NEW STERICALLY ACTIVATED CHELATING RUTHENIUM COMPLEXES, METHOD OF THEIR PREPARATION AND THEIR USE IN OLEFIN METATHESIS REACTIONS

Abstract

The subject of the invention are new sterically activated chelating ruthenium complexes with the formula 1a, easy to obtain by efficient chemical reactions. The invention also concerns the method of obtaining and using ruthenium complexes with formula 1a as precatalysts and/or catalysts in a wide spectrum of known olefin metathesis reactions.

##STR00001##

Claims

1. A ruthenium complex selected from the group consisting of the structures 1a-Cl.sub.2, 1a-I.sub.2, 1c-Cl.sub.2, and 1c-I.sub.2: ##STR00039##

2. A method of reacting in an olefin metathesis reaction a compound according to claim 1 as a precatalyst or catalyst in the olefin metathesis reaction.

3. The method according to claim 2, wherein the reaction is carried out in an organic solvent, selected from toluene, benzene, mesitylene, dichloromethane, ethyl acetate, methyl acetate, tertbutyl-methyl ether, cyclopentyl-methyl ether or in a solvent-free system

4. The method according to claim 2, wherein the reaction is carried out at a temperature of 20 to 150 C. and in a time from 5 minutes to 24 hours, wherein compound according to claim 1 is used in an amount of not more than 0.1% molar and wherein compound according to claim 1 is added to the reaction mixture in solid or continuously by using vacuum pump as a solution and wherein the gaseous by-product of the reaction selected from ethylene, propylene and butylene is actively removed from the reaction mixture by inert gas barbotage or by the vacuum.

5. The method according to claim 3, wherein the reaction is carried out at a temperature of 20 to 150 C. and in a time from 5 minutes to 24 hours, wherein compound according to claim 1 is used in an amount of not more than 0.1% molar and wherein compound according to claim 1 is added to the reaction mixture in solid or continuously by using vacuum pump as a solution and wherein the gaseous by-product of the reaction selected from ethylene, propylene and butylene is actively removed from the reaction mixture by inert gas barbotage or by the vacuum.

6. The method of claim 2, wherein the olefin metathesis reaction is selected from the group consisting of a ring closing metathesis (RCM), a homometatesis, a cross metathesis (CM), an ethenolysis, an isomerization, a diastereoselective ring rearrangement metathesis (DRRM) reaction, an alken-alkin metathesis (en-yn) and a ring-opening metathesis polymerization (ROMP) reaction.

Description

EXAMPLES OF INVENTION

[0134] The following examples are provided only to illustrate the invention and to clarify its various aspects, not to limit it, and should not be equated with its entire scope, which is defined in the attached claims. In the following examples, unless otherwise indicated, standard materials and methods used in the field of invention were used or the recommendations of the manufacturers of specific reactants and devices were followed, and the use of methods known in the literature of the subject.

[0135] Diethyl malonate (S1), methyl Z-oleate, nG-SIPr, nG-SIPrI.sub.2, UltraCat and UltraNitroCat-I.sub.2 are commercially available compounds. The Phenoxy-Cl complex was obtained according to the literature method [H. Plenio et al., Adv. Synth. Catal., 2013, 355, 439-447]. S1 and methyl oleate were distilled from above activated-aluminium oxide under reduced pressure and stored over activated aluminium oxide. Pure Z-5-deken (99% Z isomer) was obtained by the literature method [A. Hoveyd et al., Organometallics 2011, 30, 1780-1782], then distilled from above activated aluminium oxide and stored over activated aluminium oxide. Other commercially available reagents were used without further purification. All reactions were carried out in an argon atmosphere. Toluene was washed with citric acid, water, dried with 4 molecular sieves and deoxidized with argon.

[0136] The composition of reaction mixtures was tested by gas chromatography using the PerkinElmer Clarus 680 GC apparatus equipped with the GL Sciences InertCap 5MS/NP capillary column.

[0137] The individual components of the reaction mixtures were identified by comparing retention times with commercial or isolated standards from reaction mixtures for which the structure was confirmed by NMR.

Example I

Reaction of Obtaining (Pre)Catalyst Ble-2

##STR00029##

[0138] Ligand A [Angew. Chem. Int. Ed. 2002, 41, 2509-2511] and the Ind-DMSO complex were obtained according to literature methods [WO2018038928A1].

[0139] The Ind-DMSO ruthenium complex (1.22 g, 1.47 mmol) was dissolved under an argon atmosphere in 12 mL of dichloromethane, followed by the addition of ligand A (0.70 g, 2.94 mmol, 2 equivalents). Stirred at boiling point for 2 hours was performed. Then the solvent was removed, and the remaining mixture was dried under reduced pressure. The raw product was applied to a chromatographic column in a small amount of dichloromethane. The mixture was chromatographically purified with an eluent (cyclohexane/ethyl acetate in a volumetric proportion of 9/1). Solvents were removed, green amorphous solid was mixed for 10 minutes with n-pentane (15 mL) and then cooled to 4 C. Filtered and washed with cold n-pentane. The product was crystallized from a DCM/MeOH mixture. A green, crystalline solid Ble-2 (0.75 g, 65%) was obtained.

[0140] .sup.1H NMR (CD.sub.2Cl.sub.2, 600 MHz) ppm: 16.55 (s, 1H); 7.59-7.56 (m, 2H); 7.48-7.46 (m, 2H); 7.43-7.35 (m, 8H); 6.99-6.96 (m, 1H); 6.87-6.86 (m, 1H); 4.45 (sept, 1H, J=6.6 Hz); 4.23 (s, 4H); 3.67-3.64 (m, 4H); 1.29 (d, 24H, J=6.6H); 0.93 (d, 6H, J=6.6 Hz).

Example II

Obtaining of Ligand F, in the Reaction Sequence: (i) Alkylation, (ii) Claisen Rearrangement, (iii) Alkylation, (iv) CC Bond Migration

##STR00030##

[0141] Potassium carbonate (1983 g, 1.4 equivalent), cesium carbonate (166 g, 0.05 equivalent) and allyl bromide (1063 ml, 1.2 equivalent) were added to the vigorously mixed solution of 2-isopropylphenol (1,1396 g, 1396 g, 1.3 mole, 1 equivalent) in acetonitrile (5.9 L [at C.sub.2-isopropylphenol=1.5 mola]). The resulting suspension was stirred at boiling point for 22 hours, then the mixture was concentrated to about 50% of the original volume and cooled to ambient temperature. TBME (3 L) was then added to precipitate inorganic by-products, which were filtered, flushed with TBME (1 L) and discarded. The combined extracts of acetonitrile and MTBE were evaporated, after which the raw product (B) was purified by distillation (oil bath temperature 94-96 C., p=510.sup.2 mbar). The first (20 g) and last fraction (60 g) were rejected. Yield: 1680 g (93%). Purity (based on GC): 98%. A round-bottomed 4 L double-necked flask containing 2-isopropylyloxyphenol B (2,1640 g) under argon atmosphere was placed in a heated Radley dish heated to 250 C. Accurate temperature measurements were made with a thermometer immersed in a reaction mixture. The reaction mixture began to boil at 196 C. and as a result of the reaction progressed it reached a boiling point of 216 C. The reaction was continued for 2 hours. Then the raw product C was purified by distillation (oil bath temperature 104-106 C., p=1.3-1.710.sup.2 mbar). Colorless oil, yield: 1200 g (73%). Purity (based on GC): 95%.

[0142] Potassium carbonate (1317 g, 1.4 equivalent), cesium carbonate (111 g, 0.05 equivalent) and benzyl bromide (890 ml, 1.1 equivalent) were added successively to a vigorously mixed solution of 2-allyl-6-isopropylphenol (C) (3,1200 g, 6.8 mol, 1 equivalent) in acetonitrile (ACN=3,65 1 [C.sub.2-allyl-6-isopropylphenol=1.5 mol]). The resulting suspension was heated at boiling point for 16 hours, then concentrated to about 50% of the original volume and cooled to ambient temperature. TBME (3 L) was then added to precipitate inorganic by-products, which were filtered, washed with TBME (1 L) and discarded. The solvents were evaporated on a rotary evaporator at 80 C. (residual benzyl bromide was partially removed). The raw product (E, 1800 g, 99%, yellow oil) was used in the next stage without further purification.

[0143] Carbonylchlorohydridotris(triphenylphosphine)ruthenium (32.2 g, 0.5 mol %) was added in 10 portions to a boiling solution of 2-allyl-6-isopropylbenzybenzene (E) (5,1800 g, 6.76 mol, 1 equivalent) in toluene (8.45 L, C=0.8 M) in 1 hour. Stirring was continued until the temperature of the reaction mixture returned to the ambient temperature. Then the post-reaction mixture was filtered through 500 g of silica gel. Toluene was removed on a rotary evaporator and the raw product F was purified by distillation (heating bowl temperature 160-170 C., p=710.sup.2 mbar), collecting light yellow oil. Efficiency: 1567 g, (yield 87%, E/Z=8/2). Purity (based on GC): 98%.

Example III

Reaction of Obtaining (Pre)Catalyst 1a-Cl.sub.2

##STR00031##

[0144] The Ind-DMSO complex (1.0 g, 1.20 mmol) in the argon atmosphere was dissolved in 10 mL of dichloromethane, and then the ligand F (0.417 g, 1.56 mmol, 1.3 equivalent) was added. Then the reaction mixture obtained in this way was stirred at boiling point for 2 hours. The solvent was removed, and the residue was dried under reduced pressure. The raw product was crystallized twice from a mixture of DCM/MeOH solvents. A green crystalline solid of 1a-Cl.sub.2 (0.76 g, yield of 79%) was obtained.

[0145] .sup.1H NMR (CD.sub.2Cl.sub.2, 600 MHz) ppm: 16.56 (s, 1H); 7.59-7.56 (m, 2H); 7.51-7.50 (m, 1H); 7.37-7.36 (m, 4H); 7.34-7.27 (m, 5H); 7.02 (t, 1H, J=7.2 Hz); 6.75-6.74 (m, 1H); 5.29 (s, 2H); 4.21 (s, 4H); 3.60-3.55 (m, 4H); 3.16 (sept, 1H, J=6.6 Hz); 1.27 (d, 12H, J=7.2H); 1.16 (d, 6H, J=6.6 Hz); 1.12 (d, 12H, J=6.0 Hz).

Example IV

Reaction of obtaining (pre)catalyst 1b-Cl.sub.2 and 1b-I.sub.2

##STR00032## ##STR00033##

[0146] To the solution of the UltraCat complex (1.0 g, 1.04 mmol) in toluene (7 mL) ligand F was added (0.33 g, 1.25 mmol, 1.25 mmol, 1.2 equivalent) and copper chloride (I) (0.155 g, 1.56 mmol, 1.5 equivalent). The reaction mixture was heated to 70 C. After 1 hour, the reaction mixture was cooled to ambient temperature and filtered through a thin layer of celite. Toluene was removed on a rotary evaporator. The residue was crystallized twice from the DCM/MeOH mixture. The resulting green solid (1b-Cl.sub.2) was dried under a high vacuum, then dissolved in acetone (15 mL) and sodium iodide (1.56 g, 10.43 mmol) was added. Then the whole was stirred at 40 C. for 3 hours. Acetone was removed and DCM was added to the residue. Filtered through Schott's funnel. The filtrate was evaporated and reconstituted in acetone (15 mL). Sodium iodide (1.56 g, 10.43 mmol) was added and stirred at 40 C. for 6 hours. Acetone was removed and DCM was added to the residue. Filtered through Schott's funnel. The filtrate was evaporated. The product (1b-I.sub.2) was crystallized from a DCM/MeOH mixture to obtain a dark green crystalline solid (0.486 g, with a yield of 51%).

Example V

Comparison of Reactivity of (Pre)Catalysts in the RCM Model Reaction

##STR00034##

[0147] The solution of diethyl malonate (S1) in toluene (10 mL, 0.1 M) was cooled to 0 C. and then a solution of (pre)catalyst (Ble-2, 1a-Cl.sub.2, or nG-SiPr at 0.1% mol) in toluene (100 L) was added. During the entire reaction, argon was passed through the reaction mixture to actively remove the ethylene emitted. At appropriate intervals of time, 0.2 mL of reaction mixture was taken and transferred to a vial containing 0.8 mL of ethyl-vinyl ether. The samples were analyzed using a gas chromatograph.

TABLE-US-00001 TABLE 1 Comparison of catalyst activity in the model RCM reaction Ble-2 1a-Cl.sub.2 nG-SiPr t[min] Q1 S1 Q1 S1 Q1 S1 2 6.7 92.5 6.9 92.5 1.7 97.6 4 12.4 87.0 15.1 84.2 1.9 97.4 6 20.4 78.8 22.6 76.7 2.3 97.0 8 28.7 70.7 31.3 67.9 3.0 96.3 10 36.5 62.8 39.6 59.7 3.4 95.9 20 63.3 36.1 67.1 32.3 7.3 92.0 30 74.3 25.0 75.3 24.0 12.5 86.8 60 85.2 14.1 84.9 14.4 26.7 72.6

Example VI

Reaction of Obtaining (Pre)Catalyst 1a-S.sub.2

##STR00035##

[0148] The entire reaction and isolation of the product was carried out in anaerobic conditions, under argon. DCM (1500 ml) was degassed with argon. The degassed DCM was supplemented with the 1a-Cl.sub.2 complex (250 g, 312 mmol) and the ligand G (125 g, 374 mmol, 1.2 equivalent). The whole was mixed for 60 minutes at ambient temperature. DCM (1500 ml) was degassed in a separate flask. With the help of a cannula, the reaction mixture was transferred to the sinter and filtered without air access to the 5 L three-necked flask with two caps with tap. One of the caps was connected to the argon line, and the other to the evaporator. The flask was rinsed after the reaction with previously degassed DCM. The sintered sludge was washed with degassed methanol (1 L). At the end of the filtration, there were 3 L of DCM and 1 L of MeOH in the flask. The flask was placed in a heating bowl heated to 40 C. and the DCM was slowly removed. After evaporation of DCM, the flask was filled with argon and the product was scraped off the walls with a spatula. Then, stirring, with the help of a cannula, the suspension was transferred to sinter and methanol was filtered. The sludge was washed with degassed methanol until the filtrate was light yellow, then the sludge was washed with degassed n-pentane until the filtrate was light yellow. Product 1a-S.sub.2 was transferred to the flask and dried under reduced pressure. Process efficiency 278 g, (95% yield) of the expected product 1a-S.sub.2 obtained in the form of brownish-yellow powder.

[0149] A spectrum of .sup.1H NMR was made in a degassed CD.sub.2Cl.sub.2. The disappearance of the characteristic signal from the benzylidene proton with a displacement of 16.56 ppm and the appearance of a new signal from the benzylidene proton with a displacement of 14.52 ppm were observed.

Example VII

Reaction of Obtaining (Pre)Catalyst 1e-S.sub.2

##STR00036##

[0150] The 1e-S.sub.2 complex was obtained according to the procedure described in example VI.

[0151] In this way, 1.4 g of the target product 1e-S.sub.2 with the yield of 99% was obtained.

[0152] A spectrum of .sup.1H NMR was made in a degassed CD.sub.2Cl.sub.2. The disappearance of the characteristic signal from the benzylidene proton with a displacement of 15.43 ppm and the appearance of a new signal from the benzylidene proton with a displacement of 14.41 ppm were observed.

Example VIII

Reaction of Obtaining (Pre)Catalyst 1d-S.sub.2

##STR00037##

[0153] The 1d-S.sub.2 complex was obtained according to the procedure described in example VI. In this way, 0.3 g of 1d-S.sub.2 product with the yield of 99% was obtained.

[0154] A spectrum of .sup.1H NMR was made in a degassed CD.sub.2Cl.sub.2. The disappearance of the characteristic signal from the benzylidene proton with a displacement of 16.56 ppm and the appearance of a new signal from the benzylidene proton with a displacement of 14.48 ppm were observed.

Example IX

[0155] Comparison of the effectiveness of complexes 1a-S.sub.2, 1d-S.sub.2, 1e-S.sub.2 in stereoretentive cross metathesis.

##STR00038##

[0156] The Z-5-dekene (3.0 mmol, 0,577 mL), methyl Z-oleate MO (1.0 mmol, 0,340 mL) and 0.07 mL hexadecane (internal standard) were placed in a round-bottomed flask under an argon atmosphere and heated to 45 C. Suitable complexes (1e-S.sub.2, 1a-S.sub.2, 1d-S.sub.2) were added in 5 ppm molar portions for a double bond of CC. After each portion, the reaction was carried out for 30 minutes, after which time a sample was taken for GC analysis. The results are presented in the table below. In each case, products with a Z/E isomer ratio of 99/1 were obtained.

TABLE-US-00002 TABLE 2 Comparison of the efficiency of stereoretentive catalysts. Loading Conversion No (Pre)cat. Time (min) (ppm/CC) (%) 1 1e-S.sub.2 30 5 7.0 2.2 2 1a-S.sub.2 30 5 7.0 3.0 3 1d-S.sub.2 30 5 10.5 0.2 4 1e-S.sub.2 60 10 22.5 2.5 5 1a-S.sub.2 60 10 42.0 5.0 6 1d-S.sub.2 60 10 43.2 5.3 3 1e-S.sub.2 90 15 43.0 3.6 6 1a-S.sub.2 90 15 82. 2.6 9 1d-S.sub.2 90 15 50.7 0.3