CA2541514C - Novel metathesis ruthenium catalyst - Google Patents
Novel metathesis ruthenium catalyst Download PDFInfo
- Publication number
- CA2541514C CA2541514C CA2541514A CA2541514A CA2541514C CA 2541514 C CA2541514 C CA 2541514C CA 2541514 A CA2541514 A CA 2541514A CA 2541514 A CA2541514 A CA 2541514A CA 2541514 C CA2541514 C CA 2541514C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- independently
- formula
- alkoxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
-
- 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
-
- 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
-
- 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
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0202—Polynuclearity
- B01J2531/0205—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
-
- 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
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
- B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2540/00—Compositional aspects of coordination complexes or ligands in catalyst systems
- B01J2540/30—Non-coordinating groups comprising sulfur
- B01J2540/34—Sulfonyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to new (pre)catalysts of ruthenium complexes of formula 1, 1 wherein L1, X1, X2, R1, R2, R3, Z and n are as defined in claim 1. The novel ruthenium complexes of formula 1 are convenient (pre)catalysts for metathesis reactions and can be applied i.e. for ring-closing metathesis, cross metathesis or ene-ine metathesis reactions.
Description
NOVEL METATHESIS RUTHENIUM CATALYST
TECHNICAL FIELD
This invention relates to ruthenium carbene complexes of formula 1, their synthesis and their practical use as catalysts for different types of metathesis reactions.
Ll 2 xi, I R
x Ri-c) (R3)õ
=
BACKGROUND INFORMATION
Great progress has been made in the last few years in the application of olefins metathesis in organic synthesis. Some ruthenium carbene complexes acting as (pre)catalysts have been developed, which possess a high activity in various metathesis reactions as well as a broad tolerance for a number of functional groups. This combination of characteristics is a basis for the usability of such (pre)catalysts in organic synthesis.
Moreover, for the practical application, especially in industrial scale, it is very desirable that these ruthenium complexes are stable for a longer period of time in the conditions of thermal load and that they can be stored, purified and applied without the atmosphere of protective gases.
Ruthenium complexes with the above mentioned characteristics are known in literature.
See J. Am. Chem. Soc. 2000, 122, 8168-8179 or Tetrahedron Lett. 2000, 41, 9973-9976.
However, it has been discovered that a better stability is connected with a lower catalytic activity. Such a limitation was found for example for the (pre)catalyst of the formula A (see Angew. Chemie Int. Ed. 2002, //4, 832).
CONFIRMATION COPY
Mes¨N NI/ N¨Mes Mes¨N y N¨Mes Clib, I
Ru_ I
Mes¨NyN¨Mes c CIr"f Ru_ O
1PrOl =ILINF Pr c,-4 , PrO 411 A
Next, (pre)catalysts of the formula B and C were described, which demonstrate a higher catalytic activity in comparison with the (pre)catalyst of the formula A. The catalysts A, B
and C contain an iso-propoxy group chelating the metal atom. The reason for a higher activity of the systems B and C is a steric hindrance caused by the presence of a phenyl or a (substituted) naphthyl group in ortho-position to the /so-propoxy group (Angew.
Chemie Int. Ed. 2002, 114, 832; Angew. Chemie Int. Ed. 2002, 114, 2509).
It has been found surprisingly that ruthenium complex (pre)catalysts of general formula 1, io demonstrate much higher catalytic activity in comparison to known highly active ruthenium complexes and that these complexes are at the same time thermal and air stable.
SUMMARY OF THE INVENTION
The present invention relates to novel ruthenium complexes of formula 1, their synthesis, the synthesis of all intermediates and the use of complexes of formula 1 as catalysts or as precatalysts, Ll 2 R
1.
R (t) (R3)n wherein:
X1 and X2 are anionic ligands;
TECHNICAL FIELD
This invention relates to ruthenium carbene complexes of formula 1, their synthesis and their practical use as catalysts for different types of metathesis reactions.
Ll 2 xi, I R
x Ri-c) (R3)õ
=
BACKGROUND INFORMATION
Great progress has been made in the last few years in the application of olefins metathesis in organic synthesis. Some ruthenium carbene complexes acting as (pre)catalysts have been developed, which possess a high activity in various metathesis reactions as well as a broad tolerance for a number of functional groups. This combination of characteristics is a basis for the usability of such (pre)catalysts in organic synthesis.
Moreover, for the practical application, especially in industrial scale, it is very desirable that these ruthenium complexes are stable for a longer period of time in the conditions of thermal load and that they can be stored, purified and applied without the atmosphere of protective gases.
Ruthenium complexes with the above mentioned characteristics are known in literature.
See J. Am. Chem. Soc. 2000, 122, 8168-8179 or Tetrahedron Lett. 2000, 41, 9973-9976.
However, it has been discovered that a better stability is connected with a lower catalytic activity. Such a limitation was found for example for the (pre)catalyst of the formula A (see Angew. Chemie Int. Ed. 2002, //4, 832).
CONFIRMATION COPY
Mes¨N NI/ N¨Mes Mes¨N y N¨Mes Clib, I
Ru_ I
Mes¨NyN¨Mes c CIr"f Ru_ O
1PrOl =ILINF Pr c,-4 , PrO 411 A
Next, (pre)catalysts of the formula B and C were described, which demonstrate a higher catalytic activity in comparison with the (pre)catalyst of the formula A. The catalysts A, B
and C contain an iso-propoxy group chelating the metal atom. The reason for a higher activity of the systems B and C is a steric hindrance caused by the presence of a phenyl or a (substituted) naphthyl group in ortho-position to the /so-propoxy group (Angew.
Chemie Int. Ed. 2002, 114, 832; Angew. Chemie Int. Ed. 2002, 114, 2509).
It has been found surprisingly that ruthenium complex (pre)catalysts of general formula 1, io demonstrate much higher catalytic activity in comparison to known highly active ruthenium complexes and that these complexes are at the same time thermal and air stable.
SUMMARY OF THE INVENTION
The present invention relates to novel ruthenium complexes of formula 1, their synthesis, the synthesis of all intermediates and the use of complexes of formula 1 as catalysts or as precatalysts, Ll 2 R
1.
R (t) (R3)n wherein:
X1 and X2 are anionic ligands;
-2-
3 PCT/EP2004/013621 Ll is a neutral ligand;
R1 is -01_20-alkyl, -C1_20-haloalkyl, -03.8-cycloalkyl or -C7-13-aralkyl;
R2 is H, -01_20-alkyl, -02_20-alkenyl, -C2_20-alkynyl or aryl;
R3 is -C1.6-alkyl, -01_6-alkoxy, aryl, F or Cl;
n is 0, 1, 2 or 3;
Z is -00-R4, -S02-R5 or -P0(R6)2;
R4 is -01_20-alkyl or -03.8-cycloalkyl, both optionally substituted by one or more groups each independently selected from F, Cl, Br, I or -C1_6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups each independently io selected from F, Cl, Br, I, -C1_6-alkyl, -C1_6-alkoxy, -NO2, -CN, -CF3, -0CF3 or -01_6-alkoxycarbonyl R5 is -01.8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkenyl, -01_6-alkoxy, -NO2, -ON, -CF3, -00F3, -01.6-alkoxycarbonyl, -S02-C1..6-alkyl or -S02-aryl; and R6 are each independently -01_20-alkyl, -03_8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkoxy, -NO2, -ON, -CF3, -0CF3, or -C1.6-alkoxycarbonyl; or zo R4, R5 and R6 are a group of formula 1' 1.
L, Rz x2' ¨Ru, 1.
t ' X
=
(R3)õ.
11, wherein:
X1' and X2' are anionic ligands;
L1' is a neutral ligand;
RI' is -01.20-alkyl, -01_20-haloalkyl, -03.8-cycloalkyl or -07-13-aralkyl;
R2' is H, -C1.20-alkyl, -02_20-alkenyl, -C2_20-alkynyl or aryl;
R3' is -01_6-alkyl, -01.6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
The compounds of formula 1 of the present invention may be used to catalyse olefin metathesis reactions including, but not limited to, ring opening metathesis polymerisation (ROMP), ring closing metathesis (RCM), depolymerisation of unsaturated polymers, synthesis of telechelic polymers, ene-ine metathesis and olefin synthesis.
Another embodiment of the present invention relates to novel 2-alkoxy-5-styrene derivatives of formula 2, which are intermediates for the preparation of complexes 1, (R12),, R2 z13 * Z
(R3)n 2 wherein:
R1, R2, R3, n and Z are defined as above and R12 is L, alkyl;
M IS 0, 1 or 2.
The partial formula (R12)m R2 represents an alkylene group in which one or both hydrogen atoms of the methylene group may be replaced by the group R12. Accordingly it covers the following alkylene groups:
)¨K
Ri2 A further aspect of the invention is the preparation of novel 2-alkoxy-5-styrene derivatives of formula 2, wherein:
R1 is -01_20-alkyl, -C1_20-haloalkyl, -03.8-cycloalkyl or -C7-13-aralkyl;
R2 is H, -01_20-alkyl, -02_20-alkenyl, -C2_20-alkynyl or aryl;
R3 is -C1.6-alkyl, -01_6-alkoxy, aryl, F or Cl;
n is 0, 1, 2 or 3;
Z is -00-R4, -S02-R5 or -P0(R6)2;
R4 is -01_20-alkyl or -03.8-cycloalkyl, both optionally substituted by one or more groups each independently selected from F, Cl, Br, I or -C1_6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups each independently io selected from F, Cl, Br, I, -C1_6-alkyl, -C1_6-alkoxy, -NO2, -CN, -CF3, -0CF3 or -01_6-alkoxycarbonyl R5 is -01.8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkenyl, -01_6-alkoxy, -NO2, -ON, -CF3, -00F3, -01.6-alkoxycarbonyl, -S02-C1..6-alkyl or -S02-aryl; and R6 are each independently -01_20-alkyl, -03_8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkoxy, -NO2, -ON, -CF3, -0CF3, or -C1.6-alkoxycarbonyl; or zo R4, R5 and R6 are a group of formula 1' 1.
L, Rz x2' ¨Ru, 1.
t ' X
=
(R3)õ.
11, wherein:
X1' and X2' are anionic ligands;
L1' is a neutral ligand;
RI' is -01.20-alkyl, -01_20-haloalkyl, -03.8-cycloalkyl or -07-13-aralkyl;
R2' is H, -C1.20-alkyl, -02_20-alkenyl, -C2_20-alkynyl or aryl;
R3' is -01_6-alkyl, -01.6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
The compounds of formula 1 of the present invention may be used to catalyse olefin metathesis reactions including, but not limited to, ring opening metathesis polymerisation (ROMP), ring closing metathesis (RCM), depolymerisation of unsaturated polymers, synthesis of telechelic polymers, ene-ine metathesis and olefin synthesis.
Another embodiment of the present invention relates to novel 2-alkoxy-5-styrene derivatives of formula 2, which are intermediates for the preparation of complexes 1, (R12),, R2 z13 * Z
(R3)n 2 wherein:
R1, R2, R3, n and Z are defined as above and R12 is L, alkyl;
M IS 0, 1 or 2.
The partial formula (R12)m R2 represents an alkylene group in which one or both hydrogen atoms of the methylene group may be replaced by the group R12. Accordingly it covers the following alkylene groups:
)¨K
Ri2 A further aspect of the invention is the preparation of novel 2-alkoxy-5-styrene derivatives of formula 2, wherein:
-4-= A substituted 2-hydroxy-5-benzaldehyde 3 is alkylated by a R1V, wherein R1 has the meaning given for formula 1 and V is a leaving group selected from halogen atoms, C1_6-fluoroalkyl-S(0)-0-, aryl-S(0)-0- or aryl-S(0)2-O-.
0¨ 0¨
Z R1V *Z
(R3) Riõ (R3)n = The substituted 2-alkoxy-5-benzaldehyde of formula 4 is then treated with an olefination reagent of formula (R12)m wherein R4 and m has the meaning given for formula 2 and W is a leaving group suitable for olefination reactions; to yield formula 2, R2 (R12)m R2 0_ Z olefination r0 *
R1Ri (R3)n (R3),, = Compound 2 can then be reacted with a ruthenium complex of formula 5 to result in the ruthenium complex of the formula 1 in which L1 and L2 are neutral ligands;
R13 is H, -C1_20-alkyl, -C2_20-alkenyl, -C2.20-alkynyl or aryl; R14 is aryl, vinyl or allenyl and X1 and X2 are anionic ligands.
0¨ 0¨
Z R1V *Z
(R3) Riõ (R3)n = The substituted 2-alkoxy-5-benzaldehyde of formula 4 is then treated with an olefination reagent of formula (R12)m wherein R4 and m has the meaning given for formula 2 and W is a leaving group suitable for olefination reactions; to yield formula 2, R2 (R12)m R2 0_ Z olefination r0 *
R1Ri (R3)n (R3),, = Compound 2 can then be reacted with a ruthenium complex of formula 5 to result in the ruthenium complex of the formula 1 in which L1 and L2 are neutral ligands;
R13 is H, -C1_20-alkyl, -C2_20-alkenyl, -C2.20-alkynyl or aryl; R14 is aryl, vinyl or allenyl and X1 and X2 are anionic ligands.
-5-t I
(R12) R2 A Ru¨\
/ ¨
1,e ¨ µ,2 I R2 x1" R14 R14 A/11,m õ0 Z 5 Ri (R3)n (R3),, Optionally, the obtained compound of formula 1 can then be reacted with a different neutral ligand L1 to replace the neutral ligand Ll that is present in the compound of formula 1 and thereby obtain a different compound of formula I.
The compounds herein described may have asymmetric centres. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in io optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention.
Cis and Trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms.
All chiral, diastereorneric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.
BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is a graph comparing the cyclisation speed of 22 when using a ruthenium catalyst according to the present invention versus using a known ruthenium catalyst 1i (see Example 9).
(R12) R2 A Ru¨\
/ ¨
1,e ¨ µ,2 I R2 x1" R14 R14 A/11,m õ0 Z 5 Ri (R3)n (R3),, Optionally, the obtained compound of formula 1 can then be reacted with a different neutral ligand L1 to replace the neutral ligand Ll that is present in the compound of formula 1 and thereby obtain a different compound of formula I.
The compounds herein described may have asymmetric centres. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in io optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention.
Cis and Trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms.
All chiral, diastereorneric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.
BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is a graph comparing the cyclisation speed of 22 when using a ruthenium catalyst according to the present invention versus using a known ruthenium catalyst 1i (see Example 9).
-6-DETAILED DESCRIPTION OF THE INVENTION
Terms not specifically defined herein should be given the meanings that would be given to them by one of skill in the art in light of the disclosure and the context. As used in the specification, however, unless specified to the contrary, the following terms have the meaning indicated and the following conventions are adhered to.
In the groups, radicals, or moieties defined below, the number of carbon atoms is often specified preceding the group, for example, -C1-6 alkyl means an alkyl group or radical having 1 to 6 carbon atoms. Unless otherwise specified below, conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups.
The term "optionally substituted" as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valence is not exceeded, and that the substitution results in a stable compound.
The term "aryl" as used herein, either alone or in combination with another substituent, means either an aromatic monocarbocyclic system or aromatic multicarbocyclic systems.
For example, aryl includes a phenyl or a naphthyl ring system.
The term "heteroaryl" as used herein, either alone or in combination with another substituent, means a monovalent substituent derived by removal of a hydrogen, especially if a the annelated connection noted, then it means a divalent substituent derived by removal of two hydrogen, from a five-, six-, or seven-membered saturated or unsaturated (including aromatic) heterocycle containing carbon atoms and from one to four ring heteroatoms selected from nitrogen, oxygen and sulphur. Examples of suitable heterocycles include: tetrahydrofuran, thiophene, diazepine, isoxazole, piperidine, dioxane, morpholine, pyrimidine or
Terms not specifically defined herein should be given the meanings that would be given to them by one of skill in the art in light of the disclosure and the context. As used in the specification, however, unless specified to the contrary, the following terms have the meaning indicated and the following conventions are adhered to.
In the groups, radicals, or moieties defined below, the number of carbon atoms is often specified preceding the group, for example, -C1-6 alkyl means an alkyl group or radical having 1 to 6 carbon atoms. Unless otherwise specified below, conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups.
The term "optionally substituted" as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valence is not exceeded, and that the substitution results in a stable compound.
The term "aryl" as used herein, either alone or in combination with another substituent, means either an aromatic monocarbocyclic system or aromatic multicarbocyclic systems.
For example, aryl includes a phenyl or a naphthyl ring system.
The term "heteroaryl" as used herein, either alone or in combination with another substituent, means a monovalent substituent derived by removal of a hydrogen, especially if a the annelated connection noted, then it means a divalent substituent derived by removal of two hydrogen, from a five-, six-, or seven-membered saturated or unsaturated (including aromatic) heterocycle containing carbon atoms and from one to four ring heteroatoms selected from nitrogen, oxygen and sulphur. Examples of suitable heterocycles include: tetrahydrofuran, thiophene, diazepine, isoxazole, piperidine, dioxane, morpholine, pyrimidine or
-7-The term "heteroaryl" also includes a heterocycle as defined above fused to one or more other cycle be it a heterocycle or any other cycle. One such examples includes indole or thiazolo[4,5-N-pyridine. Although generally covered under the term "Heteroaromatic ring", the term "heteroaryl" as used herein precisely defines an unsaturated heterocycle for which the double bonds form an aromatic system. Suitable example of heteroaromatic system include: quinoline, indole, pyridine, /, 11 \
. N-N . N . . 0 ; or io The term "halogen" as used herein means a halogen substituent selected from fluor , chloro, bromo or iodo.
The term "-C1..20-alkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing frorn one to twenty carbon atoms. The term "-C1_6-alkyl" as used herein has the same meaning as the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred. The terms -C1_20-alkyl or -C1.6-alkyl can include i.e. methyl, ethyl, propyl, butyl, hexyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl or 1, 1-dimethylethyl.
The term "-C2_20-alkenyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkenyl substituents containing from two to twenty carbon atoms and at least one double bond. The term "-C2.6-alkenyl" as used herein has the same meaning as the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred. The terms -C1_20-alkenyl or -C1.6-alkenyl can include i.e. vinyl or allenyl.
The term "-C2_20-alkynyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkynyl substituents containing from two to twenty carbon atoms and at least one triple bond. The term "-C2_6-alkynyl" as used herein has the same meaning then the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred.
. N-N . N . . 0 ; or io The term "halogen" as used herein means a halogen substituent selected from fluor , chloro, bromo or iodo.
The term "-C1..20-alkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing frorn one to twenty carbon atoms. The term "-C1_6-alkyl" as used herein has the same meaning as the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred. The terms -C1_20-alkyl or -C1.6-alkyl can include i.e. methyl, ethyl, propyl, butyl, hexyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl or 1, 1-dimethylethyl.
The term "-C2_20-alkenyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkenyl substituents containing from two to twenty carbon atoms and at least one double bond. The term "-C2.6-alkenyl" as used herein has the same meaning as the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred. The terms -C1_20-alkenyl or -C1.6-alkenyl can include i.e. vinyl or allenyl.
The term "-C2_20-alkynyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkynyl substituents containing from two to twenty carbon atoms and at least one triple bond. The term "-C2_6-alkynyl" as used herein has the same meaning then the above mentioned term but contains less carbon atoms, precisely a maximum of six carbon atoms and is therefore preferred.
-8-The term "-C3.8-cycloalkyl" as used herein, either alone or in combination with another substituent, means a cycloalkyl substituent containing five or six carbon atoms and includes i.e. cyclopentyl or cyclohexyl.
The term "-C1_6-alkoxy" as used herein, either alone or in combination with another substituent, means the substituent -C1-6-alkyl-0- wherein alkyl is as defined above containing up to six carbon atoms. Alkoxy includes methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy or 1, 1-dimethylethoxy.
io The term "-C7..13-aralkyl" as used herein, either alone or in combination with another substituent, means the substituent -Aryl-C1-5-alkyl- wherein alkyl is as defined above containing up to six carbon atoms. Aralkyl includes benzyl, phenylethyl, phenylpropyl, 1-phenyl-1-methylethyl or phenylbutyl.
The term "-C1_20-haloalkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing up to twenty carbon atoms having one or more hydrogens substituted for a halogen selected from bromo, chloro, fluoro or iodo. Preferably the term -C1_20-haloalkyl represents -C1_8-fluoroalkyl. The term "-C1_8-fluoroalkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing up to six carbon atoms having one or more hydrogens substituted by a flour atom such as 2-fluorethyl or 2,2,2-trifluorethyl. Preferably the terms -C1.20-haloalkyl and -C1.8-fluoroalkyl represent -C1_5-perflouroalkyl such as trifluoromethyl or pentafluoroethyl.
ADDITIONAL EMBODIMENTS
Preferred are compounds of general formula 1, wherein R4 is -C1_20-alkyl or -C3.8-cycloalkyl, both optionally substituted by one or more groups each independently selected from F, Cl, Br, I or -C1_6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups each independently
The term "-C1_6-alkoxy" as used herein, either alone or in combination with another substituent, means the substituent -C1-6-alkyl-0- wherein alkyl is as defined above containing up to six carbon atoms. Alkoxy includes methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy or 1, 1-dimethylethoxy.
io The term "-C7..13-aralkyl" as used herein, either alone or in combination with another substituent, means the substituent -Aryl-C1-5-alkyl- wherein alkyl is as defined above containing up to six carbon atoms. Aralkyl includes benzyl, phenylethyl, phenylpropyl, 1-phenyl-1-methylethyl or phenylbutyl.
The term "-C1_20-haloalkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing up to twenty carbon atoms having one or more hydrogens substituted for a halogen selected from bromo, chloro, fluoro or iodo. Preferably the term -C1_20-haloalkyl represents -C1_8-fluoroalkyl. The term "-C1_8-fluoroalkyl" as used herein, either alone or in combination with another substituent, means acyclic, straight or branched chain alkyl substituents containing up to six carbon atoms having one or more hydrogens substituted by a flour atom such as 2-fluorethyl or 2,2,2-trifluorethyl. Preferably the terms -C1.20-haloalkyl and -C1.8-fluoroalkyl represent -C1_5-perflouroalkyl such as trifluoromethyl or pentafluoroethyl.
ADDITIONAL EMBODIMENTS
Preferred are compounds of general formula 1, wherein R4 is -C1_20-alkyl or -C3.8-cycloalkyl, both optionally substituted by one or more groups each independently selected from F, Cl, Br, I or -C1_6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups each independently
-9-selected from F, Cl, Br, I, -C1_6-alkyl, -C1_6-alkoxy, -NO2, -CN, -CF3, -0CF3 or -C1_6-alkoxycarbonyl R5 is -C1_8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkyl, -C1_6-alkenyl, -NO2, -CN, -CF3, -C1_6-alkoxycarbonyl, -S02-C1_6-alkyl, -S02-aryl or a group of formula 1'; and R6 areeach independently -C1_20-alkyl, -C3_8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups each independently selected from F, Cl, Br, I, -C1_6-alkyl, -C1_6-alkoxy, -NO2, -CN, -CF3, -0CF3, or -C1_6-alkoxycarbonyl.
Also preferred are compounds of general formula 1, wherein Z is -CO-R4 or -P0(R6)2; and R4 and R6 are a group of formula 1'.
In some invention embodiments, L1 is P(R11)3; and R" is phenyl or cyclohexyl.
Preferred are compounds of formula la, wherein LI, )(1, x2, RI, R2, K-3 , Z and n are defined as above.
R1,0 Z
(R3)n la More preferred are the above mentioned compounds of general formula 1 or la wherein LI is P(RI1)3 and R" are each independently -C1_6-alkyl, -C3_8-cycloalkyl or aryl; or LI is a ligand of formula 6a, 6b, 6c or 6d, , ) ________ ( , )-( , )-( , , R-N N-R8 R-N N-R8 R-N N./N-R - R-N N-RNr _ 6a 6b 6c 6d wherein 10a R7 and R8 are each independently H, -C2.20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1.6-alkyl, -C1_6-alkoxy or halogen; particularly R9 and R19 are each independently H, -C1_20-alkyl, -C2_20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1_6-alkyl, -C1_6-alkoxy or halogen or R9 and R19 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring.
Y and Y' are halogen.
Particularly preferred are compounds wherein R7 and R8 are each independently H, -C2_6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1.6-alkyl, -C16alkoxy or halogen;
R9 and R19 are each independently H, -C1_6-alkyl, -C2_6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1_6-alkyl, -C1_6-alkoxy or halogen or R9 and R19 together with the carbon atoms to which they are attached are combined to form a carbocyclic 5 to 7 membered ring.
Most preferred are compounds of general formula 1 or 1a, wherein = R1 is iso-propyl;
= R2 is H, -C1.6-alkyl or aryl, in particular H;
= X1- and X.2.1 are halogen, particularly chlorine;
= Ll is P(cyclohexy1)3 or L1 is a group of formula 6a, 6b, 6c or 6d, more preferred a group of formula 6a;
7 )---( 8 R¨N. N¨R
6a = wherein R7 and R8 are each 2,4,6-trimethylphenyl; and R9 and R1 are each H.
= R7 and R8 are 2-methylbenzene, 2, 6-dimethylbenzene or 2, 4, 6-trimethylbenzene;
= n is O.
In particular most preferred are compounds of general formula 1 or 1a, wherein = R1 is a iso-propyl;
= R2 is H;
= X1 and X2 are chlorine;
= L1 is a group of formula 6a;
7H8N-R 6a = wherein R7 and R8 are each 2,4,6-trimethylpheny and R9 and R19 are each H;
= R7 and R8 are 2-methylbenzene, 2, 6-dimethylbenzene or 2, 4, 6-trimethylbenzene;
= n is O.
Preferred compounds of formula 2 are compounds of formula 2a, wherein R1, R2, R3, R12, Z, m and n are dafiried-a abb7e.-(R12) R2 32a More preferred are compounds of general formula 2 or 2a, wherein = R1 is a iso-propyl group; and / or = R2 is H, -C1_6-alkyl or aryl, in particular R2 has the meaning of a hydrogen atom;
and/or = ,-,12 K is -C1_6-alkyl, in particular methyl or ethyl; and / or = n is 0 and / or = m is O.
Additional embodiments are compounds of formula 2 or 2a wherein:
= R1 is iso-propyl;
= R2 is H;
= M iS 0; and = n is O.
Furthermore preferred is a process for manufacturing complexes of formula 1 or la, wherein a compound of general formula 2 or 2a, is reacted with a ruthenium complex of formula 5 , x', I r x R14 wherein Ll and L2 are neutral ligands R13 is H, -C2_20-alkenyl, -C2..20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl; and X1 and X2 are anionic ligands;
optionally in the presence of a different neutral ligand More preferred is the above mentioned synthesis of a ruthenium complex of formula 1, when the process is carried out:
= in the presence of a copper salt, in particular CuCl; and / or = in a halogenated or an aromatic solvent, particularly selected from methylene chloride, chloroform, benzene, toluene, xylene, mesitylene or mixtures thereof; and / or = at a temperature from 0 to 100 C, in particular at a temperature from 10 to 80 C, more particular at a temperature from 20 to 60 C; and / or = in a time period from 1 to 24h, in particular 1 to10h, more particular 1 to 4h.
Most preferred is the above mentioned synthesis of a ruthenium complex, wherein the reaction is carried out in one vessel by mixing the ligand of formula 6a, 6b, 6c or 6d with a solid complex of formula 5, wherein both ligands Ll and L2 are phosphines of formula P(R11)3, wherein R11 has the meaning as above and thereafter adding a ligand of formula 2 or 2a.
=
One preferred variation of the above mentioned synthesis of a ruthenium complex is the generation of the ligands of general formula 6a, 6b, 6c or 6d in situ from the stable salts of the formulae 7a, 7b, 7c or 7d, R9 R19 Rs R10 Y Y R10 7 Hõ 7 )z('+ 7 -)-4 - 7 1/"=.( 8 R¨N
R¨N N¨R8 R"¨N N¨R R¨N N¨R
7a 7b 7c 7d wherein the anion is selected from formiate, acetate, trifluoro-acetate or another acid group, a halogen or [BF4r. Therefore, the salt is preferably in form of a suspension i n solvents such as aliphatic or aromatic hydrocarbons, preferably hexane, reacted with a strong base, selected from alkali metal hydrides, alkaline earth metal hydrides or alcoholates, particularly potassium tert-pentanolate, potassium tert-amylate or potassium tert-butanolate. Thereafter reaction is continued by adding a solid complex of formu la 5, wherein both ligands L1 and L2 are phosphines of formula P(R11)3 and thereafter adding a ligand of formula 2 or 2a, to yield a compound of general formula 1 or la.
Moreover preferred is a process for manufacturing intermediates, which comprises -the steps of a) alkylating a compound of general formula 3, with a reagent of formula R-1V (9) to form a intermediate of formula 4, and b) reacting 4 with an olefination reagent of formula 10 to yield a compound of the general formula 2, R2 R2 (R12)m R2 (R12)m Ri R1 (R3), (R3), (R3), wherein R1, R2, R3, R12, Z, m and n of formula 2, 3, 4, 9 and 10 are defined as above and W is a leaving group suitable for olefination reactions; and.
V is halogen, -C.6-alkyl-S(0)-O-, -C1_6-fluoroalkyl-S(0)-0-, aryl-S(0)-0- or aryl-S(0)2-0-.
More preferred is a process, wherein the above mentioned step a) is carried out:
= in an aprotic solvent, in particular selected from DMF, DMSO, acetone, acetonitrile, ethyl acetate, glycol ether, methanol, ethanol or mixtures thereof, more particular the solvent is DMF; or = in a biphasic solvent system fitted with a phase transfer catalyst; or = in presence of a catalyst, in particular the catalyst is selected from Cs2CO2, CsF, quaternary ammonium salts, crown ethers or cryptands, more particular Cs2003;
or = in the presence of an alkali metal carbonate or an alkali hydroxide, in particular io selected from Na2CO3, K2CO3, Li2CO3, Cs2CO3, NaOH, KOH, Li0H, Cs0H; or = in a time period from 1 to 24h, in particular 8 to24h, more particular 16 to 24h.
= at a temperature from 0 to 150 C, in particular at a temperature from 10 to 100 C, more particular at a temperature from 20 to 80 C; or Starting from compound 4, compound 2 is available under Tebbe, Wittig, Wittig-Horner, Wittig-Horner-Emmons or Peterson conditions, but preferred is a process, wherein the above mentioned step b) is carried out:
= in a solvent selected from alcohols, glycol ethers or cyclic ethers, preferred is THF; or = W is a leaving group suitable for olefination reactions according to Tebbe, with Tebbe's titanium reagent, or according to Wittig, with Wittig's phosphonium ylide reagent, more particular a leaving group selected from PPh3 or TiCp2; wherein Ph is substituted or unsubstituted phenyl and Cp is a substituted or unsubstituted cyclopentadienyl-anion, which can be found after reaction in its oxidised form.
Another preferred embodiment of the invention is a process for metathesis reactions of all types, comprising contacting an olefin with a catalyst of general formula 1;
in particular wherein the metathesis reaction is a ring closing or cross metathesis reaction.
The following examples are to illustrate various embodiments of the present invention and are not to be understood as limiting the present invention in a way.
a) 4-Methoxy-benzene-phosphonic-acid-diethylester is prepared in analogy to Chem.
Ber. (1970) 103, 2428-2436.
b) 4-Methoxy-benzene-phosphonic-acid-diethylester (1.3 g, 12.3 mmole), SOCl2 (14.6 g, 123 mmole), and DMF (0,9 ml) are heated to reflux under argon for 4 hours.
After removal of remaining SOC12 under vacuum, 2,4 g crude 4-Methoxy-benzene-phosphonic-acid-dichloride is obtained.
c) 10.8 g 4-Brom-chlorbenzene is reacted with 1.38 g magnesium in 100 ml THF
to Grignard reagent. The resulting mixture is added under argon over 40 minutes to a cooled solution (-78 C) of 4-Methoxy-benzenephosphonic-acid-dichloride (2.42 g) and THF (60 m1). Thereafter the mixture is stirred for 10 h at room temperature. A
saturated NH4CI solution is added and the solvent removed under vacuum. The residue is threatened with 100 ml CH2Cl2, filtered through silica gel and dried again.
Product is purified by column chromatography (hexane / ethyl acetate, 4 : 2).
2.15 g of pure 4-Methoxyphenyl-bis(4-chlorophenyI)-phosphinoxid is obtained.
mP== 106-107 C.
d) 4-Methoxyphenyl-bis(4-chloropheny1)-phosphinoxid (1.84 g, 4.88 mmole) and CH2Cl2 (30 ml) are cooled to -78 C. BBr3 (1,84g, 7,32 mmole) is added and the resulting mixture is stirred for 26 h at r.t.. I-120 (30 ml) is added and CH2Cl2 removed under stirring at 80 C. After 6 h the mixture is cooled down and the product precipices. Solid residue is purified by column chromatography (methanol / ethyl acetate / H20, 5 : 50:
0,5). 1.26 g of pure 4-Hydroxyphenyl-bis(4-chlorophenyI)-phosphinoxid is obtained.
mP' = 116-119 C
a) K2CO3 (298 mg, 2.2 mmole), Cs2CO3 (104 mg, 0.32 mmole) and 8 (R6= p-Cl-phenyl, 400 mg, 1.1 mmole) are placed in a flask. DMF (5.5 ml) is added and the mixture is stirred about 5 minutes. After the time, ally! bromide (190 I, 2.2 mmole) is added and the mixture is stirred for another 24 h at 35 C. DMF is evaporated under vacuum, water (10 ml) is added and the mixture is extracted with ethyl acetate (3 x 25 ml). Combined extracts are dried and evaporated to dryness. 440 mg (99 %) of crude 9 (R6'= p-Cl-phenyl) is obtained.
P0(R6)2 P0(R6)2 , Br 1H NMR (400 MHz, CDCI3): 8 = 4.59 (dt, J = 5.4, J =1.5 Hz, 2H), 5.30-5.34 (m, 1H), 5.39-5.45 (m, 1H); 6.00-6.09 (m, 1H), 6.98-7.01 (m, 2H), 7.43-7.47 (m, 4H), 7.50-7.62 (m, 6H).
b) A solution of 9 (R6.= p-Cl-phenyl, 400 mg, 1.0 mmole) in 1,2,4-trichlorobenzene (5 ml) is heated under Argon at 200-210 C for 8 h. After cooling, n-pentane (ca. 40 ml) is added and a light-brown solid is formed, which is filtered-off and dried. 337 mg of crude 10 (R6'=
p-Cl-phenyl) is obtained.
P0(R6')2 \ P0(R6')2 HO
1H NMR (400 MHz, CD30D): 8 = 3.30-3.32 (m, 2H) , 4.96-4.98 (m, 1H), 4.99-5.02 (m, 1H), 5.87-5.97 (m, 1H) 6.90-6.93 (m, 1H), 7.23-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.54-7.62 (m, 8H) c) 10 (R6'.= p-Cl-phenyl, 300 mg; 0.75 mmole), RhC13-3H20 (19 mg, 0.075 mmole,
Also preferred are compounds of general formula 1, wherein Z is -CO-R4 or -P0(R6)2; and R4 and R6 are a group of formula 1'.
In some invention embodiments, L1 is P(R11)3; and R" is phenyl or cyclohexyl.
Preferred are compounds of formula la, wherein LI, )(1, x2, RI, R2, K-3 , Z and n are defined as above.
R1,0 Z
(R3)n la More preferred are the above mentioned compounds of general formula 1 or la wherein LI is P(RI1)3 and R" are each independently -C1_6-alkyl, -C3_8-cycloalkyl or aryl; or LI is a ligand of formula 6a, 6b, 6c or 6d, , ) ________ ( , )-( , )-( , , R-N N-R8 R-N N-R8 R-N N./N-R - R-N N-RNr _ 6a 6b 6c 6d wherein 10a R7 and R8 are each independently H, -C2.20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1.6-alkyl, -C1_6-alkoxy or halogen; particularly R9 and R19 are each independently H, -C1_20-alkyl, -C2_20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1_6-alkyl, -C1_6-alkoxy or halogen or R9 and R19 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring.
Y and Y' are halogen.
Particularly preferred are compounds wherein R7 and R8 are each independently H, -C2_6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1.6-alkyl, -C16alkoxy or halogen;
R9 and R19 are each independently H, -C1_6-alkyl, -C2_6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups independently selected from -C1_6-alkyl, -C1_6-alkoxy or halogen or R9 and R19 together with the carbon atoms to which they are attached are combined to form a carbocyclic 5 to 7 membered ring.
Most preferred are compounds of general formula 1 or 1a, wherein = R1 is iso-propyl;
= R2 is H, -C1.6-alkyl or aryl, in particular H;
= X1- and X.2.1 are halogen, particularly chlorine;
= Ll is P(cyclohexy1)3 or L1 is a group of formula 6a, 6b, 6c or 6d, more preferred a group of formula 6a;
7 )---( 8 R¨N. N¨R
6a = wherein R7 and R8 are each 2,4,6-trimethylphenyl; and R9 and R1 are each H.
= R7 and R8 are 2-methylbenzene, 2, 6-dimethylbenzene or 2, 4, 6-trimethylbenzene;
= n is O.
In particular most preferred are compounds of general formula 1 or 1a, wherein = R1 is a iso-propyl;
= R2 is H;
= X1 and X2 are chlorine;
= L1 is a group of formula 6a;
7H8N-R 6a = wherein R7 and R8 are each 2,4,6-trimethylpheny and R9 and R19 are each H;
= R7 and R8 are 2-methylbenzene, 2, 6-dimethylbenzene or 2, 4, 6-trimethylbenzene;
= n is O.
Preferred compounds of formula 2 are compounds of formula 2a, wherein R1, R2, R3, R12, Z, m and n are dafiried-a abb7e.-(R12) R2 32a More preferred are compounds of general formula 2 or 2a, wherein = R1 is a iso-propyl group; and / or = R2 is H, -C1_6-alkyl or aryl, in particular R2 has the meaning of a hydrogen atom;
and/or = ,-,12 K is -C1_6-alkyl, in particular methyl or ethyl; and / or = n is 0 and / or = m is O.
Additional embodiments are compounds of formula 2 or 2a wherein:
= R1 is iso-propyl;
= R2 is H;
= M iS 0; and = n is O.
Furthermore preferred is a process for manufacturing complexes of formula 1 or la, wherein a compound of general formula 2 or 2a, is reacted with a ruthenium complex of formula 5 , x', I r x R14 wherein Ll and L2 are neutral ligands R13 is H, -C2_20-alkenyl, -C2..20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl; and X1 and X2 are anionic ligands;
optionally in the presence of a different neutral ligand More preferred is the above mentioned synthesis of a ruthenium complex of formula 1, when the process is carried out:
= in the presence of a copper salt, in particular CuCl; and / or = in a halogenated or an aromatic solvent, particularly selected from methylene chloride, chloroform, benzene, toluene, xylene, mesitylene or mixtures thereof; and / or = at a temperature from 0 to 100 C, in particular at a temperature from 10 to 80 C, more particular at a temperature from 20 to 60 C; and / or = in a time period from 1 to 24h, in particular 1 to10h, more particular 1 to 4h.
Most preferred is the above mentioned synthesis of a ruthenium complex, wherein the reaction is carried out in one vessel by mixing the ligand of formula 6a, 6b, 6c or 6d with a solid complex of formula 5, wherein both ligands Ll and L2 are phosphines of formula P(R11)3, wherein R11 has the meaning as above and thereafter adding a ligand of formula 2 or 2a.
=
One preferred variation of the above mentioned synthesis of a ruthenium complex is the generation of the ligands of general formula 6a, 6b, 6c or 6d in situ from the stable salts of the formulae 7a, 7b, 7c or 7d, R9 R19 Rs R10 Y Y R10 7 Hõ 7 )z('+ 7 -)-4 - 7 1/"=.( 8 R¨N
R¨N N¨R8 R"¨N N¨R R¨N N¨R
7a 7b 7c 7d wherein the anion is selected from formiate, acetate, trifluoro-acetate or another acid group, a halogen or [BF4r. Therefore, the salt is preferably in form of a suspension i n solvents such as aliphatic or aromatic hydrocarbons, preferably hexane, reacted with a strong base, selected from alkali metal hydrides, alkaline earth metal hydrides or alcoholates, particularly potassium tert-pentanolate, potassium tert-amylate or potassium tert-butanolate. Thereafter reaction is continued by adding a solid complex of formu la 5, wherein both ligands L1 and L2 are phosphines of formula P(R11)3 and thereafter adding a ligand of formula 2 or 2a, to yield a compound of general formula 1 or la.
Moreover preferred is a process for manufacturing intermediates, which comprises -the steps of a) alkylating a compound of general formula 3, with a reagent of formula R-1V (9) to form a intermediate of formula 4, and b) reacting 4 with an olefination reagent of formula 10 to yield a compound of the general formula 2, R2 R2 (R12)m R2 (R12)m Ri R1 (R3), (R3), (R3), wherein R1, R2, R3, R12, Z, m and n of formula 2, 3, 4, 9 and 10 are defined as above and W is a leaving group suitable for olefination reactions; and.
V is halogen, -C.6-alkyl-S(0)-O-, -C1_6-fluoroalkyl-S(0)-0-, aryl-S(0)-0- or aryl-S(0)2-0-.
More preferred is a process, wherein the above mentioned step a) is carried out:
= in an aprotic solvent, in particular selected from DMF, DMSO, acetone, acetonitrile, ethyl acetate, glycol ether, methanol, ethanol or mixtures thereof, more particular the solvent is DMF; or = in a biphasic solvent system fitted with a phase transfer catalyst; or = in presence of a catalyst, in particular the catalyst is selected from Cs2CO2, CsF, quaternary ammonium salts, crown ethers or cryptands, more particular Cs2003;
or = in the presence of an alkali metal carbonate or an alkali hydroxide, in particular io selected from Na2CO3, K2CO3, Li2CO3, Cs2CO3, NaOH, KOH, Li0H, Cs0H; or = in a time period from 1 to 24h, in particular 8 to24h, more particular 16 to 24h.
= at a temperature from 0 to 150 C, in particular at a temperature from 10 to 100 C, more particular at a temperature from 20 to 80 C; or Starting from compound 4, compound 2 is available under Tebbe, Wittig, Wittig-Horner, Wittig-Horner-Emmons or Peterson conditions, but preferred is a process, wherein the above mentioned step b) is carried out:
= in a solvent selected from alcohols, glycol ethers or cyclic ethers, preferred is THF; or = W is a leaving group suitable for olefination reactions according to Tebbe, with Tebbe's titanium reagent, or according to Wittig, with Wittig's phosphonium ylide reagent, more particular a leaving group selected from PPh3 or TiCp2; wherein Ph is substituted or unsubstituted phenyl and Cp is a substituted or unsubstituted cyclopentadienyl-anion, which can be found after reaction in its oxidised form.
Another preferred embodiment of the invention is a process for metathesis reactions of all types, comprising contacting an olefin with a catalyst of general formula 1;
in particular wherein the metathesis reaction is a ring closing or cross metathesis reaction.
The following examples are to illustrate various embodiments of the present invention and are not to be understood as limiting the present invention in a way.
a) 4-Methoxy-benzene-phosphonic-acid-diethylester is prepared in analogy to Chem.
Ber. (1970) 103, 2428-2436.
b) 4-Methoxy-benzene-phosphonic-acid-diethylester (1.3 g, 12.3 mmole), SOCl2 (14.6 g, 123 mmole), and DMF (0,9 ml) are heated to reflux under argon for 4 hours.
After removal of remaining SOC12 under vacuum, 2,4 g crude 4-Methoxy-benzene-phosphonic-acid-dichloride is obtained.
c) 10.8 g 4-Brom-chlorbenzene is reacted with 1.38 g magnesium in 100 ml THF
to Grignard reagent. The resulting mixture is added under argon over 40 minutes to a cooled solution (-78 C) of 4-Methoxy-benzenephosphonic-acid-dichloride (2.42 g) and THF (60 m1). Thereafter the mixture is stirred for 10 h at room temperature. A
saturated NH4CI solution is added and the solvent removed under vacuum. The residue is threatened with 100 ml CH2Cl2, filtered through silica gel and dried again.
Product is purified by column chromatography (hexane / ethyl acetate, 4 : 2).
2.15 g of pure 4-Methoxyphenyl-bis(4-chlorophenyI)-phosphinoxid is obtained.
mP== 106-107 C.
d) 4-Methoxyphenyl-bis(4-chloropheny1)-phosphinoxid (1.84 g, 4.88 mmole) and CH2Cl2 (30 ml) are cooled to -78 C. BBr3 (1,84g, 7,32 mmole) is added and the resulting mixture is stirred for 26 h at r.t.. I-120 (30 ml) is added and CH2Cl2 removed under stirring at 80 C. After 6 h the mixture is cooled down and the product precipices. Solid residue is purified by column chromatography (methanol / ethyl acetate / H20, 5 : 50:
0,5). 1.26 g of pure 4-Hydroxyphenyl-bis(4-chlorophenyI)-phosphinoxid is obtained.
mP' = 116-119 C
a) K2CO3 (298 mg, 2.2 mmole), Cs2CO3 (104 mg, 0.32 mmole) and 8 (R6= p-Cl-phenyl, 400 mg, 1.1 mmole) are placed in a flask. DMF (5.5 ml) is added and the mixture is stirred about 5 minutes. After the time, ally! bromide (190 I, 2.2 mmole) is added and the mixture is stirred for another 24 h at 35 C. DMF is evaporated under vacuum, water (10 ml) is added and the mixture is extracted with ethyl acetate (3 x 25 ml). Combined extracts are dried and evaporated to dryness. 440 mg (99 %) of crude 9 (R6'= p-Cl-phenyl) is obtained.
P0(R6)2 P0(R6)2 , Br 1H NMR (400 MHz, CDCI3): 8 = 4.59 (dt, J = 5.4, J =1.5 Hz, 2H), 5.30-5.34 (m, 1H), 5.39-5.45 (m, 1H); 6.00-6.09 (m, 1H), 6.98-7.01 (m, 2H), 7.43-7.47 (m, 4H), 7.50-7.62 (m, 6H).
b) A solution of 9 (R6.= p-Cl-phenyl, 400 mg, 1.0 mmole) in 1,2,4-trichlorobenzene (5 ml) is heated under Argon at 200-210 C for 8 h. After cooling, n-pentane (ca. 40 ml) is added and a light-brown solid is formed, which is filtered-off and dried. 337 mg of crude 10 (R6'=
p-Cl-phenyl) is obtained.
P0(R6')2 \ P0(R6')2 HO
1H NMR (400 MHz, CD30D): 8 = 3.30-3.32 (m, 2H) , 4.96-4.98 (m, 1H), 4.99-5.02 (m, 1H), 5.87-5.97 (m, 1H) 6.90-6.93 (m, 1H), 7.23-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.54-7.62 (m, 8H) c) 10 (R6'.= p-Cl-phenyl, 300 mg; 0.75 mmole), RhC13-3H20 (19 mg, 0.075 mmole,
10 %
mol) and p-toluene sulfonic acid (14 mg, 0.075 mmole, 10 % mol) are placed in a flask.
Et0H (5 ml) and H20 (0.5 ml) are added and the mixture is refluxed under Argon for 5h. A
dark red solution is formed. H20 (10 ml) is added and ethanol was evaporated.
The mixture is extracted with CH2Cl2 (5 x 15 ml), the combined extracts are washed with water, dried and filtered. The filtrate is evaporated. 294 mg (99 %) of 11 (R6= p-Cl-phenyl) is obtained.
401 P0(R6')2 P0(R6)2 HO HO
mol) and p-toluene sulfonic acid (14 mg, 0.075 mmole, 10 % mol) are placed in a flask.
Et0H (5 ml) and H20 (0.5 ml) are added and the mixture is refluxed under Argon for 5h. A
dark red solution is formed. H20 (10 ml) is added and ethanol was evaporated.
The mixture is extracted with CH2Cl2 (5 x 15 ml), the combined extracts are washed with water, dried and filtered. The filtrate is evaporated. 294 mg (99 %) of 11 (R6= p-Cl-phenyl) is obtained.
401 P0(R6')2 P0(R6)2 HO HO
11 1H NMR (400 MHz, CDCI3): 1.80 (dd, J = 6.6, J =1.6 Hz, 3H), 6.01-6.11 (m, 1H), 6.57 (d, J
=16.0 Hz, 1H), 6.92-6.96 (m, 1H), 7.14-7.20 (m, 1H), 7.36-7.46 (m, 4H), 7.53-7.59 (m, 5H) d) K2003 (182 mg, 1.3 mmole), Cs2CO3 (83 mg, 0.26 mmole), and 11 (R6= p-Cl-phenyl, 270 mg, 0.67 mmole) are placed in flask. DMF (3.0 ml) is added and the mixture is stirred about 5 min.. Thereafter, isopropyl iodide (150 1, 1.5 mmole) is added and the mixture is stirred for 22 h at 35 C. H20 (6 ml) is added and the mixture is extracted with ethyl 10 acetate (3 x 15 ml). Combined extracts are dried and evaporated to dryness. Product is purified by column chromatography (ethyl acetate / cyclohexane, 1 : 1). 155 mg (52 %) of pure 12 (R6'= p-Cl-phenyl) is obtained.
P0(R6)2 -3. P0(R6')2 13C NMR (100 MHz, CDC13): 5 = 19.0, 21.9, 70.6, 112.8(d, J = 13 Hz), 121.2, 122.3, 124.8, 128.0, 128.8 (d, J = 13 Hz), 130.3, 130.7, 131.7,133.3 (d, J= 11 Hz), 138.6, 157.7 A solution of t-Butyl lithium (0.8 mmole) in 5 ml of Et20 is dropped slowly to a solution of 11' (0.4 mmole, 96.5 mg) in 2 ml THF, at -78 C. 15 min later P0(R6')2 (R6.=
phenyl, 0.8 mmole, 189.3 mg) in 10 ml of THF is added slowly. The reaction mixture is stirred for 30 min at -78 C an then allowed under stirring to warm up to room temperature within 3 h.
Aqueous, saturated NH4C1(6m1) is added, the THF removed and the residue extracted with CH2C12 (3 x 10m1). The combined organic layers are washed with water, dried with anhydrous MgSO4, filtered and concentrated. The residue is purified by flash chromatography (50% Et0Ac in cyclohexane).
ill Br P0(R6)2 0 + P0(R6)2 0 11' 12' 13C-NMR (125 MHz, CDC13) 3= 22.0, 70.7, 112.8 (d, J = 13.4Hz), 115.6, 127.5 (d,. J =11.8 Hz). 127.7 (d, J = 18.9Hz), 128.4 (d, J =19 Hz), 131.1.
a) A solution of t-Butyl lithium (0.8 mmole) in 5 ml of Et20 is dropped slowly to a solution of 11' (0.4 mmole, 96.5 mg) in 2 ml THF, at -78 C. 15 min later 13 (0.8 mmole, 84.9 mg) in 10 ml of THF is added slowly. The reaction mixture is stirred for 30 min at -78 C an then allowed under stirring to warm up to room temperature overnight. Aqueous, saturated NH4CI (6m1) is added, the THF removed and the residue extracted with CH2Cl2 (3 x 10m1).
The combined organic layers are washed with water, dried with anhydrous MgSO4, filtered and concentrated. The residue is purified by flash chromatography (5% Et0Ac in cyclohexane).
Br =
+ lel 11' 13 14 13C-NMR (125 MHz, CDCI3) 3 = 22.2, 71.0, 76.0, 114.1, 114.3, 125.0, 126.5, 127M, 12T4, 127.8, 128.4, 131.9, 135.9, 143.9,154.7.
b) 14 (0.4 mmole, 0,1 g) was dissolved in 15 ml CH2Cl2, Pyridinium chromate (0.48 mmole, 103.4 mg) was added slowly and the resulting mixture was stirred at room temperature for 1 h. The solvent was removed and the residue purified by flash chromatography (5% Et0Ac in cyclohexane).
130-NMR (125 MHz, CDCI3) 8= 22.1, 70.8, 112.2, 115.4, 127.3. 128.2. 129.3.
129.6, 129.7, 131.2, 131.6, 131.8. 138.3, 158.7, 195.6.
Second generation Grubb's catalyst 16 (Mes = mesityl, 153 mg, 0.18 mmole) and CuCI
(31mg, 0.31 mmole) are placed in Schlock's flask. CH2Cl2 (3 ml) is added under Argon and a solution of 12 (R6'= p-Cl-phenyl, 86 mg, 0.19 mmole;) in CH2Cl2 (6 ml) is added. The solution is stirred at 40 C for 40 min under Argon. CuCI (10 mg) is added and the mixture is stirred for 1h. Thereafter solvent is evaporated, ethyl acetate (ca. 20 ml) is added, solid residues are filtered off and the filtrate is concentrated under vacuum. The product is purified by column chromatography (ethyl acetate / cyclohexane, 1 : 1). The product lb (R6= p-Cl-phenyl, 131 mg, 81 %) is obtained as a green solid.
F-1 Mes¨NN¨Mes Mes¨NN¨Mes CIN I
./ PO(R)2 CI it 0.1, CI tal ph 0 P0(R6)2 PCy3
=16.0 Hz, 1H), 6.92-6.96 (m, 1H), 7.14-7.20 (m, 1H), 7.36-7.46 (m, 4H), 7.53-7.59 (m, 5H) d) K2003 (182 mg, 1.3 mmole), Cs2CO3 (83 mg, 0.26 mmole), and 11 (R6= p-Cl-phenyl, 270 mg, 0.67 mmole) are placed in flask. DMF (3.0 ml) is added and the mixture is stirred about 5 min.. Thereafter, isopropyl iodide (150 1, 1.5 mmole) is added and the mixture is stirred for 22 h at 35 C. H20 (6 ml) is added and the mixture is extracted with ethyl 10 acetate (3 x 15 ml). Combined extracts are dried and evaporated to dryness. Product is purified by column chromatography (ethyl acetate / cyclohexane, 1 : 1). 155 mg (52 %) of pure 12 (R6'= p-Cl-phenyl) is obtained.
P0(R6)2 -3. P0(R6')2 13C NMR (100 MHz, CDC13): 5 = 19.0, 21.9, 70.6, 112.8(d, J = 13 Hz), 121.2, 122.3, 124.8, 128.0, 128.8 (d, J = 13 Hz), 130.3, 130.7, 131.7,133.3 (d, J= 11 Hz), 138.6, 157.7 A solution of t-Butyl lithium (0.8 mmole) in 5 ml of Et20 is dropped slowly to a solution of 11' (0.4 mmole, 96.5 mg) in 2 ml THF, at -78 C. 15 min later P0(R6')2 (R6.=
phenyl, 0.8 mmole, 189.3 mg) in 10 ml of THF is added slowly. The reaction mixture is stirred for 30 min at -78 C an then allowed under stirring to warm up to room temperature within 3 h.
Aqueous, saturated NH4C1(6m1) is added, the THF removed and the residue extracted with CH2C12 (3 x 10m1). The combined organic layers are washed with water, dried with anhydrous MgSO4, filtered and concentrated. The residue is purified by flash chromatography (50% Et0Ac in cyclohexane).
ill Br P0(R6)2 0 + P0(R6)2 0 11' 12' 13C-NMR (125 MHz, CDC13) 3= 22.0, 70.7, 112.8 (d, J = 13.4Hz), 115.6, 127.5 (d,. J =11.8 Hz). 127.7 (d, J = 18.9Hz), 128.4 (d, J =19 Hz), 131.1.
a) A solution of t-Butyl lithium (0.8 mmole) in 5 ml of Et20 is dropped slowly to a solution of 11' (0.4 mmole, 96.5 mg) in 2 ml THF, at -78 C. 15 min later 13 (0.8 mmole, 84.9 mg) in 10 ml of THF is added slowly. The reaction mixture is stirred for 30 min at -78 C an then allowed under stirring to warm up to room temperature overnight. Aqueous, saturated NH4CI (6m1) is added, the THF removed and the residue extracted with CH2Cl2 (3 x 10m1).
The combined organic layers are washed with water, dried with anhydrous MgSO4, filtered and concentrated. The residue is purified by flash chromatography (5% Et0Ac in cyclohexane).
Br =
+ lel 11' 13 14 13C-NMR (125 MHz, CDCI3) 3 = 22.2, 71.0, 76.0, 114.1, 114.3, 125.0, 126.5, 127M, 12T4, 127.8, 128.4, 131.9, 135.9, 143.9,154.7.
b) 14 (0.4 mmole, 0,1 g) was dissolved in 15 ml CH2Cl2, Pyridinium chromate (0.48 mmole, 103.4 mg) was added slowly and the resulting mixture was stirred at room temperature for 1 h. The solvent was removed and the residue purified by flash chromatography (5% Et0Ac in cyclohexane).
130-NMR (125 MHz, CDCI3) 8= 22.1, 70.8, 112.2, 115.4, 127.3. 128.2. 129.3.
129.6, 129.7, 131.2, 131.6, 131.8. 138.3, 158.7, 195.6.
Second generation Grubb's catalyst 16 (Mes = mesityl, 153 mg, 0.18 mmole) and CuCI
(31mg, 0.31 mmole) are placed in Schlock's flask. CH2Cl2 (3 ml) is added under Argon and a solution of 12 (R6'= p-Cl-phenyl, 86 mg, 0.19 mmole;) in CH2Cl2 (6 ml) is added. The solution is stirred at 40 C for 40 min under Argon. CuCI (10 mg) is added and the mixture is stirred for 1h. Thereafter solvent is evaporated, ethyl acetate (ca. 20 ml) is added, solid residues are filtered off and the filtrate is concentrated under vacuum. The product is purified by column chromatography (ethyl acetate / cyclohexane, 1 : 1). The product lb (R6= p-Cl-phenyl, 131 mg, 81 %) is obtained as a green solid.
F-1 Mes¨NN¨Mes Mes¨NN¨Mes CIN I
./ PO(R)2 CI it 0.1, CI tal ph 0 P0(R6)2 PCy3
12 16 lb LRMS (ESI, Me0H and 0H2Cl2): 896.1 (M+). HRMS (ESI, Me0H and CH2Cl2): calcd.
for C43H4502N2 35CI3 102RU (M+-CI): 859.1322; found 859.1358.
a) A solution of 17(500 mg) in 1,2,4-trichlorobenzene (8 ml) is heated at 210 C for 6 h.
After cooling, hexane (ca.80 ml) is added and 12 hours later a solid product is formed, which is filtered-off and dried. After chromatography (hexane / ethyl acetate, 3 : 2) 383 mg of the product 18 is obtained.
so2 / 401 so2 \ H
o 2 b) 18 (165 mg; 0.5 mmole), RhC13-3H20 (13.1 mg, 0.05 mmole, 10 % mol) and p-toluene sulfonic acid (6.8 mg, 0.05 mmole, 10 % mol) are placed in flask. Et0H (4.5 ml) and H20 (0.5 ml) are added and the mixture is refluxed for 3h. The mixture is evaporated to dryness, ethyl acetate is added and then filtered over 5 g of silica gel. The filtrate is evaporated. 157 mg of the product 19 is obtained.
\ 401 so2 \ so HO 2 \ HO
c) A solution of 19 (440 mg) in 1,2,4-trichlorobenzene (7 ml) is heated at 2100 for 6 h.
After cooling, hexane (ca.80 ml) is added and 12 hours later a solid product is formed, which is filtered-off and dried. After chromatography (hexane / ethyl acetate, 3 : 2) 258 g of the product 20 is obtained.
m: 147-148 C
P
d) 20 (258 mg; 0.75 mmole), RhC13-3H20 (19 mg, 0.075 mmole, 10 % mol) and p-toluene sulfonic acid (0.014 g, 0.075 mmole, 10 % mol) are placed in flask. Et0H (4.5 ml) and H20 (0.5 ml) are added and the mixture is refluxed for 3h. The mixture is evaporated to dryness, ethyl acetate added and then filtered over 5g of silica gel. The filtrate is evaporated. 235 mg of the product 21 is obtained.
\ s2 15 Second generation Grubb's catalyst 16 (Mes = mesityl, 140 mg, 0.166 mmole) and CuCI
(20mg, 0.20 mmole) are placed in Schlock's flask. CH2Cl2 (4 ml) is added under Argon and then a solution of 21(56 mg, 0.165 mmole) in CH2Cl2 (5 ml) is added. The solution is stirred at 40 C for 50 min under Argon. Thereafter, solvent is evaporated, ethyl acetate (ca. 10 ml) is added, white solid is filtered off and the filtrate is concentrated under 20 vacuum. The product is purified by column chromatography (15 %-30% ethyl acetate in cyclohexane). The product If (80 mg, 60 %) is obtained as a green solid.
Mes¨NN¨Mes Mes¨NN¨Mes CI I CI
10 (S2h Rtu¨
PCy, SO2 NO2 21 16 If Analogously to the processes described in the examples 1 to 7, the following compounds of formula 1c, Id, le, lg and lh are obtained. For instance, according to example 5 compound 12' is a ligand for complex 1c, compound 15 for complex Id or according to example 4 and 5 heptanone can be reacted with 11', oxidised and reacted with 16 to obtain complex le.
Mes-NN¨Mes = " Ru _ = t 0 POPh2 Mes-NNIrN¨Mes Ch, I
" Ru C _ = r". t 0 41 co Id Ch, I
" Ru _ = t le Mes-NNirN¨Mes Mes¨NN-Mes = " Ru_ __ RU õ
= t t CI
lg Mes-NNI/N¨Mes Cl /,I _ Ru _ Cr..- t ------c y 1 h Toluene is degassed by bubbling through nitrogen, 22 is dissolved in 10 ml of degassed toluene and added into the reaction flask. The solution is heated up to 80 C
and freshly prepared catalysts lc-h is added (1st) under nitrogen. After stirring for 60 min at the same to temperature the conversion is checked by HPLC. A second amount of catalysts 1c-h (2nd) is added under nitrogen and the conversion is checked 60 min later a second time by HPLC. Figure 1 is a graph comparing the cyclisation speed of 22. Table 1 shows the results of the HPLC analysis, wherein the catalyst 1c-h are compared with a known catalyst of formula 11 (Angew. Chem. Int. Ed. 2002, 41, 4038).
\ /1- sõCO2Me <rk A
4(CO2Me *:NH 0./NH
N Catalyst 1 b-h a -----0 ..:..
O
NH Nv c,., '-.._ II ,-S Br (:).,,,NH
b¨s 411 Br O
/---' Mes-NN-Mes CI, , I .
,Ru_ CI t I i Table 1 conversion [%Peak at 200nm]
catalyst 1st [mol%] 22 [mol] toluene [ml] 23 [60 min] 22 [60 min]
2nd [mol%] 23 [120 min] 22 [120 min]
1 c 0,4 0,0075 554 66,4 33,6 0,2 96,2 3,8 1d 0,4 0,0075 554 80,1 19,9 , 0,2 96,9 3,1 le 0,4 0,0075 554 89,9 10,1 0,2 98,9 1,1 1f (1st run) 0,4 0,0075 554 99,3 0,7 0,2 99,1 0,9 1f(2"d run) 0,4 0,0025 185 91,3 8,7 . 0,2 99,5 0,5 1 g 0,2 0,0075 554 - -0,1 98,8 1,2 1 h 0,4 0,0075 554 68,7 31,3 0,2 88,7 11,3 11(1st run) 0,4 0,0075 554 - -, 0,2 96,5 3,5 1i(2nd run) 0,4 0,015 1008 77,4 22,6 0,2 92,8 7,2 23.5 g Tetrakis hydroxy methyl phosphonium chloride (80%, 98.7 mmole) is dissolved in isopropanole (35 ml) under a nitrogen atmosphere. Then 12.1 g (98.7 mmole) of a 45%
KOH solution is added within 5 min while the solution is cooled (temperature 20-25 C).
After stirring the suspension for another 30 min under nitrogen, the mixture is filtered and the inorganic residue is washed with 20 ml of degassed isopropanole. The combined isopropanole solution is stored under a nitrogen atmosphere until use.
After cooling to 60 C 2.3 g (2.8 mmole) of the trihydroxy methyl phosphine (THP) solution is added to the reaction mixture of example 13. After stirring for 5 h at 60 C
the mixture is cooled to room temperature and extracted twice with 40 ml of degassed water, 40 ml of 0.5 M H CI, 40 ml of 0.5 M NaHCO3 solution, and 40 ml of water. Approx. 695 ml of toluene are distilled of at 50 C in vacuum (150 mbar) and the residue is treated at 50 C with 1.4 g of charcoal. The remaining liquid is added to 210 ml of pre-cooled methyl cyclohexane .(5 C). After stirring for further 60 min at 5 C the precipitate is filtered and washed with 100 ml of methyl cyclohexane (twice). The white solid is dried in vacuum at 30 C
to yield 23 as an almost white powder.
catalyst total yield % of 23 % of 22 1 c 96,2 86,02 1,20 Id 94,3 85,44 1,95
for C43H4502N2 35CI3 102RU (M+-CI): 859.1322; found 859.1358.
a) A solution of 17(500 mg) in 1,2,4-trichlorobenzene (8 ml) is heated at 210 C for 6 h.
After cooling, hexane (ca.80 ml) is added and 12 hours later a solid product is formed, which is filtered-off and dried. After chromatography (hexane / ethyl acetate, 3 : 2) 383 mg of the product 18 is obtained.
so2 / 401 so2 \ H
o 2 b) 18 (165 mg; 0.5 mmole), RhC13-3H20 (13.1 mg, 0.05 mmole, 10 % mol) and p-toluene sulfonic acid (6.8 mg, 0.05 mmole, 10 % mol) are placed in flask. Et0H (4.5 ml) and H20 (0.5 ml) are added and the mixture is refluxed for 3h. The mixture is evaporated to dryness, ethyl acetate is added and then filtered over 5 g of silica gel. The filtrate is evaporated. 157 mg of the product 19 is obtained.
\ 401 so2 \ so HO 2 \ HO
c) A solution of 19 (440 mg) in 1,2,4-trichlorobenzene (7 ml) is heated at 2100 for 6 h.
After cooling, hexane (ca.80 ml) is added and 12 hours later a solid product is formed, which is filtered-off and dried. After chromatography (hexane / ethyl acetate, 3 : 2) 258 g of the product 20 is obtained.
m: 147-148 C
P
d) 20 (258 mg; 0.75 mmole), RhC13-3H20 (19 mg, 0.075 mmole, 10 % mol) and p-toluene sulfonic acid (0.014 g, 0.075 mmole, 10 % mol) are placed in flask. Et0H (4.5 ml) and H20 (0.5 ml) are added and the mixture is refluxed for 3h. The mixture is evaporated to dryness, ethyl acetate added and then filtered over 5g of silica gel. The filtrate is evaporated. 235 mg of the product 21 is obtained.
\ s2 15 Second generation Grubb's catalyst 16 (Mes = mesityl, 140 mg, 0.166 mmole) and CuCI
(20mg, 0.20 mmole) are placed in Schlock's flask. CH2Cl2 (4 ml) is added under Argon and then a solution of 21(56 mg, 0.165 mmole) in CH2Cl2 (5 ml) is added. The solution is stirred at 40 C for 50 min under Argon. Thereafter, solvent is evaporated, ethyl acetate (ca. 10 ml) is added, white solid is filtered off and the filtrate is concentrated under 20 vacuum. The product is purified by column chromatography (15 %-30% ethyl acetate in cyclohexane). The product If (80 mg, 60 %) is obtained as a green solid.
Mes¨NN¨Mes Mes¨NN¨Mes CI I CI
10 (S2h Rtu¨
PCy, SO2 NO2 21 16 If Analogously to the processes described in the examples 1 to 7, the following compounds of formula 1c, Id, le, lg and lh are obtained. For instance, according to example 5 compound 12' is a ligand for complex 1c, compound 15 for complex Id or according to example 4 and 5 heptanone can be reacted with 11', oxidised and reacted with 16 to obtain complex le.
Mes-NN¨Mes = " Ru _ = t 0 POPh2 Mes-NNIrN¨Mes Ch, I
" Ru C _ = r". t 0 41 co Id Ch, I
" Ru _ = t le Mes-NNirN¨Mes Mes¨NN-Mes = " Ru_ __ RU õ
= t t CI
lg Mes-NNI/N¨Mes Cl /,I _ Ru _ Cr..- t ------c y 1 h Toluene is degassed by bubbling through nitrogen, 22 is dissolved in 10 ml of degassed toluene and added into the reaction flask. The solution is heated up to 80 C
and freshly prepared catalysts lc-h is added (1st) under nitrogen. After stirring for 60 min at the same to temperature the conversion is checked by HPLC. A second amount of catalysts 1c-h (2nd) is added under nitrogen and the conversion is checked 60 min later a second time by HPLC. Figure 1 is a graph comparing the cyclisation speed of 22. Table 1 shows the results of the HPLC analysis, wherein the catalyst 1c-h are compared with a known catalyst of formula 11 (Angew. Chem. Int. Ed. 2002, 41, 4038).
\ /1- sõCO2Me <rk A
4(CO2Me *:NH 0./NH
N Catalyst 1 b-h a -----0 ..:..
O
NH Nv c,., '-.._ II ,-S Br (:).,,,NH
b¨s 411 Br O
/---' Mes-NN-Mes CI, , I .
,Ru_ CI t I i Table 1 conversion [%Peak at 200nm]
catalyst 1st [mol%] 22 [mol] toluene [ml] 23 [60 min] 22 [60 min]
2nd [mol%] 23 [120 min] 22 [120 min]
1 c 0,4 0,0075 554 66,4 33,6 0,2 96,2 3,8 1d 0,4 0,0075 554 80,1 19,9 , 0,2 96,9 3,1 le 0,4 0,0075 554 89,9 10,1 0,2 98,9 1,1 1f (1st run) 0,4 0,0075 554 99,3 0,7 0,2 99,1 0,9 1f(2"d run) 0,4 0,0025 185 91,3 8,7 . 0,2 99,5 0,5 1 g 0,2 0,0075 554 - -0,1 98,8 1,2 1 h 0,4 0,0075 554 68,7 31,3 0,2 88,7 11,3 11(1st run) 0,4 0,0075 554 - -, 0,2 96,5 3,5 1i(2nd run) 0,4 0,015 1008 77,4 22,6 0,2 92,8 7,2 23.5 g Tetrakis hydroxy methyl phosphonium chloride (80%, 98.7 mmole) is dissolved in isopropanole (35 ml) under a nitrogen atmosphere. Then 12.1 g (98.7 mmole) of a 45%
KOH solution is added within 5 min while the solution is cooled (temperature 20-25 C).
After stirring the suspension for another 30 min under nitrogen, the mixture is filtered and the inorganic residue is washed with 20 ml of degassed isopropanole. The combined isopropanole solution is stored under a nitrogen atmosphere until use.
After cooling to 60 C 2.3 g (2.8 mmole) of the trihydroxy methyl phosphine (THP) solution is added to the reaction mixture of example 13. After stirring for 5 h at 60 C
the mixture is cooled to room temperature and extracted twice with 40 ml of degassed water, 40 ml of 0.5 M H CI, 40 ml of 0.5 M NaHCO3 solution, and 40 ml of water. Approx. 695 ml of toluene are distilled of at 50 C in vacuum (150 mbar) and the residue is treated at 50 C with 1.4 g of charcoal. The remaining liquid is added to 210 ml of pre-cooled methyl cyclohexane .(5 C). After stirring for further 60 min at 5 C the precipitate is filtered and washed with 100 ml of methyl cyclohexane (twice). The white solid is dried in vacuum at 30 C
to yield 23 as an almost white powder.
catalyst total yield % of 23 % of 22 1 c 96,2 86,02 1,20 Id 94,3 85,44 1,95
Claims (21)
1. A compound of formula 1, wherein:
XI and X2 are anionic ligands;
L1 is a neutral ligand;
R1 is -C1-20-alkyl, -C1-20-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl;
R3 is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl;
n is 0, 1, 2 or 3;
Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is -C1-20-alkyl or -C3-8-cycloalkyl, both optionally substituted by one or more groups that each independently are F, Cl, Br, I or -C1-6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are each independently -C1-20-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl; or R4, R5 and R6 are each independently a group of formula 1' wherein X1' and X2' are anionic ligands;
L1' is a neutral ligand;
R1' is -C1-20-alkyl, -C1-20-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2' is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl;
R3' is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
XI and X2 are anionic ligands;
L1 is a neutral ligand;
R1 is -C1-20-alkyl, -C1-20-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl;
R3 is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl;
n is 0, 1, 2 or 3;
Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is -C1-20-alkyl or -C3-8-cycloalkyl, both optionally substituted by one or more groups that each independently are F, Cl, Br, I or -C1-6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are each independently -C1-20-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl; or R4, R5 and R6 are each independently a group of formula 1' wherein X1' and X2' are anionic ligands;
L1' is a neutral ligand;
R1' is -C1-20-alkyl, -C1-20-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2' is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl;
R3' is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
2. A compound of formula 1, according to claim 1, wherein R4 is -C1-20-alkyl or -C3-8-cycloalkyl, both optionally substituted by one or more groups that each independently are F, CI, Br, I or -C1-6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups each independently are F, CI, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl, -SO2-aryl or a group of formula 1'; and R6 are each independently -C1-20-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl.
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl, -SO2-aryl or a group of formula 1'; and R6 are each independently -C1-20-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl.
3. A compound of formula 1, according to claim 1, wherein Z is -CO-R4 or -PO(R6)2; and R4 and R6 are a group of formula 1'.
4. A compound of formula 1, according to claim 1, wherein R1 is -C1-6-alkyl, -C1-6-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2 is H, -C1-6-alkyl, -C2-6-alkenyl, -C2-6-alkynyl or aryl;
R3 is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl;
Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is -C1-6-alkyl or -C3-8-cycloalkyl, both optionally substituted by one or more groups that each independently are F, CI, Br, I or -C1-6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are each independently -C1-6-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl; or R4, R5 and R6 are each independently a group of formula 1' wherein:
X1' and X2' are anionic ligands;
L1' is a neutral ligand;
R1' is -C1-6-alkyl, -C1-6-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2' is H, -C1-6-alkyl, -C2-6-alkynyl or aryl;
R3' is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
R2 is H, -C1-6-alkyl, -C2-6-alkenyl, -C2-6-alkynyl or aryl;
R3 is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl;
Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is -C1-6-alkyl or -C3-8-cycloalkyl, both optionally substituted by one or more groups that each independently are F, CI, Br, I or -C1-6-alkoxycarbonyl, or aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is -C1-8-fluoroalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C2-6-alkenyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are each independently -C1-6-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, CI, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl; or R4, R5 and R6 are each independently a group of formula 1' wherein:
X1' and X2' are anionic ligands;
L1' is a neutral ligand;
R1' is -C1-6-alkyl, -C1-6-haloalkyl, -C3-8-cycloalkyl or -C7-13-aralkyl;
R2' is H, -C1-6-alkyl, -C2-6-alkynyl or aryl;
R3' is -C1-6-alkyl, -C1-6-alkoxy, aryl, F or Cl; and n' is 0, 1, 2 or 3.
5. A compound of formula 1a, wherein X1, X2, L R1, R2, R3, n, and Z are as defined in claim 1.
6. A compound according to any one of claims 1-5, wherein X1 and X2 each independently are F, CI, Br or I.
7. A compound according to any one of claims 1-6, wherein X1 and X2 are Cl.
8. A compound according to claim 1, wherein Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is aryl or heteroaryl, both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -0CF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl, -SO2-aryl or a group of formula l'; and R6 are each independently -C1-6-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl.
R4 is aryl or heteroaryl both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3 or -C1-6-alkoxycarbonyl;
R5 is aryl or heteroaryl, both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -0CF3, -C1-6-alkoxycarbonyl, -SO2-C1-6-alkyl, -SO2-aryl or a group of formula l'; and R6 are each independently -C1-6-alkyl, -C3-8-cycloalkyl, aryl or heteroaryl, wherein aryl or heteroaryl are both optionally substituted by one or more groups that each independently are F, Cl, Br, I, -C1-6-alkyl, -C1-6-alkoxy, -NO2, -CN, -CF3, -OCF3, or -C1-6-alkoxycarbonyl.
9. A compound according to claim 1, wherein Z is -CO-R4, -SO2-R5 or -PO(R6)2;
R4 is aryl optionally substituted by one or more groups that each independently are F, -C1.6-alkoxy, -NO2 or -CF3;
R5 is aryl optionally substituted by one or more groups that each independently are F, -C1.6-alkoxy, -NO2, -CF3, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are aryl, both optionally substituted by one or more groups that each independently are F, -C1-6-alkoxy, -NO2 or -CF3.
R4 is aryl optionally substituted by one or more groups that each independently are F, -C1.6-alkoxy, -NO2 or -CF3;
R5 is aryl optionally substituted by one or more groups that each independently are F, -C1.6-alkoxy, -NO2, -CF3, -SO2-C1-6-alkyl or -SO2-aryl; and R6 are aryl, both optionally substituted by one or more groups that each independently are F, -C1-6-alkoxy, -NO2 or -CF3.
10. A compound according to any one of claims 1-9, wherein n is 0.
11. A compound according to any one of claim 1, wherein R1 is iso-propyl.
12. A compound according to any one of claims 1-11, wherein R2 is H or -CH3.
13. A compound according to any one of claims 1-12, wherein:
L1 is P(R11)3 or a ligand of formula 6a, 6b, 6c or 6d:
R11 is -C1-6-alkyl, -C3-8-cycloalkyl or aryl;
R7 and R8 are each independently H, -C1-20-alkyl, -C2-20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkoxy or halogen;
R9 and R10 are each independently H, -C1-20-alkyl, -C2-20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkyl, -C1-6-alkoxy or halogen; or R9 and R10 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring; and Y and Y' are halogen.
L1 is P(R11)3 or a ligand of formula 6a, 6b, 6c or 6d:
R11 is -C1-6-alkyl, -C3-8-cycloalkyl or aryl;
R7 and R8 are each independently H, -C1-20-alkyl, -C2-20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkoxy or halogen;
R9 and R10 are each independently H, -C1-20-alkyl, -C2-20-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkyl, -C1-6-alkoxy or halogen; or R9 and R10 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring; and Y and Y' are halogen.
14. A compound according to any one of claims 1-13, wherein:
L1 is P(R11)3 or a ligand of formula 6a, 6b, 6c or 6d:
R11 is -C1-6-alkyl, -C3-8-cycloalkyl or aryl;
R7and R8 are each independently H, -C1-6-alkyl, -C2-6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkyl, -C1-6-alkoxy or halogen;
R9 and R10 are each independently H, -C1-6-alkyl, -C2-6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkoxy or halogen; or R9 and R10 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring; and Y and Y' are halogen.
L1 is P(R11)3 or a ligand of formula 6a, 6b, 6c or 6d:
R11 is -C1-6-alkyl, -C3-8-cycloalkyl or aryl;
R7and R8 are each independently H, -C1-6-alkyl, -C2-6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkyl, -C1-6-alkoxy or halogen;
R9 and R10 are each independently H, -C1-6-alkyl, -C2-6-alkenyl or phenyl, wherein the phenyl is optionally substituted with up to three groups that independently are -C1-6-alkoxy or halogen; or R9 and R10 together with the carbon atoms to which they are attached are combined to form a carbocyclic 3 to 8 membered ring; and Y and Y' are halogen.
15. A compound according to claim 13 or 14, wherein L1 is a ligand of formula 6a, 6b, 6c or 6d, R7 and R8 are each independently tolyl, m-xylyl or mesityl; and R9 and R10 are each independently H or -C1-6-alkyl.
16. A compound according to any one of the claims 1-14, wherein:
L1 is P(R11)3; and R11 is phenyl or cyclohexyl.
L1 is P(R11)3; and R11 is phenyl or cyclohexyl.
17. A compound:
wherein Mes is mesityl, Ph is phenyl and p-CI-Ph is para-chlorphenyl.
wherein Mes is mesityl, Ph is phenyl and p-CI-Ph is para-chlorphenyl.
18. A
process for manufacturing a compound of formula 1 according to claim 1, said process comprising reacting a compound of formula 2:
wherein R1, R2, R3, n and Z are defined as in claim 1;
R12 is -C1-4-alkyl; and m is 0, 1 or 2;
with a ruthenium complex of formula 5 wherein X1, X2 and L1 are as defined in claim 1;
L2 is a neutral ligand, wherein L2 must not be the same group as L1 at the same time;
R13 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl.
process for manufacturing a compound of formula 1 according to claim 1, said process comprising reacting a compound of formula 2:
wherein R1, R2, R3, n and Z are defined as in claim 1;
R12 is -C1-4-alkyl; and m is 0, 1 or 2;
with a ruthenium complex of formula 5 wherein X1, X2 and L1 are as defined in claim 1;
L2 is a neutral ligand, wherein L2 must not be the same group as L1 at the same time;
R13 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl.
1 9. A
process for manufacturing a compound of formula la according to claim 5, said process comprising reacting a compound of formula 2a;
wherein R1, R2, R3, n and Z are defined as in claim 5;
R12 is -C1-4-alkyl; and m is 0, 1 or 2;
with a ruthenium complex of formula 5 wherein X1, X2 and L1 are as defined in claim 5;
L2 is a neutral ligand, wherein L2 must not be the same group then L1 at the same time;
R13 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl.
process for manufacturing a compound of formula la according to claim 5, said process comprising reacting a compound of formula 2a;
wherein R1, R2, R3, n and Z are defined as in claim 5;
R12 is -C1-4-alkyl; and m is 0, 1 or 2;
with a ruthenium complex of formula 5 wherein X1, X2 and L1 are as defined in claim 5;
L2 is a neutral ligand, wherein L2 must not be the same group then L1 at the same time;
R13 is H, -C1-20-alkyl, -C2-20-alkenyl, -C2-20-alkynyl or aryl; and R14 is aryl, vinyl or allenyl.
20. A process for carrying out a metathesis reaction, comprising contacting two compounds each having a C=C double bond, or one compound having at least two C=C
double bonds, with a catalyst, wherein the catalyst is the compound according to any one of claims 1-17.
double bonds, with a catalyst, wherein the catalyst is the compound according to any one of claims 1-17.
21. A process for carrying out a ring closing or cross metathesis reaction which process comprises contacting a dialkenyl compound with the compound according to claim 1.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03027828A EP1543875A1 (en) | 2003-12-04 | 2003-12-04 | Novel metathesis ruthenium catalyst |
| EP03027828.7 | 2003-12-04 | ||
| PCT/EP2004/013621 WO2005053843A1 (en) | 2003-12-04 | 2004-12-01 | Novel metathesis ruthenium catalyst |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2541514A1 CA2541514A1 (en) | 2005-06-16 |
| CA2541514C true CA2541514C (en) | 2013-07-09 |
Family
ID=34486115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2541514A Expired - Fee Related CA2541514C (en) | 2003-12-04 | 2004-12-01 | Novel metathesis ruthenium catalyst |
Country Status (4)
| Country | Link |
|---|---|
| EP (2) | EP1543875A1 (en) |
| JP (1) | JP4785748B2 (en) |
| CA (1) | CA2541514C (en) |
| WO (1) | WO2005053843A1 (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003044060A2 (en) | 2001-11-15 | 2003-05-30 | Materia, Inc. | Chelating carbene ligand precursors and their use in the synthesis of metathesis catalysts |
| US7176208B2 (en) | 2003-04-18 | 2007-02-13 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors |
| DE102004033312A1 (en) * | 2004-07-08 | 2006-01-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Continuous metathesis process with ruthenium catalysts |
| EP2886549A1 (en) * | 2005-07-04 | 2015-06-24 | Zannan Scitech Co., Ltd. | Ruthenium complex ligand, ruthenium complex and the use of the complex as a catalyst in olefin metathesis reactions |
| ATE480216T1 (en) | 2006-02-02 | 2010-09-15 | 3M Innovative Properties Co | SOLIDS OBTAINED THROUGH ROMP |
| EP1942125A1 (en) | 2006-12-20 | 2008-07-09 | 3M Innovative Properties Company | Compositions curable by ring opening metathesis polymerarization at low temperatures and their application in the dental field |
| DE102007020694A1 (en) * | 2007-05-03 | 2008-11-06 | Evonik Degussa Gmbh | Sulfur-containing metathesis catalysts |
| WO2010090976A1 (en) | 2009-02-03 | 2010-08-12 | Idenix Pharmaceuticals, Inc. | Phosphinate ruthenium complexes |
| TW201040181A (en) | 2009-04-08 | 2010-11-16 | Idenix Pharmaceuticals Inc | Macrocyclic serine protease inhibitors |
| SG175334A1 (en) * | 2009-05-07 | 2011-11-28 | Hoffmann La Roche | Process for the preparation of ruthenium metathesis complex catalysts |
| EP2461811B1 (en) | 2009-08-05 | 2016-04-20 | Idenix Pharmaceuticals LLC. | Macrocyclic serine protease inhibitors useful against viral infections, particularly hcv |
| WO2011079439A1 (en) * | 2009-12-30 | 2011-07-07 | Zannan Scitech Co., Ltd. | Highly active metathesis catalysts selective for romp and rcm reactions |
| WO2012109398A1 (en) | 2011-02-10 | 2012-08-16 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors, pharmaceutical compositions thereof, and their use for treating hcv infections |
| EP2826802B1 (en) | 2012-03-16 | 2021-03-10 | Zeon Corporation | Method for producing ring-opening metathesis polymer hydride, and resin composition |
| HUE028176T2 (en) | 2012-06-29 | 2016-12-28 | Apeiron Synthesis Sa | Metal complexes, their application and methods of carrying out of metathesis reaction |
| WO2019110658A1 (en) * | 2017-12-08 | 2019-06-13 | Arlanxeo Deutschland Gmbh | Process for producing nitrile rubbers using ruthenium complex catalysts |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5334716A (en) * | 1991-06-17 | 1994-08-02 | Fujisawa Pharmaceutical Co., Ltd. | Heterocyclic derivatives |
| WO2001083097A2 (en) * | 2000-05-04 | 2001-11-08 | University Of Florida | Metathesis of functionalized allylic olefins |
| AU2001284773B2 (en) * | 2000-08-10 | 2004-08-05 | Trustees Of Boston College | Recyclable metathesis catalysts |
| DE10137051A1 (en) * | 2001-07-31 | 2003-02-20 | Bayer Ag | New transition metal complexes with 2-alkoxybenzylidene ligands and hydrogenated imidazole ligands, useful as catalysts in metathesis reactions |
| PL199412B1 (en) * | 2002-10-15 | 2008-09-30 | Boehringer Ingelheim Int | Ruthenium new complexes as (pre) catalytic agents of permutation reaction, new derivatives of 2-alkoxy-5-nitrostyrene as intermediate compounds and method of their receiving |
-
2003
- 2003-12-04 EP EP03027828A patent/EP1543875A1/en not_active Withdrawn
-
2004
- 2004-12-01 EP EP04803392.2A patent/EP1827688B1/en not_active Expired - Lifetime
- 2004-12-01 JP JP2006541877A patent/JP4785748B2/en not_active Expired - Fee Related
- 2004-12-01 WO PCT/EP2004/013621 patent/WO2005053843A1/en active Application Filing
- 2004-12-01 CA CA2541514A patent/CA2541514C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007534640A (en) | 2007-11-29 |
| WO2005053843A1 (en) | 2005-06-16 |
| JP4785748B2 (en) | 2011-10-05 |
| CA2541514A1 (en) | 2005-06-16 |
| EP1543875A1 (en) | 2005-06-22 |
| EP1827688B1 (en) | 2014-09-03 |
| EP1827688A1 (en) | 2007-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2541514C (en) | Novel metathesis ruthenium catalyst | |
| CA2502342C (en) | Ruthenium complexes as (pre)catalysts for metathesis reactions | |
| JP5993104B2 (en) | Catalytic complexes with carbene ligands | |
| JP5522941B2 (en) | Process for the production of organometallic ruthenium complexes and related tetrasubstituted and other bulky olefins | |
| JP5787751B2 (en) | Method for producing a ruthenium carbene complex | |
| JP5619724B2 (en) | Ruthenium olefin metathesis catalyst having N-heterocyclic carbene ligand with substituted skeleton | |
| Erker et al. | Reactions of. beta.-CH agostic alkenylzirconocene complexes | |
| US7109344B2 (en) | Ruthenium catalyst | |
| JP6395714B2 (en) | Ruthenium-based metathesis catalysts, precursors for their production and their use | |
| CA2478482A1 (en) | Metalorganic catalysts for chemo-, regio- and stereoselective reactions, and corresponding precursors | |
| JP2004536153A (en) | Novel transition metal complexes and their use in transition metal-catalyzed reactions | |
| US5929265A (en) | Binuclear iridium(I) phosphine complexes and their use as catalyst in the asymmetric hydroamination of olefins | |
| WO2011156921A2 (en) | Catalyst ligands, catalytic ligand complexes and polymerization processes using same | |
| WO2011056884A2 (en) | Carbene complexes of lithium and/or magnesium metal salts, and uses thereof | |
| WO2016100101A1 (en) | Ruthenium-based metathesis pre-catalyst compounds | |
| JP2015063511A (en) | Phosphorus compounds and their transition metal complexes | |
| JP4413507B2 (en) | Pincer metal complex, method for producing the same, and pincer metal complex catalyst | |
| Choi et al. | Formation of thioruthenium carbonyl clusters via a thioallyl cation complex | |
| Wheals | Group 8 transition metal complexes bearing donor-functionalised NHC ligands | |
| Ma | Synthesis and Characterization of Ligands and Transition Metal Complexes Containing M-Terphenyl Scaffolds | |
| Tapu | New architectures in imidazol-2-ylidene chemistry | |
| Koo | Synthesis of New Ruthenium Complexes for Propargylic Substitution Reactions | |
| Serre | Synthesis of new N-heterocyclic carbene metal complexes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20161201 |