EP4081343A2 - Ruthenium complex and method of conducting olefin metathesis reactions with formation of an internal bond using the ruthenium complex as a catalyst - Google Patents

Ruthenium complex and method of conducting olefin metathesis reactions with formation of an internal bond using the ruthenium complex as a catalyst

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Publication number
EP4081343A2
EP4081343A2 EP20845698.8A EP20845698A EP4081343A2 EP 4081343 A2 EP4081343 A2 EP 4081343A2 EP 20845698 A EP20845698 A EP 20845698A EP 4081343 A2 EP4081343 A2 EP 4081343A2
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European Patent Office
Prior art keywords
alkyl
denotes
aryl
perhaloalkyl
cycloalkyl
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EP20845698.8A
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German (de)
French (fr)
Inventor
Michal CHWALBA
Anna GAWIN
Krzysztof Skowerski
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Apeiron Synthesis Sp zoo
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Apeiron Synthesis Sp zoo
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Publication of EP4081343A2 publication Critical patent/EP4081343A2/en
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    • 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
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • 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
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2269—Heterocyclic carbenes
    • B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
    • 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
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2278—Complexes comprising two carbene ligands differing from each other, e.g. Grubbs second generation catalysts
    • 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
    • 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
    • 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
    • B01J2231/50—Redistribution or isomerisation reactions of C-C, C=C or C-C triple bonds
    • B01J2231/54—Metathesis reactions, e.g. olefin metathesis
    • B01J2231/543—Metathesis reactions, e.g. olefin metathesis alkene metathesis
    • 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

Definitions

  • the invention finds application in organic synthesis in its broad sense.
  • the (pre)catalysts most widely described in the literature are complexes of the Grubbs type (Gru), Hoveyda type (Hov), indenylidene, and recently Bertrand type catalysts having carbene cycloalkylamine ligand (CAAC) [ Grubbs etal. Chem. Rev. 2010, 110, 1746-1787; Nolan etal. Chem. Commun. 2014, 50, 10355-10375 ].
  • most of the olefin metathesis catalyst structures are derived from the above-mentioned ruthenium complexes.
  • Gre-II in this process made it possible to significantly reduce the amount of catalyst used, as well as the solvent volume, compared to the process conditions wherein Hov-I catalyst was used.
  • Hov-II-12 catalyst having iodide ligands is known in the art [ Wappel , Urbina-Bianco, C.A., Abbas, M, Albering, J.H., Saf, R, Nolan, S.P., Slugovc, C. Beilstein ./. Org. Chem. 2010, 6, 1091-1098 ].
  • the use of this compound was presented on the example of ring closing metathesis (RCM) and cross-metathesis (CM) reactions.
  • Catalysts bearing iodide ligands have greater steric hindrance, they are latent catalysts, which allowed to effectively use them in polymerization reactions of the ROMP type (they were activated at a temperature of at least 85°C).
  • the present invention relates to a ruthenium complex of general formula (1) wherein
  • R 1 denotes: hydrogen atom; halogen atom; C 1 -C 25 alkyl; C 1 -C 25 perhaloalkyl; C 3 -C 7 cycloalkyl; C 1 -C 25 alkoxy; C 5 -C 24 aryl; C 7 -C 24 aralkyl; C 5 -C 25 heteroaryl; 3-12 membered heterocycle, wherein the alkyl groups may be attached to each other to form a ring; or a group -OR’, -SR’, -NO 2 , -CN, -CONR’R”, -COOR’, -SO 2 R' -SO 2 NR'R", - COR’, in which the groups R’ and R”, each independently, denote C 1 -C 25 alkyl, C 1 -C 25 perhaloalkyl, C 5 -C 24 aryl, C 5 -C 25 heteroaryl or C 5 -C 24 perhaloaryl;
  • R 2 denotes C 1 -C 25 alkyl; C 1 -C 25 perhaloalkyl; C3-C7 cycloalkyl; C 1 -C 25 alkoxy; C 5 -C 24 aryl; a group -R’CONR"OR’, -CONR'R", -COOR’, -SO 2 R' -SO 2 NR’R”, -COR’, in which the groups R’ and R” each independently, denote C 1 -C 25 alkyl, C 1 -C 25 perhaloalkyl, C 5 -C 24 aryl, C 5 -C 25 heteroaryl or C 5 -C 24 perhaloaryl;
  • L denotes a neutral ligand in form of a P(R’) 3 group, wherein each R’ independently denotes C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 5 -C 24 aryl, C 7 -C 24 aralkyl, C 5 -C 24 perhaloaryl, or two R’ are linked together to form a cycloalkyl ring containing a ring phosphorus atom; or L denotes an L -heterocyclic carbene ligand of formula (2a) or (2b): in which: each R 3 and R 4 independently denotes C 1 -C 12 alkyl, C 3 -C 12 cycloalkyl, C 5 -C 20 aryl or C 5 -C 20 heteroaryl, which is optionally substituted with at least one C 1 -C 12 alkyl, C 1 -C 12 perhaloalkyl, C 2 -C 12 alkoxy or a halogen
  • the ruthenium complex according to the invention is selected from the following compounds:
  • the ruthenium complex is used selected from the compounds of the formulae 1-12, 2-12, 3-12, 4-12, 5-12 and 6-12 given above.
  • the reaction is carried out in an organic solvent, preferably selected from toluene, benzene, mesityl ene, di chi orom ethane, ethyl acetate, methyl acetate, tert-butyl methyl ether and cyclopentyl methyl ether.
  • organic solvent preferably selected from toluene, benzene, mesityl ene, di chi orom ethane, ethyl acetate, methyl acetate, tert-butyl methyl ether and cyclopentyl methyl ether.
  • reaction is carried out in the absence of a solvent.
  • the reaction is carried out at a temperature of 0 to 150°C, in particular 20 to 120°C.
  • the reaction time ranges from 1 minute to 24 hours.
  • the compound of formula (1) is added to the reaction mixture in a solid form.
  • the compound of formula (1) is added to the reaction mixture in form of a solution in an organic solvent.
  • the solution of the compound of formula (1) in an organic solvent is added to the reaction mixture by an infusion pump.
  • the method of the invention comprises conducting a metathesis reaction selected from ring closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM).
  • a metathesis reaction selected from ring closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM).
  • Ring-closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM) were particularly highly selective. It was also noted that adding the catalyst according to the invention by an infusion pump allowed to obtain a higher selectivity than adding it portion-wise.
  • carbene as used herein means a particle containing a neutral carbon atom with a valence of two and having two unpaired valence electrons.
  • carrier also includes carbene analogs in which the carbon atom is replaced with another chemical element such as boron, silicon, germanium, tin, lead, nitrogen, phosphorus, sulfur, selenium, tellurium.
  • halogen atom denotes an atom of an element selected from F, Cl, Br, I.
  • alkyl refers to a saturated, linear or branched hydrocarbon substituent with the indicated number of carbon atoms.
  • alkyl substituents are -methyl, -ethyl, -n- propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl, -n-nonyl, and -n-decyl.
  • Representative branched -(C 1 -C 10 )-alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, - neopentyl, -1-methylbutyl, -2-methylbutyl, -3-methylbutyl, -1,1-dimethylpropyl, -1,2- dimethylpropyl, -1-methylpentyl, -2-methylpentyl, -3-methylpentyl, -4-methylpentyl, -1- ethylbutyl, -2-ethylbutyl, -3-ethylbutyl, -1, 1-dimethylbutyl, -1,2-dimethylobutyI, -1,3- dimethylbutyl, -2,2-dimethylbutyl, -2,3-dimethylbutyl, -3, 3 -dimethyl
  • alkoxy refers to an alkyl substituent as defined above attached through an oxygen atom.
  • perhaloalkyl denotes an alkyl group as defined above in which all the hydrogen atoms have been replaced with the same or different halogen atoms.
  • cycloalkyl refers to a saturated mono- or polycyclic hydrocarbon substituent having
  • cycloalkyl substituents are -cyclopropyl, -cyclobutyl, - cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, -cyclodecyl.
  • alkenyl refers to a saturated, linear or branched non-cyclic hydrocarbon substituent comprising 2-25 carbon atoms and containing at least one carbon-carbon double bond.
  • alkenyl substituents are -vinyl, -allyl, -1-butenyl, -2-butenyl, -isobutylenyl, -1- pentenyl, -2-pentenyl, -3 -methyl- 1-butenyl, -2-methyl-2-butenyl , -2,3-dimethyl-2-butenyl, -1- hexenyl, -2-hexenyl, -3-hexenyl, -1-heptenyl, -2-heptenyl, -3-heptenyl, - 1-octenyl , -2-octenyl, -3-octenyl, -1-nonenyl, -2-nonenyl, -3-
  • aryl refers to an aromatic mono- or polycyclic hydrocarbon substituent having 5-24 carbon atoms.
  • aryl substituents are -phenyl, -tolyl, -xylyl, -naphthyl, -2,4,6- trimethylphenyl, -2 -fluorophenyl, -4-fluorophenyl, -2,4,6-trifluorophenyl, -2,6-difluorophenyl, -4-nitrophenyl.
  • aralkyl refers to an alkyl substituent as defined above substituted with at least one aryl as defined above. Examples of the aralkyl substituent are -benzyl, -diphenylmethyl, - triphenylmethyl and the like.
  • heteroaryl refers to an aromatic, mono- or polycyclic hydrocarbon substituent, having 5-25 carbon atoms, wherein at least one carbon atom has been replaced with a heteroatom selected from O, N and S.
  • heteroaryl substituents are -furyl, - thienyl, -imidazolyl, -oxazolyl, -thiazolyl, -isoxazolyl, -triazolyl, -oxadiazolyl, -thiadiazolyl, - tetrazolyl, -pyridyl, -pyrimidyl, -triazinyl, -indolyl, -benzo [b] furyl, -benzo [b] thienyl, - indazolyl, -benzoimidazolyl, -azaindolyl, -quinolyl, -isoquinolyl, -carbazolyl.
  • heterocycle refers to a saturated or partially unsaturated, mono- or polycyclic hydrocarbon substituent having 3-12 carbon atoms, wherein at least one carbon atom has been replaced by a heteroatom selected from O, N and S.
  • heterocyclic substituents are furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pyrrolidinonyl, pyrrolidinyl, hydantoinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, indurinyl, chinolinyl, chrominyl, chinolinyl, chrominyl, furanyl, benzo [b] thiophenyl, indazolyl, purinyl, 4H-quinolys
  • neutral ligand refers to an uncharged substituent capable of coordination with a metallic center (ruthenium atom).
  • ligands are: amines, phosphines and their oxides, orthophosphates (III) and alkyl and aryl phosphates, arsines and their oxides, ethers, alkyl and aryl sulfides, coordinated hydrocarbons, alkyl and aryl halides.
  • anionic ligand refers to a substituent capable of coordination with a metallic center (ruthenium atom) having a charge capable of partially or fully compensating for the charge of the metallic center.
  • ligands are fluoride, chloride, bromide, iodide, cyanide, cyanate and thiocyanate anions, carboxylic acid anions, alcohol anions, phenol anions, thiol and thiophenol anions, delocalized hydrocarbon anions (e.g.
  • organo(sulfuric) acid anions and (organo)phosphorus acid anions as well as esters thereof such as, for example, anions of alkylsulfonic and arylsulfonic acids, anions of alkylphosphoric and arylphosphoric acids, anions of alkyl and aryl esters of sulfuric acid, anions of alkyl and aryl esters of phosphoric acids, anions of alkyl and aryl esters of alkylphosphoric and arylphosphoric acids.
  • the anionic ligand may have neutral groups linked thereto, such as a catechol anion, an acetylacetone anion, and a salicylaldehyde anion.
  • Anionic ligands and neutral ligands may be linked together to form multidentate ligands, for example bidentate ligand, tridentate ligand, tetradentate ligand.
  • multidentate ligands for example bidentate ligand, tridentate ligand, tetradentate ligand.
  • examples of such ligands are: catechol anion, acetylacetone anion and salicylaldehyde anion.
  • heteroatom denotes an atom selected from the group comprising oxygen, sulfur, nitrogen, phosphorus and others.
  • Substrates benzyl(allyl)hex-5-en-2-ynyl carbamate (S1), hexenol acetate (S2b), ethyl undecenoate (S2b) and 9-decenoic acid methyl ester (S3) are commercially available compounds.
  • S1 and S2b were distilled under reduced pressure and stored over activated alumina. All reactions were carried out under argon atmosphere. Toluene was washed with citric acid, water, dried with 4 ⁇ molecular sieves and deoxygenated with argon.
  • composition of the reaction mixtures was determined by gas chromatography using a PerkinElmer Clarus 680 GC apparatus equipped with a GL Sciences InertCap® 5MS / NP capillary column. Individual components of the reaction mixtures were identified by comparing the retention times to commercial standards or those isolated from reaction mixtures for which the structure was confirmed by NMR.
  • Example 1
  • Table 1 Comparison of conversion degree when using iodide and chloride complexes (1 and 2) in the RCM reaction of the S1 substrate.
  • Table 2. Comparison of conversion degree when using iodide and chloride 3-6 complexes in the RCM reaction of the S1 substrate.
  • CM reaction was performed using only iodide complexes, which were added to the mixture by an infusion pump at a dropping rate of 20 ⁇ L/min.
  • the project is co-fmanced by the European Union from the European Regional Development Fund under the Intelligent Development Operational Program 2014-2020, on the basis of the co-financing agreement No. POIR.01.01.01-00-1186 / 15-00.

Abstract

The invention relates to a ruthenium complex of general formula (1) wherein R1, R2 and L are as defined in the description. Furthermore, the invention relates to a method for conducting an olefin metathesis reaction to form an internal C=C bond using the ruthenium complex of general formula (1) as a catalyst.

Description

RUTHENIUM COMPLEX AND METHOD OF CONDUCTING OLEFIN METATHESIS REACTIONS WITH FORMATION OF AN INTERNAL BOND USING THE RUTHENIUM COMPLEX AS A CATALYST
The invention relates to a ruthenium complex of formula (I) as defined below and a method for conducting olefin metathesis reaction to form an internal C=C bond using this ruthenium complex as a catalyst. The invention finds application in organic synthesis in its broad sense.
In recent years, great progress has been made in the application of olefin metathesis in organic synthesis [R. H. Grubbs (Editor), A.G. Wenzel (Editor), DJ O'Leary (Editor), E. Khosravi (Editor), Handbook of Olefin Metathesis, 2nd Edition, 3rd Volumes 2015, John Wiley & Sons, Inc., 1,608 pages]. Many catalysts are known in the art which have both high activity in various types of metathesis reactions and a high functional group tolerance. Due to the combination of these features, metathesis catalysts are essential in modern organic synthesis and industry. The (pre)catalysts most widely described in the literature are complexes of the Grubbs type (Gru), Hoveyda type (Hov), indenylidene, and recently Bertrand type catalysts having carbene cycloalkylamine ligand (CAAC) [ Grubbs etal. Chem. Rev. 2010, 110, 1746-1787; Nolan etal. Chem. Commun. 2014, 50, 10355-10375 ]. In the remaining cases, most of the olefin metathesis catalyst structures are derived from the above-mentioned ruthenium complexes.
From the point of view of industrial applications, there is a need for catalysts with a very high durability and resistance to contamination. Additionally, it is desirable to use as little catalyst as possible to reduce costs and formed by-products. There are many examples of industrial applications of ruthenium complexes where process optimization leading to a reduction in the amount of catalyst was essential. A representative example is the use of Gre-II catalyst in a macrocyclization reaction [Farina, V, Shu, C., Zeng, X., Wei, X, Han, Z., Yee, N. K., Senanayake, C. H., Org. Process Res. Dev., 2009, 13, 250-254 ]. The use of Gre-II in this process made it possible to significantly reduce the amount of catalyst used, as well as the solvent volume, compared to the process conditions wherein Hov-I catalyst was used. Hov-II-12 catalyst having iodide ligands is known in the art [ Wappel , Urbina-Bianco, C.A., Abbas, M, Albering, J.H., Saf, R, Nolan, S.P., Slugovc, C. Beilstein ./. Org. Chem. 2010, 6, 1091-1098 ]. The use of this compound was presented on the example of ring closing metathesis (RCM) and cross-metathesis (CM) reactions. In each of the examples disclosed in the publication, the efficiency of the iodide (pre)catalyst was comparable to that of its dichloride analogue. The amount of catalyst used was about 1-5 mol%. Furthermore, the selectivity of this compound for the formation of C=C double bonds has not been described.
Another use of Hoveyda-type iodide complexes in metathesis reactions was disclosed in a publication of Tracz, A., Matczak, M, Urbaniak, K., Skowerski, K. Beilstein ./. Org. Chem.
2015, 11, 1823-1832.
This publication proved the effect of iodide (pre)catalysts on the selectivity of C=C double bond formation. It was found that the use of the complex with iodide ligands allows to significantly increase the metathesis reaction selectivity. The amount of the catalyst used in the CM reactions was about 0.4-0.5 mol%, while in simple RCM reactions it was over 0.0025 mol%.
In the scientific publication from 2001 [M. S. Sanford etal, J. Am. Chem. Soc. 2001, 123, 6543- 6554\ the research on the mechanism of metathesis reactions and the activity of ruthenium catalysts in olefin metathesis was described, said research being focused on Gru-I and Gru-II complexes. In this publication, on pages 6550-6551, the general observation is presented that an increase of anionic ligand radius in the series of halides (chloride anion, bromide anion, iodide anion) is associated with an increase in the steric hindrance at the ruthenium atom. In this series, an increased rate of the catalyst initiation stage at the phosphine dissociation stage was observed (Grubbs complexes are 16 electron complexes, while the active catalyst are 14 electron complexes formed after the dissociation of the ligand chelating the ruthenium atom). Interestingly, the rapid initiation of di-iodide complexes results in a merely moderate catalytic activity and low efficiency of metathesis processes.
In the scientific publication from 2010 [R. 77. Grubbs et al., Organometallics 2011, 30, 6713- 6717] Hovey da-type ruthenium complexes were presented containing asymmetric NHC ligands with modified anionic ligands. These catalysts were inactive at room temperature. Complexes containing chloride anions were promoting RCM and CM reactions, but unfortunately this catalyst requires high process temperature (above 85°C), which resulted in the formation of significant amounts of C=C double bond migration products in the reaction mixture. In order to inhibit the isomerization of the C=C double bond, iodide analogs were obtained. Catalysts bearing iodide ligands have greater steric hindrance, they are latent catalysts, which allowed to effectively use them in polymerization reactions of the ROMP type (they were activated at a temperature of at least 85°C).
The scientific publication from 2001 [R. C. Hughes et al., J. Org. Chem. 2001, 66, 5545-5551] discloses an alternative method of continuously feeding the reaction mixture with the ruthenium olefin metathesis catalyst in the form of a solution via an infusion pump.
The aim of the present invention was to develop a new olefin metathesis catalysts for C=C internal bond formation, showing high activity while maintaining high selectivity.
The present invention relates to a ruthenium complex of general formula (1) wherein
R1 denotes: hydrogen atom; halogen atom; C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; C7-C24 aralkyl; C5-C25 heteroaryl; 3-12 membered heterocycle, wherein the alkyl groups may be attached to each other to form a ring; or a group -OR’, -SR’, -NO2, -CN, -CONR’R”, -COOR’, -SO2R' -SO2NR'R", - COR’, in which the groups R’ and R”, each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
R2 denotes C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; a group -R’CONR"OR’, -CONR'R", -COOR’, -SO2R' -SO2NR’R”, -COR’, in which the groups R’ and R” each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
L denotes a neutral ligand in form of a P(R’)3 group, wherein each R’ independently denotes C1-C6 alkyl, C3-C8 cycloalkyl, C5-C24 aryl, C7-C24 aralkyl, C5-C24 perhaloaryl, or two R’ are linked together to form a cycloalkyl ring containing a ring phosphorus atom; or L denotes an L -heterocyclic carbene ligand of formula (2a) or (2b): in which: each R3 and R4 independently denotes C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C2-C12 alkoxy or a halogen atom; each R5, R6, R7, R8, R9, R10 independently denotes a hydrogen atom, C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C1-C12 alkoxy or a halogen atom, or the groups R5, R6, R7, R8, R9, R10 are linked together to form a C4-C10 cyclic or C4-C12 polycyclic system; with the exception of compounds, in which simultaneously R1 denotes -NO2, R2 denotes isopropyl and L denotes
Preferably, the ruthenium complex according to the invention is selected from the following compounds:
The invention also relates to a method of conducting an olefin metathesis reaction with the formation of an internal C=C bond using a ruthenium complex as a catalyst, wherein the ruthenium complex of the general formula (1) as defined above is used in an amount not greater than 50 ppm.
Preferably, in the method according to the invention the ruthenium complex is used selected from the compounds of the formulae 1-12, 2-12, 3-12, 4-12, 5-12 and 6-12 given above.
Preferably, in the method according to the invention, the reaction is carried out in an organic solvent, preferably selected from toluene, benzene, mesityl ene, di chi orom ethane, ethyl acetate, methyl acetate, tert-butyl methyl ether and cyclopentyl methyl ether.
In another preferred embodiment of the method according to the invention, the reaction is carried out in the absence of a solvent.
Preferably, in the method according to the invention, the reaction is carried out at a temperature of 0 to 150°C, in particular 20 to 120°C.
Preferably, in the method according to the invention, the reaction time ranges from 1 minute to 24 hours.
Preferably, in the method according to the invention, the compound of formula (1) is added to the reaction mixture in a solid form. In another preferred embodiment of the method according to the invention, the compound of formula (1) is added to the reaction mixture in form of a solution in an organic solvent. In a particularly preferred embodiment, the solution of the compound of formula (1) in an organic solvent is added to the reaction mixture by an infusion pump.
Preferably, the method of the invention comprises conducting a metathesis reaction selected from ring closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM).
As a result of the research carried out by the Inventors, it turned out that the use of compounds of general formula (1) having anionic iodide ligands allows to carry out the metathesis reaction with the formation of an internal C=C bond using a catalyst in the amount below 50 ppm, i.e. much lower than in the previous reports while maintaining high selectivity. The results of experimental work showed that the catalysts with iodide ligands are characterized by very high stability and resistance to the presence of various functional groups. Moreover, these compounds proved to be resistant to contaminants in solvents. Due to these properties, it is possible to carry out the metathesis reaction with a very small amount of catalyst. Ring-closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM) were particularly highly selective. It was also noted that adding the catalyst according to the invention by an infusion pump allowed to obtain a higher selectivity than adding it portion-wise.
In this description, the terms used have the following meanings. Undefined terms herein have meanings that are given and understood by one of ordinary skill in the art in view of his/her best knowledge, the present disclosure, and the context of the description. Unless otherwise stated, the following chemical term conventions are used in this specification with the meanings indicated as in the definitions below:
The term "carbene" as used herein means a particle containing a neutral carbon atom with a valence of two and having two unpaired valence electrons. The term "carbene" also includes carbene analogs in which the carbon atom is replaced with another chemical element such as boron, silicon, germanium, tin, lead, nitrogen, phosphorus, sulfur, selenium, tellurium.
The term " halogen atom " denotes an atom of an element selected from F, Cl, Br, I.
The term "alkyl" refers to a saturated, linear or branched hydrocarbon substituent with the indicated number of carbon atoms. Examples of alkyl substituents are -methyl, -ethyl, -n- propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl, -n-nonyl, and -n-decyl. Representative branched -(C1-C10)-alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, - neopentyl, -1-methylbutyl, -2-methylbutyl, -3-methylbutyl, -1,1-dimethylpropyl, -1,2- dimethylpropyl, -1-methylpentyl, -2-methylpentyl, -3-methylpentyl, -4-methylpentyl, -1- ethylbutyl, -2-ethylbutyl, -3-ethylbutyl, -1, 1-dimethylbutyl, -1,2-dimethylobutyI, -1,3- dimethylbutyl, -2,2-dimethylbutyl, -2,3-dimethylbutyl, -3, 3 -dimethyl-butyl, -1-methylhexyl, -
2-methylhexyl , -3-methylhexyl, -4-methylhexyl, -5-methylhexyl, -1,2-dimethylpentyl, -1,3- dimethylpentyl, -1,2-dimethylhexyl, -1,3-dimethylhexyl, -3, 3-dimethylhexyl, -1,2- dimethylheptyl, -1,3-dimethylheptyl, and -3,3-dimethylheptyl.
The term " alkoxy " refers to an alkyl substituent as defined above attached through an oxygen atom.
The term "perhaloalkyl" denotes an alkyl group as defined above in which all the hydrogen atoms have been replaced with the same or different halogen atoms.
The term "cycloalkyl" refers to a saturated mono- or polycyclic hydrocarbon substituent having
3-7 carbon atoms. Examples of cycloalkyl substituents are -cyclopropyl, -cyclobutyl, - cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, -cyclodecyl.
The term " alkenyl " refers to a saturated, linear or branched non-cyclic hydrocarbon substituent comprising 2-25 carbon atoms and containing at least one carbon-carbon double bond. Examples of alkenyl substituents are -vinyl, -allyl, -1-butenyl, -2-butenyl, -isobutylenyl, -1- pentenyl, -2-pentenyl, -3 -methyl- 1-butenyl, -2-methyl-2-butenyl , -2,3-dimethyl-2-butenyl, -1- hexenyl, -2-hexenyl, -3-hexenyl, -1-heptenyl, -2-heptenyl, -3-heptenyl, - 1-octenyl , -2-octenyl, -3-octenyl, -1-nonenyl, -2-nonenyl, -3-nonenyl, -1-decenyl, -2-decenyl, -3-decenyl.
The term "aryl" refers to an aromatic mono- or polycyclic hydrocarbon substituent having 5-24 carbon atoms. Examples of aryl substituents are -phenyl, -tolyl, -xylyl, -naphthyl, -2,4,6- trimethylphenyl, -2 -fluorophenyl, -4-fluorophenyl, -2,4,6-trifluorophenyl, -2,6-difluorophenyl, -4-nitrophenyl.
The term "aralkyl" refers to an alkyl substituent as defined above substituted with at least one aryl as defined above. Examples of the aralkyl substituent are -benzyl, -diphenylmethyl, - triphenylmethyl and the like.
The term " heteroaryl " refers to an aromatic, mono- or polycyclic hydrocarbon substituent, having 5-25 carbon atoms, wherein at least one carbon atom has been replaced with a heteroatom selected from O, N and S. Examples of heteroaryl substituents are -furyl, - thienyl, -imidazolyl, -oxazolyl, -thiazolyl, -isoxazolyl, -triazolyl, -oxadiazolyl, -thiadiazolyl, - tetrazolyl, -pyridyl, -pyrimidyl, -triazinyl, -indolyl, -benzo [b] furyl, -benzo [b] thienyl, - indazolyl, -benzoimidazolyl, -azaindolyl, -quinolyl, -isoquinolyl, -carbazolyl. The term " heterocycle " refers to a saturated or partially unsaturated, mono- or polycyclic hydrocarbon substituent having 3-12 carbon atoms, wherein at least one carbon atom has been replaced by a heteroatom selected from O, N and S. Examples of heterocyclic substituents are furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pyrrolidinonyl, pyrrolidinyl, hydantoinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, indurinyl, chinolinyl, chrominyl, chinolinyl, chrominyl, furanyl, benzo [b] thiophenyl, indazolyl, purinyl, 4H-quinolysinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, carbazolyl, b-carbolinyl.
The term "neutral ligand " refers to an uncharged substituent capable of coordination with a metallic center (ruthenium atom). Examples of such ligands are: amines, phosphines and their oxides, orthophosphates (III) and alkyl and aryl phosphates, arsines and their oxides, ethers, alkyl and aryl sulfides, coordinated hydrocarbons, alkyl and aryl halides.
The term "anionic ligand " refers to a substituent capable of coordination with a metallic center (ruthenium atom) having a charge capable of partially or fully compensating for the charge of the metallic center. Examples of such ligands are fluoride, chloride, bromide, iodide, cyanide, cyanate and thiocyanate anions, carboxylic acid anions, alcohol anions, phenol anions, thiol and thiophenol anions, delocalized hydrocarbon anions (e.g. cyclopentadiene), organo(sulfuric) acid anions and (organo)phosphorus acid anions as well as esters thereof (such as, for example, anions of alkylsulfonic and arylsulfonic acids, anions of alkylphosphoric and arylphosphoric acids, anions of alkyl and aryl esters of sulfuric acid, anions of alkyl and aryl esters of phosphoric acids, anions of alkyl and aryl esters of alkylphosphoric and arylphosphoric acids). Optionally, the anionic ligand may have neutral groups linked thereto, such as a catechol anion, an acetylacetone anion, and a salicylaldehyde anion. Anionic ligands and neutral ligands may be linked together to form multidentate ligands, for example bidentate ligand, tridentate ligand, tetradentate ligand. Examples of such ligands are: catechol anion, acetylacetone anion and salicylaldehyde anion.
The term " heteroatom " denotes an atom selected from the group comprising oxygen, sulfur, nitrogen, phosphorus and others.
Exemplary embodiments of the invention
The following examples are provided merely to illustrate the invention and to explain its various aspects, not to be limiting, and should not be construed with its entire scope as defined in the appended claims. In the following examples, unless otherwise indicated, standard materials and methods used in the art were used or the recommendations of the manufacturers were followed for specific reagents and methods.
The performance of the (pre)catalysts of the general formula 1 according to the invention was compared with that of the (pre)catalysts, the structures of which are illustrated below:
Substrates: benzyl(allyl)hex-5-en-2-ynyl carbamate (S1), hexenol acetate (S2b), ethyl undecenoate (S2b) and 9-decenoic acid methyl ester (S3) are commercially available compounds. S1 and S2b were distilled under reduced pressure and stored over activated alumina. All reactions were carried out under argon atmosphere. Toluene was washed with citric acid, water, dried with 4Ά molecular sieves and deoxygenated with argon.
Composition of the reaction mixtures was determined by gas chromatography using a PerkinElmer Clarus 680 GC apparatus equipped with a GL Sciences InertCap® 5MS / NP capillary column. Individual components of the reaction mixtures were identified by comparing the retention times to commercial standards or those isolated from reaction mixtures for which the structure was confirmed by NMR. Example 1
Reaction of exchanging a chloride ligand with an iodide one
The respective chloride complex (102 - 602) (1 equivalent) was dissolved in methanol (C = 0.1 M) and an aliquot of KI (30 equivalents) was added. The mixture was stirred for 12 hours. The precipitate was then filtered off, the solution was evaporated and then dissolved in methylene chloride and filtered through a thin layer of silica gel. The filtrate was concentrated and a new portion of methanol and KI was added. The procedure was repeated three times. In the last step, the obtained complex was crystallized from a solvent mixture of methylene chi ori de-methanol .
112: 1H NMR (500 MHz, CD2C12) δ 15.41 - 15.17 (m, 1H), 8.87 - 8.78 (dt, J = 6.6, 1.4 Hz, 1H), 8, 54 - 8.47 (dd, J = 9.2, 2.7 Hz, 1H), 7.82 - 7.71 (m, 2H), 7.64 - 7.51 (m, 2H), 7, 43 - 7.30 (m, 4H), 7.08 - 6.99 (d, J = 9.1 Hz, 1H), 5.22 - 5.08 (hept, J = 6.2 Hz, 1H) , 4.54 - 4.22 (m, 2H), 4.20 - 3.92 (m, 2H), 2.57 - 2.49 (d, J = 18.7 Hz, 6H), 1.66 - 1.60 (d, J = 6.1 Hz, 3H), 1.54 - 1.48 (m, 3H).
212: 1H NMR (500 MHz, CD2C12) δ 15.59 - 15.17 (m, 1H), 8.53 - 8.44 (dd, J = 9.1, 2.7 Hz, 1H), 7, 88 - 7.77 (m, 1H), 7.70 - 7.57 (t, J = 7.9 Hz, 1H), 7.49 - 7.17 (m, 5H), 6.98 - 6, 93 (d, J = 9.1 Hz, 1H), 5.17 - 4.98 (dt, J = 12.3, 6.2 Hz, 1H), 4.35 - 4.09 (d, J = 1.7 Hz, 4H), 3.17 - 2.76 (m, 6H), 1.75 - 0.93 (m, 20H).
312: 1H NMR (500 MHz, C6D6) δ 16.72 - 16.42 (d, J = 0.9 Hz, 1H), 7.25 - 7.20 (dd, J = 7.5, 1.6 Hz, 1H), 7.15 - 7.10 (d, J = 1.6 Hz, 1H), 7.05 - 7.00 (d, J = 2.1 Hz, 1H), 6.95 - 6 , 90 (m, 1H), 6.91 - 6.87 (d, J = 2.1 Hz, 1H), 6.87 - 6.83 (m, 1H), 6.72 - 6.66 (td , J = 7.4, 0.8 Hz, 1H), 6.64
- 6.59 (d, J = 8.2 Hz, 1H), 5.21 - 5.11 (d, J = 7.8 Hz, 1H), 3.95 - 3.84 (q, J = 7.1 Hz, 1H), 3.74
- 3.62 (dt, J = 12.0, 9.4 Hz, 1H), 3 , 59 - 3.47 (ddd, J = 10.9, 9.4, 5.6 Hz, 1H), 3.44 - 3.36 (dt, J = 11.2, 9.6 Hz, 1H) , 3.29 - 3.19 (m, 6H), 2.97 - 2.87 (s, 3H), 2.82 - 2.75 (s, 3H), 2.63 - 2.60 (s, 3H), 2.49 - 2.46 (s, 3H), 2.27 - 2.24 (s, 3H), 2.21 - 2.18 (s, 3H), 0.94 - 0.91 ( s, 1H), 0.90 - 0.85 (d, J = 6.9 Hz, 3H), 0.83 - 0.77 (d, J = 6.9 Hz, 3H).
412: 1HNMR (500 MHz, C6D6) δ 16.80 - 16.50 (s, 1H), 7.47 - 7.39 (dd, J = 14.9, 7.3 Hz, 2H), 7, 37 - 7.27 (m, 4H), 6.70 - 6.52 (m, 2H), 5.21 - 4.89 (m, 2H), 4.55 - 4.22 (m, 2H), 3.94 - 3.51 (m, 5H), 3.20 - 3.11 (s, 3H), 2.65 - 2.56 (s, 3H), 1.97 - 1.68 (m, 6H ), 1.69 - 1.46 (m, 4H), 1.39
- 1.13 (m, 15H), 0.94 - 0.80 (m, 6H).
512: 1H NMR (500 MHz, C6D6) δ 16.63 - 16.40 (s, 1H), 7.53 - 7.24 (m, 7H), 7.11 - 7.04 (m, 1H), 6.65 - 6.59 (t, J = 7.5 Hz, 1H), 6.36 - 6.30 (d, J = 8.2 Hz, 1H), 5.18 - 5.05 (q, J = 6.5 Hz, 1H), 4.88 - 4.72 (p, J = 6.7 Hz, 1H), 4.46 - 4.30 (hept, J = 6.5 Hz, 1H), 4.28 - 4.10 (m, 1H), 3.85 - 3.69 (m, 4H), 2.98 - 2.89 (s, 3H), 2.67 - 2.59 (s, 3H), 1.89 - 1.72 (dd, J = 28.3, 6.4 Hz, 6H), 1.55 - 1.45 (m, 6H), 1.38 - 1.15 (m, 16H).
612: 1HNMR (500 MHz, C6D6) δ 16.46 - 16.30 (s, 1H), 8.05 - 7.98 (d, J = 2.7 Hz, 1H), 7.93 - 7, 85 (dd, J = 9.1, 2.7 Hz, 1H), 7.47 - 7.22 (m, 7H), 5.97 - 5.90 (d, J = 8.9 Hz, 1H) , 5.12 - 4.96
(q, J = 6.3 Hz, 1H), 4.78 - 4.63 (m, 1H), 4.28 - 4.06 (m, 2H), 3.88 - 3.58 (m, 5H), 3.09 - 2.92 (s, 3H), 2.66 - 2.55 (s, 3H), 1.86 - 1.68 (dd, J = 28, 6, 6.2Hz, 6H), 1.56 - 1.50 (m, 2H), 1.42 - 1.36 (d, J = 6.6 Hz, 3H), 1.31 - 1.15 (m, 15H).
Example 2 RCM reaction of S1 substrate
The (pre)catalyst (0.044 μmol, 20 ppm) in toluene (20 μl) was added in one portion to a solution of S1 (0.6 g, 2.2 mmol) in toluene (11 ml) at 50°C. At the appropriate time intervals (given in Table 1 below), samples of the reaction mixture were taken, to which 3 drops of ethyl vinyl ether were added to deactivate the catalyst. Samples were analyzed by gas chromatography.
Table 1. Comparison of conversion degree when using iodide and chloride complexes (1 and 2) in the RCM reaction of the S1 substrate. Table 2. Comparison of conversion degree when using iodide and chloride 3-6 complexes in the RCM reaction of the S1 substrate.
In the RCM reaction of S1, the iodide catalysts 3 (90 min, 23% conv.) and 4 (90 min, 47% conv.) showed higher activity than their dichloride analogs 3 and 4: 90 min, 7% and 25% conv., respectively.
Example 3
CM reaction of hexenol acetate (S2a) with ethyl undecene (S2b)
The solution in toluene of the appropriate (pre)catalyst from the group of compounds of formulae 1-6 (5 ppm) was added portion-wise (20 μl) every 10 minutes to a solution of S2a (2 g, 14 mmol, 1 molar equivalent) and S2b (0.655 ml, 10.0 mmol, 1 molar equivalent) at 40°C under argon atmosphere. The mixture was stirred for 2 hours. Argon stream was passed through the solution during the reaction. Samples were taken, and to each sample 3 drops of ethyl vinyl ether were added to deactivate the catalyst. Samples were analyzed by gas chromatography (GC).
Along with P2d: isomer of P2a + P2e: isomer of P2b + P2f: isomer of P2c isomer of S2a + isomer of S2b isomer Table 3. Comparison of conversion degree when using iodide and chloride 1-2 complexes in the cross-metathesis reaction of S2a and S2b. The catalyst was added in 10 portions of 5 ppm. Table 4. Comparison of conversion degree when using iodide and chloride 3-6 complexes in the cross-metathesis reaction of S2a and S2b. The catalyst was added in 10 portions of 5 ppm.
By using iodide complexes having NHC ligands and nitro ligand, a higher content of expected product P2a was obtained in the reaction mixture than by using their chloride analogs. In the case of the complexes having a Weinreb amide ligand, only the 3-12, 5-12 and 6-12 complexes gave a higher P2a content.
In another experiment, the CM reaction was performed using only iodide complexes, which were added to the mixture by an infusion pump at a dropping rate of 20 μL/min.
Table 5. Comparison of conversion degree when using iodide complexes 3 and 4 in the cross-metathesis reaction of S2a and S2b. Catalyst added using an infusion pump. In the above experiment, all iodide complexes showed similar activity and selectivity. The addition of the catalyst by an infusion pump allowed to obtain a higher selectivity than adding portion-wise. The best result was obtained for the catalyst 4-12: product P2a = 28.97% and the smallest amount of isomers 0.8%. Example 4
Homometathesis reaction of 9-decenoic acid methyl ester (S3)
A solution of the appropriate (pre)catalyst (10 ppm) in toluene (20 μl) was added To S3 (1.00 g, 5.4 mmol) in three portions at 20 minute intervals, at 55°C under argon atmosphere. Argon stream was passed through the solution during the reaction. Samples were taken, and to each one 3 drops of ethyl vinyl ether were added to deactivate the catalyst. Samples were analyzed by gas chromatography.
Table 6. Comparison of activity of iodide and chloride 1-2 complexes in the homometathesis of S3 substrate.
Table 7. Comparison of activity of iodide and chloride 3-6 complexes in the homometathesis of S3 substrate.
In the 9-decenoic acid methyl ester homometathesis reaction, chloride complexes turned out to be more active - with the exception of iodide complexes having a ligand derived from Weinreb's amide (Table 7): 3-12 (K = 41%, S = 91%) and 5-12 ( K = 99%, S = 81%), while in each case higher selectivity was obtained with iodide complexes.
Example 5
Homometathesis reaction of 5-hexenol acetate (S2a)
A solution of the appropriate (pre)catalyst (20 ppm) in toluene (0.1 ml) was added in one portion to S2a (5.00 g, 35.2 mmol) at 60°C under argon. The mixture was stirred for 2 hours. Argon stream was passed through the solution during the reaction. Samples were taken and to each 3 drops of ethyl vinyl ether were added to deactivate the catalyst. Samples were analyzed by gas chromatography. Table 8. Comparison of activity of iodide and chloride complexes (1-2) in the homometathesis reaction of S2a substrate.
Table 9. Comparison of activity of iodide and chloride 3-6 complexes in the homometathesis reaction of S2a substrate. Based on the results presented in the Tables, it can be seen that all reactions carried out with the use of iodide complexes gave much higher selectivity and, in most cases, lower conversions than in the case of using chloride catalysts. The 5-12 catalyst allowed to obtain a conversion level similar to the chloride analog (5-12: K = 97%, 5-C12: K => 99%) and at the same time much higher selectivity (5-12: S = 91%, 5-C12: S = 57%), which is a great advantage especially in areas such as the pharmaceutical industry.
The project is co-fmanced by the European Union from the European Regional Development Fund under the Intelligent Development Operational Program 2014-2020, on the basis of the co-financing agreement No. POIR.01.01.01-00-1186 / 15-00.

Claims

Claims
1. A ruthenium complex of general formula (1) wherein
R1 denotes: hydrogen atom; halogen atom; C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; C7-C24 aralkyl; C5-C25 heteroaryl; 3-12 membered heterocycle, wherein the alkyl groups may be attached to each other to form a ring; or a group -OR’, -SR’, -NO2, -CN, -CONR’R”, -COOR’, -SO2R’, -SO2NR'R”, - COR’, in which the groups R’ and R”, each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
R2 denotes C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; a group -R’CONR’OR’, -CONR’R”, -COOR’, -SO2R’, -SO2NR’R”, -COR’, in which the groups R’ and R” each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
L denotes a neutral ligand in form of a P(R’)3 group, wherein each R’ independently denotes C1-C6 alkyl, C3-C8 cycloalkyl, C5-C24 aryl, C7-C24 aralkyl, C5-C24 perhaloaryl, or two R’ are linked together to form a cycloalkyl ring containing a ring phosphorus atom; or L denotes an N-heterocyclic carbene ligand of formula (2a) or (2b): in which: each R3 and R4 independently denotes C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C2-C12 alkoxy or a halogen atom; each R5, R6, R7, R8, R9, R10 independently denotes a hydrogen atom, C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C1-C12 alkoxy or a halogen atom, or the groups R5, R6, R7, R8, R9, R10 are linked together to form a C4-C10 cyclic or C4-C12 polycyclic system; with the exception of compounds, in which simultaneously R1 denotes -NO2, R2 denotes isopropyl and L denotes
2. The ruthenium complex according to claim 1, characterized in that it is selected from the following compounds:
3. A method of conducting olefin metathesis reaction with the formation of an internal bond using a ruthenium complex as a catalyst, characterized in that the ruthenium complex of the general formula (1) wherein
R1 denotes: hydrogen atom; halogen atom; C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; C7-C24 aralkyl; C5-C25 heteroaryl; 3-12 membered heterocycle, wherein the alkyl groups may be attached to each other to form a ring; or a group -OR’, -SR’, -NO2, -CN, -CONR’R”, -COOR’, -SO2R’, -SO2NR'R”, - COR’, in which the groups R’ and R”, each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
R2 denotes C1-C25 alkyl; C1-C25 perhaloalkyl; C3-C7 cycloalkyl; C1-C25 alkoxy; C5-C24 aryl; a group -R’CONR OR’, -CONR’R”, -COOR’, -SO2R’, -SO2NR’R”, -COR’, in which the groups R’ and R” each independently, denote C1-C25 alkyl, C1-C25 perhaloalkyl, C5-C24 aryl, C5-C25 heteroaryl or C5-C24 perhaloaryl;
L denotes a neutral ligand in form of a P(R’)3 group, wherein each R’ independently denotes C1-C6 alkyl, C3-C8 cycloalkyl, C5-C24 aryl, C7-C24 aralkyl, C5-C24 perhaloaryl, or two R’ are linked together to form a cycloalkyl ring containing a ring phosphorus atom; or L denotes an N-heterocyclic carbene ligand of formula (2a) or (2b): in which: each R3 and R4 independently denotes C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C2-C12 alkoxy or a halogen atom; each R5, R6, R7, R8, R9, R10 independently denotes a hydrogen atom, C1-C12 alkyl, C3-C12 cycloalkyl, C5-C20 aryl or C5-C20 heteroaryl, which is optionally substituted with at least one C1-C12 alkyl, C1-C12 perhaloalkyl, C1-C12 alkoxy or a halogen atom, or the groups R5, R6, R7, R8, R9, R10 are linked together to form a C4-C10 cyclic or C4-C12 polycyclic system; with the exception of compounds, in which simultaneously R1 denotes -NO2, R2 denotes isopropyl and L denotes is used in an amount not greater than 50 ppm.
4. The method according to claim 3, characterized in that the ruthenium complex is selected from the following compounds:
5. The method according to claim 3 or 4, characterized in that the reaction is carried out in an organic solvent, preferably selected from toluene, benzene, mesitylene, dichloromethane, ethyl acetate, methyl acetate, tert-butyl methyl ether and cyclopentyl methyl ether.
6. The method according to claim 3 or 4, characterized in that the reaction is carried out in the absence of a solvent.
7. The method according to any one of claims 3-6, characterized in that the reaction is carried out at a temperature of 0 to 150°C.
8. The method according to claim 7, characterized in that the reaction is carried out at a temperature of 20 to 120°C.
9. The method according to any one of claims 3-8, characterized in that the reaction time ranges from 1 minute to 24 hours.
10. The method according to any one of claims 3-9, characterized in that the compound of formula (1) is added to the reaction mixture in a solid form.
11. The method according to one of claims 3-5 or 7-9, characterized by the compound of formula (1) is added to the reaction mixture in form of a solution in an organic solvent.
12. The method according to claim 11, characterized in that the solution of the compound of formula (1) in an organic solvent is added to the reaction mixture by an infusion pump.
13. The method according to any one of claims 3-12, characterized in that it comprises conducting a metathesis reaction selected from ring closing metathesis (RCM), homometathesis (self-CM) and cross-metathesis (CM).
EP20845698.8A 2019-12-23 2020-12-17 Ruthenium complex and method of conducting olefin metathesis reactions with formation of an internal bond using the ruthenium complex as a catalyst Pending EP4081343A2 (en)

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