 1 is C 3 -C 10 -cycloalkyl, which includes especially both monocyclic and also bi-and tri-cyclic cycloalkyl, selected from cyclopentyl, cyclohexyl, 1-adamantyl, and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are as defined in the first aspect.
  • the invention relates to formula (I) , wherein one of the R 1 is C 6 -C 20 -aryl selected from phenyl, 2-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3, 5-di (fluoromethyl) phenyl, 3, 5-di-tert-butylphenyl, 4-methoxyphenyl, 2-trifluoromethylphenyl, 2, 4, 6-trimethylphenyl, 3, 5-di-tert-butyl-4-methoxyphenyl, and naphthyl, and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are as defined in the first aspect.
  • the present invention provides a process for the preparation of the above-described ligands of formula (I) .
  • the ligands can be prepared by traditional Fischer Indolization followed the general reaction scheme 1 below.
  • the novel phosphine ligands bearing tunable linkage are used as catalysts in combination with transition metal complexes.
  • the transition metal compounds used are particularly preferably palladium compounds.
  • the ligands according to the invention can generally be added in situ to corresponding transition metal precursor compounds and accordingly used for catalytic applications. However, it may occasionally be advantages for specific phosphine complexes of the mentioned transition metals to be prepared first and subsequently used as catalyst to increase the catalytic activity.
  • the phosphine ligands bearing tunable linkage prepared in accordance with the invention have proved suitable especially as the ligand component for the biaryl synthesis from aryl halides or vinyl halides.
  • catalyst compositions contain a ligand described herein and a transition metal compound.
  • transition metal compounds include those of palladium, rhodium, ruthenium, platinum, gold, cobalt, iridium, copper, and nickel, as well as combinations.
  • the transition metal compound and the ligand are provided in the catalyst composition in stoichiometric amounts with respect to one other.
  • the optimum ligand to metal ratio depends on the metal source used as well as the specifics of the transformation being attempted.
  • the transition metal compound is provided in the catalyst composition as a salt of a central atom.
  • a non-limiting example of such a salt is an acetate salt.
  • a preferred transition metal compound is palladium acetate, or Pd (OAc) 2 .
  • a catalyst composition is then formed of a mixture of palladium acetate and a ligand compound coordinated as a complex as described herein.
  • Other embodiments of palladium sources formally in the 2+ oxidation state include but are not limited to PdCl 2 , Pd (TFA) 2 , Pd (CH 3 CN) 4 (BF 4 ) 2 and PdCl 2 (CH 3 CN) 2 .
  • the transition metal compound is in zero valence state.
  • An example is tris (dibenzylideneacetone) dipalladium (0) , commonly abbreviated as Pd 2 (dba) 3 .
  • Other palladium sources in formally the zero or other valence states may also be suitable. Examples include but are not limited to Pd (dba) 2 .
  • the ligands described herein exhibit utility in transition metal catalyzed reactions.
  • the disclosed ligands may be combined with a variety of transition metal compounds to catalyze a range of chemical transformations.
  • compositions containing a transition metal compound and a disclosed ligand can be used to catalyze a variety of organic reactions.
  • a non-limiting example of a reaction catalyzed by a disclosed ligand is given in Scheme I, illustrating the catalysis of a C-N reaction.
  • Other reactions of interest include carbon-oxygen, carbon-carbon.
  • the catalysts can be used to catalyze Suzuki-Miyaura type C-C bond-forming reactions, Buchwald-Hartwig Amination C-N bond forming reactions, direct arylation C-C bond forming reactions, and Hiyama type C-C bond forming reactions.
  • a combination of a ligand with a transition metal compound catalyzes the following reactions:
  • the present invention provides a process for the preparation of the above-described ligands.
  • These ligands may be prepared in the manner depicted in the general reaction Scheme 1.
  • Method A follows the general procedures of Fischer-indole synthesis, compound II can be obtained from corresponding substituted acetophenone (100 mmol) , corresponding substituted phenylhydrazine (110 mmol) and polyphosphoric acid (PPA) as an off-white solid.
  • Compound II from Method A may be made in the manner described by Kwong, Organic Syntheses 2016, 93, 14-28.
  • Method B According to the literature, compound II can be obtained from corresponding substituted oxindole (50 mmol) , 2-chloropyridine (60 mmol) , trifluoromethanesulfonic anhydride (60 mmol) and corresponding substituted 2-naphthol (50 mmol) as a grey solid.
  • Compound II from Method B may be made in the manner described by Ghandi, Tetrahedron Letters 2011, 270-273; and Shibata, Organic Letters 2013, 15, 686-689.
  • Example 5-6 Catalysis Examples –Suzuki-Miyaura Couplings
  • Pd (II) source and ligand were loaded into a Schlenk tube equipped with a Teflon-coated magnetic stir bar. The tube was evacuated and flushed with nitrogen for three cycles. Precomplexation was applied by adding freshly distilled dichloromethane and Et 3 N into the tube. The palladium complex stock solution was stirred and warmed using hair drier for about 1 to 2 minutes until the solvent started boiling. The solvent was then evaporated under high vacuum.
  • Aryl chloride (0.5 mmol) , boron source (1.0 mmol) , and base (1.5 mmol) were then added to Schlenk tubes. 1.0 mL of solvent was added (to rinse the tube wall) with stirring at room temperature for several minutes. The tube was then placed in a preheated oil bath and stirred for 12-24 hours. After the completion of reaction as judged by GC or TLC analysis, the reaction was cooled down to room temperature and quenched with water and diluted with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (230-400 mesh) to afford the desired product.
  • a stock solution of Pd 2 (dba) 3 (1.0 mol%, 0.0023 g) with L3 (4.0 mol%, 0.0099 g) in freshly distilled dioxane (5.0 ml) was initially prepared by continuously stirring at room temperature for 10 min. 1 ml of the stock solution was transferred to another nitrogen-filled tube for further dilution. Freshly distilled dioxane was then added to the tube to give the needed concentration of palladium complex in total 4 ml final solution volume.
  • 2-Chloro-1, 3-dimethylbenzene 0.5 mmol, 0.07 g)
  • (2-ethylphenyl) boronic acid 1.0 mmol, 0.15 g, 2.0 equiv.
  • Table 1 Summary of the optimaization of the results of Catalysis Experiment 1 a
  • Pd 2 (dba) 3 (1.0 mol%, 0.0023 g) and L3 (4.0 mol%, 0.0099 g) were loaded into a Schlenk tube equipped with a magnetic stir bar. The tube was carefully evacuated and backfilled with nitrogen (3 cycles) . Precomplexation was applied by adding freshly distilled dioxane (0.5 ml) into the tube. The palladium complex stock solution was continuously stirred at room temperature for 10 min. 2-Chloro-1, 3, 5-trimethylbenzene (0.5 mmol, 0.077 g) , potassium 2, 6-dimethylphenyltrifluoroborate (1.0 mmol, 0.21 g, 2.0 equiv.
  • Example 7-10 Catalysis Examples –General Cross-Couplings
  • Example 8 Catalytic Hiyama Cross-coupling Reaction of aryl chlorides and aryl trialkoxysilanes
  • Example 9 Catalytic direct arylation of aryl chlorides and polyfluoroarene
  • Example 10 Catalytic Borylation of aryl chlorides and boron reagents

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Catalysts (AREA)

Abstract

L'invention concerne une série de nouveaux ligands d'indolyle phosphine liés pour des métaux de transition, leur synthèse et leur utilisation dans des réactions de couplage catalytique. Les ligands permettent d'obtenir des améliorations de réactions catalysées par le métal de transition, comprenant la plage des substrats, des conditions de réaction et de l'efficacité.
PCT/CN2016/081589 2016-05-10 2016-05-10 Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse WO2017193288A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2016/081589 WO2017193288A1 (fr) 2016-05-10 2016-05-10 Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2016/081589 WO2017193288A1 (fr) 2016-05-10 2016-05-10 Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse

Publications (1)

Publication Number Publication Date
WO2017193288A1 true WO2017193288A1 (fr) 2017-11-16

Family

ID=60266154

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/081589 WO2017193288A1 (fr) 2016-05-10 2016-05-10 Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse

Country Status (1)

Country Link
WO (1) WO2017193288A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110423220A (zh) * 2019-06-05 2019-11-08 维思普新材料（苏州）有限公司 一种9-苯基吖啶类化合物的制备方法
CN116396302A (zh) * 2023-04-10 2023-07-07 南京工业大学 一种吲哚类化合物及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5886182A (en) * 1997-12-10 1999-03-23 The Hong Kong Polytechnic University Chiral pyridylphosphines and their application in asymmetric catalytic hydrogenation of 2-arylpropenoic acids
CN104945434A (zh) * 2015-06-19 2015-09-30 香港理工大学深圳研究院 (2﹣二取代膦苯基)-1-烷基-吲哚膦配体及其合成方法和应用
CN105152827A (zh) * 2015-08-12 2015-12-16 香港理工大学深圳研究院 芳基磺酸酯类底物与有机钛的交叉偶联反应

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5886182A (en) * 1997-12-10 1999-03-23 The Hong Kong Polytechnic University Chiral pyridylphosphines and their application in asymmetric catalytic hydrogenation of 2-arylpropenoic acids
CN104945434A (zh) * 2015-06-19 2015-09-30 香港理工大学深圳研究院 (2﹣二取代膦苯基)-1-烷基-吲哚膦配体及其合成方法和应用
CN105152827A (zh) * 2015-08-12 2015-12-16 香港理工大学深圳研究院 芳基磺酸酯类底物与有机钛的交叉偶联反应

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHAU MING SO ET AL.: "Suzuki-Miyaura coupling of Aryl Tosylates Catalyzed by an Array of Indolyl Phosphine-Palladium Catlysts", J.ORG.CHEM, vol. 73, no. 19, 9 November 2008 (2008-11-09), pages 7731 - 7734, XP055232654, Retrieved from the Internet <URL:doi:10.1021/jo8014819> *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110423220A (zh) * 2019-06-05 2019-11-08 维思普新材料（苏州）有限公司 一种9-苯基吖啶类化合物的制备方法
CN116396302A (zh) * 2023-04-10 2023-07-07 南京工业大学 一种吲哚类化合物及其制备方法

Similar Documents

Publication Publication Date Title
CA2267153C (fr) Synthese d&#39;ethers d&#39;aryle, procedes et reactifs afferents
US7250510B2 (en) Transition metal complexes of N-heterocyclic carbenes, method of preparation and use in transition metal catalyzed organic transformations
CN102947000A (zh) 羧基化催化剂
Shen et al. Synthesis of polyfluoroarene-substituted benzofuran derivatives via cooperative Pd/Cu catalysis
Wang et al. Phosphine‐Free, Efficient Double Carbonylation of Aryl Iodides with Amines Catalyzed by Water‐Insoluble and Water‐Soluble N‐Heterocyclic Carbene–Amine Palladium Complexes
Seva et al. Palladium biphenyl N-heterocyclic carbene complexes: Synthesis, structure and their catalytic efficiency in water mediated Suzuki–Miyaura cross-coupling reaction
US20130137902A1 (en) Monophosphorus Ligands And Their Use In Cross-Coupling Reactions
CN105585593A (zh) 新型含吡啶基冠醚的手性双磷配体及其在不对称催化反应中的应用
WO2017193288A1 (fr) Synthèse de ligands de phosphine portant une liaison réglable : procédés pour leur utilisation dans une catalyse
CA2556850A1 (fr) Complexes de metaux de transition et de carbenes n-heterocycliques, methode de preparation connexe et utilisation desdits complexes dans des relations chimiques organiques catalyses par des metaux de transition
Yu et al. Unsymmetric-1, 3-disubstituted imidazolium salt for palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of aryl bromides
CN111217809B (zh) 一类手性含氮双烯配体及其制备方法和应用
EP0732337B1 (fr) Diphosphines asymmétriques optiquement actives et procédé pour préparer des substances optiquement actives en leur présence
CN112675920B (zh) 一类单手性中心催化剂及其制备和催化合成手性醇类化合物和手性α-烯丙醇的方法
JP4360096B2 (ja) 光学活性四級アンモニウム塩、その製造方法、及びこれを相間移動触媒として用いた光学活性α−アミノ酸誘導体の製造方法
CA2551412A1 (fr) Complexes de metaux de transition et de carbenes n-heterocycliques, methode de preparation connexe et utilisation desdits complexes dans des relations chimiques organiques catalyses par des metaux de transition
EP3303296A1 (fr) Ligands de benzo[h]quinoléine et complexes de ceux-ci
CN110627831A (zh) 二联芳缩醛膦、它们的制备方法及在偶联反应中的用途
EP3303353B1 (fr) Procédé
CN113999207B (zh) 含吡啶基手性nnn三齿配体、其不对称催化氢化合成及在不对称催化反应中的应用
CN112759616B (zh) 三碟烯卡宾钯化合物及其应用
KR102066464B1 (ko) 알킨의 헤테로아렌과의 카르보닐화를 위한 마르코브니코프-선택적 팔라듐 촉매
KR102051920B1 (ko) 다이이민-전이금속 착화합물을 포함하는 탄소-수소 아릴화 반응 또는 탄소-탄소 짝지음 반응용 촉매
CN106866736A (zh) 一种中心手性-轴手性缺电子双膦配体及其合成和应用
CN117143158A (zh) 一种环钯催化剂前体、环钯催化剂及制备方法和应用

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

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

Ref document number: 16901243

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 16901243

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载