DE102011054477A1 - Process for the catalytic heteroaromatic hydrogenation - Google Patents

Abstract

The present invention describes a novel ruthenium catalyst for the selective hydrogenation of heteroaromatics, wherein the ruthenium catalyst comprises an N-heterocyclic carbene ligand. For chiral ligands asymmetric synthesis is also possible.

Description

The present invention relates to a process for the catalytic heteroaromatic hydrogenation. Hydrogenation processes and suitable catalysts for this are constantly the subject of research, however, only a few catalysts are known from the prior art, which can be used specifically for heteroaromatic hydrogenation, in particular in benzanelated heteroaromatics.

Thus, there is a continuing need for alternative and novel hydrogenation processes and catalysts for carrying out these processes.

It is thus an object of the present invention to provide a process for the hydrogenation of heteroaromatics and a catalyst therefor. This object is achieved by a catalyst according to claim 1 and a method according to claim 7.

Accordingly, there is provided a catalyst for the hydrogenation of heteroaromatics comprising at least one ruthenium atom and at least one N-heterocyclic carbene ligand.

• a) Reduktion des Heteroaromaten mit einem Katalysator, umfassend mindestens ein Rutheniumatom sowie mindestens einen N-Heterocyclischen Carbenliganden, in Gegenwart eines Reduktionsmittels

Further provided is a process for the hydrogenation of heteroaromatics comprising the step

• a) reduction of the heteroaromatic with a catalyst comprising at least one ruthenium atom and at least one N-heterocyclic carbene ligand, in the presence of a reducing agent

Surprisingly, it has been found that such catalysts are suitable for the hydrogenation of heteroaromatics. Particularly reactive heteroaromatics are:

1.) Aromatic compounds containing five-membered aromatic rings having at least one heteroatom

Aromatic compounds contain five-membered aromatics having at least one heteroatom i. In particular (but not limited to) compounds containing a furan, thiophene or pyrrole ring are particularly reactive compounds. It has been found that with benzene-ligated compounds, i. such as (but not limited to) benzofuran or indole specifically only the heteroaromatic ring is hydrogenated, the aromatic ring remains intact. This is surprising since hydrogenation processes for the targeted hydrogenation of the "heteroaromatic part" of these compounds are extremely rare.

Thus, the present invention more particularly relates to a catalyst and a hydrogenation process for the hydrogenation of aromatic compounds comprising a heterocyclic five-membered aromatic.

2.) Aromatic compounds containing six-membered aromatic ring with a heteroatom

Aromatic compounds comprising a six-membered aromatic having at least one heteroatom have also been found to be reactive compounds. Thus, the present invention more particularly relates to a catalyst and a hydrogenation process for the hydrogenation of aromatic compounds comprising a six-membered aromatic having at least one heteroatom.

However, in practice, in some classes of applications, this class of compounds has been shown to hydrogenate, partially or even predominantly, the non-heterocyclic ring (benzene ring) in benzene-based compounds (such as quinoxalines) depending on the specific reaction conditions; this must be taken into account in practice.

If the heteroatom is both part of a five-membered ring and a six-membered ring (as in indolizine), it has been found that most of the six-membered ring is preferably hydrogenated.

The term "hydrogenation" is understood in particular to mean that in total two hydrogens are added to a "double bond" of the heterocycle. However, the present invention is not limited to hydrogen as a concrete reducing agent, although it is a preferred embodiment of the invention (as described below).

The term "N-heterocyclic carbene ligand" is understood to mean electron-rich, nucleophilic compounds of divalent carbon species with electron sequets, such as, for example, Imidazolylidenes, imidazolidinylidenes and triazolylidenes.

It should be noted that according to the present invention, the actual reactive catalyst does not have to be used in substance, but can also be prepared in situ from suitable precursors; this will be explained below.

• a0) in situ Synthese des Katalysators aus geeigneten Vorstufen

Thus, according to a preferred embodiment, the method according to the invention comprises the step a0), which is carried out before a):

• a0) in situ synthesis of the catalyst from suitable precursors

This can be done by using a sufficiently labile ruthenium complex (eg Ru (cod) (2-methylallyl) ₂ or other suitable complexes) and a salt derivative of the N-heterocyclic carbene in the presence of a strong base.

wobei

R¹ oder R² entweder ein substituierter oder unsubstituierter Kohlenstoff oder ein Stickstoff sein können (wobei aber R¹ und R² nicht beide Stickstoff sind), wobei die Substitutionen ausgewählt sind aus (unabhängig voneinander) Alkyl, langkettiges Alkyl, Alkoxy, langkettiges Alkoxy, Cycloalkyl, Halogenalkyl, Aryl, Halogenaryl, Heteroaryl, Heterocycloalkylene, Heterocycloalkyl, Halogenheteroaryl, Alkenyl, Halogenalkenyl, Alkinyl, Halogenalkinyl, Ketoaryl, Halogenketoaryl, Ketoheteroaryl, Ketoalkyl, Halogenketoalkyl, Silylalkyl, Silylalkyloxy sei könen, wobei bei geeigneten Resten eine oder mehrere nicht-benachbarte CH₂-Gruppen unabhängig voneinander durch -O-, -S-, -NH-, -NR°-, -SiR°R°°-, -CO-, -COO-, -OCO-, -OCO-O-, -SO₂-, -S-CO-, -CO-S-, -CY¹=CY² oder -C≡C- ersetzt sein können und zwar derart, dass O und/oder S Atome nicht direkt miteinander verbunden sind, ebenfalls optional mit Aryl- oder Heteroaryl bevorzugt enthaltend 1 bis 30 C Atome ersetzt sind (endständige CH₃-Gruppen werden wie CH₂-Gruppen im Sinne von CH₂-H verstanden.)

R³ und R⁴ unabhängig voneinander Alkyl, langkettiges Alkyl, Alkoxy, langkettiges Alkoxy, Cycloalkyl, Halogenalkyl, Aryl, Halogenaryl, Heteroaryl, Heterocycloalkylene, Heterocycloalkyl, Halogenheteroaryl, Alkenyl, Halogenalkenyl, Alkinyl, Halogenalkinyl, Ketoaryl, Halogenketoaryl, Ketoheteroaryl, Ketoalkyl, Halogenketoalkyl, Silylalkyl, Silylalkyloxy sei können, wobei bei geeigneten Resten eine oder mehrere nicht-benachbarte CH₂-Gruppen unabhängig voneinander durch -O-, -S-, -NH-, -NR°-, -SiR°R°°-, -CO-, -COO-, -OCO-, -OCO-O-, -SO₂-, -S-CO-, -CO-S-, -CY¹=CY² oder -C≡C- ersetzt sein können und zwar derart, dass O und/oder S Atome nicht direkt miteinander verbunden sind, ebenfalls optional mit Aryl- oder Heteroaryl bevorzugt enthaltend 1 bis 30 C Atome ersetzt sind (endständige CH₃-Gruppen werden wie CH₂-Gruppen im Sinne von CH₂-H verstanden.)

wobei die Bindung zwischen R¹ und R² eine Einfach- oder Doppelbindung sein kann

und R¹ und R³ einerseits und/oder R² und R⁴ anderseits so substituiert sein können, dass sich zwischen R¹ und R³ bzw. R² und R⁴ ein Ring bildet.

allgemeine Gruppendefinition: Innerhalb der Beschreibung und den Ansprüchen werden allgemeine Gruppen, wie z.B: Alkyl, Alkoxy, Aryl etc. beansprucht und beschrieben. Wenn nicht anders beschrieben, werden bevorzugt die folgenden Gruppen innerhalb der allgemein beschriebenen Gruppen im Rahmen der vorliegenden Erfindung verwendet:

alkyl: lineare und verzweigte C1-C8-Alkyle,

langkettige Alkyle: lineare und verzweigte C5-C20 Alkyle

alkenyl: C2-C6-alkenyl,

cycloalkyl: C3-C8-cycloalkyl,

alkoxy: C1-C6-alkoxy,

langkettig Alkoxy: lineare und verzweigte C5-C20 Alkoxy

alkylene: ausgewählt aus der Gruppe enthaltend: methylene; 1,1-ethylene; 1,2-ethylene; 1,1-propylidene; 1,2-propylene; 1,3-propylene; 2,2-propylidene; butan-2-ol-1,4-diyl; propan-2-ol-1,3-diyl; 1,4-butylene; cyclohexane-1,1-diyl; cyclohexan-1,2-diyl; cyclohexan-1,3-diyl; cyclohexan-1,4-diyl; cyclopentane-1,1-diyl; cyclopentan-1,2-diyl; und cyclopentan-1,3-diyl,

aryl: ausgewählt aus Aromaten mit einem Molekulargewicht unter 300Da

arylene: ausgewählt aus der Gruppe enthaltend: 1,2-phenylene; 1,3-phenylene; 1,4-phenylene; 1,2-naphtalenylene; 1,3-naphtalenylene; 1,4-naphtalenylene; 2,3-naphtalenylene; 1-hydroxy-2,3-phenylene; 1-hydroxy-2,4-phenylene; 1-hydroxy-2,5-phenylene; und 1-hydroxy-2,6-phenylene,

heteroaryl: ausgewählt aus der Gruppe enthaltend: pyridinyl; pyrimidinyl; pyrazinyl; triazolyl; pyridazinyl; 1,3,5-triazinyl; chinoninyl; isochinoninyl; chinoxalinyl; imidazolyl; pyrazolyl; benzimidazolyl; thiazolyl; oxazolidinyl; pyrrolyl; thiophenyl; carbazolyl; indolyl; und isoindolyl, wobei das Heteroaryl mit der Verbindung über jedes Atom im Ring des ausgewählten Heteroaryls verbunden sein kann.

heteroarylene: ausgewählt aus der Gruppe enthaltend: pyridindiyl; quinolindiyl; pyrazodiyl; pyrazoldiyl; triazolediyl; pyrazindiyl, thiophendiyl; und imidazolediyl, wobei das heteroarylene als Brücke in der Verbindung über ein beliebiges Atom im Ring des ausgewählten Heteroaryls fungiert, speziell bevorzugt sind: pyridin-2,3-diyl; pyridin-2,4-diyl; pyridin-2,5-diyl; pyridin-2,6-diyl; pyridin-3,4-diyl; pyridin-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; quinolin-2,8-diyl; isoquinolin-1,3-diyl; isoquinolin-1,4-diyl; pyrazol-1,3-diyl; pyrazol-3,5-diyl; triazole-3,5-diyl; triazole-1,3-diyl; pyrazin-2,5-diyl; und imidazole-2,4-diyl, thiophen-2,5-diyl, thiophen-3,5-diyl; ein -C1-C6-heterocycloalkyl, ausgewählt aus der Gruppe enthaltend: piperidinyl; piperidine; 1,4-piperazine, tetrahydrothiophene; tetrahydrofuran; 1,4,7-triazacyclononane; 1,4,8,11-tetraazacyclotetradecane; 1,4,7,10,13-pentaazacyclopentadecane; 1,4-diaza-7-thia-cyclononane; 1,4-diaza-7-oxa-cyclononane; 1,4,7,10-tetraazacyclododecane; 1,4-dioxane; 1,4,7-trithia-cyclononane; pyrrolidine; und tetrahydropyran, wobei das Heteroaryl mit dem C1-C6-Alkyl über jedes Atom im Ring des ausgewählten Heteroaryls verbunden sein kann.

heterocycloalkylene: ausgewählt aus der Gruppe enthaltend: piperidin-1,2-ylene; piperidin-2,6-ylene; piperidin-4,4-ylidene; 1,4-piperazin-1,4-ylene; 1,4-piperazin-2,3-ylene; 1,4-piperazin-2,5-ylene; 1,4-piperazin-2,6-ylene; 1,4-piperazin-1,2-ylene; 1,4-piperazin-1,3-ylene; 1,4-piperazin-1,4-ylene; tetrahydrothiophen-2,5-ylene; tetrahydrothiophen-3,4-ylene; tetrahydrothiophen-2,3-ylene; tetrahydrofuran-2,5-ylene; tetrahydrofuran-3,4-ylene; tetrahydrofuran-2,3-ylene; pyrrolidin-2,5-ylene; pyrrolidin-3,4-ylene; pyrrolidin-2,3-ylene; pyrrolidin-1,2-ylene; pyrrolidin-1,3-ylene; pyrrolidin-2,2-ylidene; 1,4,7-triazacyclonon-1,4-ylene; 1,4,7-triazacyclonon-2,3-ylene; 1,4,7-triazacyclonon-2,9-ylene; 1,4,7-triazacyclonon-3,8-ylene; 1,4,7-triazacyclonon-2,2-ylidene; 1,4,8,11-tetraazacyclotetradec-1,4-ylene; 1,4,8,11-tetraazacyclotetradec-1,8-ylene; 1,4,8,11-tetraazacyclotetradec-2,3-ylene; 1,4,8,11-tetraazacyclotetradec-2,5-ylene; 1,4,8,11-tetraazacyclotetradec-1,2-ylene; 1,4,8,11-tetraazacyclotetradec-2,2-ylidene; 1,4,7,10-tetraazacyclododec-1,4-ylene; 1,4,7,10-tetraazacyclododec-1,7-ylene; 1,4,7,10-tetraazacyclododec-1,2-ylene; 1,4,7,10-tetraazacyclododec-2,3-ylene; 1,4,7,10-tetraazacyclododec-2,2-ylidene; 1,4,7,10,13-pentaazacyclopentadec-1,4-ylene; 1,4,7,10,13-pentaazacyclopentadec-1,7-ylene; 1,4,7,10,13-pentaazacyclopentadec-2,3-ylene; 1,4,7,10,13-pentaazacyclopentadec-1,2-ylene; 1,4,7,10,13-pentaazacyclopentadec-2,2-ylidene; 1,4-diaza-7-thia-cyclonon-1,4-ylene; 1,4-diaza-7-thia-cyclonon-1,2-ylene; 1,4-diaza-7thia-cyclonon-2,3-ylene; 1,4-diaza-7-thia-cyclonon-6,8-ylene; 1,4-diaza-7-thia-cyclonon-2,2-ylidene; 1,4-diaza-7-oxacyclonon-1,4-ylene; 1,4-diaza-7-oxa-cyclonon-1,2-ylene; 1,4diaza-7-oxa-cyclonon-2,3-ylene; 1,4-diaza-7-oxa-cyclonon-6, 8-ylene; 1,4-diaza-7-oxa-cyclonon-2,2-ylidene; 1,4-dioxan-2,3-ylene; 1,4-dioxan-2,6-ylene; 1,4-dioxan-2,2-ylidene; tetrahydropyran-2,3-ylene; tetrahydropyran-2,6-ylene; tetrahydropyran-2,5-ylene; tetrahydropyran-2,2-ylidene; 1,4,7-trithia-cyclonon-2,3-ylene; 1,4,7-trithia-cyclonon-2,9-ylene; und 1,4,7-trithia-cyclonon-2,2-ylidene,

heterocycloalkyl: ausgewählt aus der Gruppe enthaltend: pyrrolinyl; pyrrolidinyl; morpholinyl; piperidinyl; piperazinyl; hexamethylene imine; 1,4-piperazinyl; tetrahydrothiophenyl; tetrahydrofuranyl; 1,4,7-triazacyclononanyl; 1,4,8,11-tetraazacyclotetradecanyl; 1,4,7,10,13-pentaazacyclopentadecanyl; 1,4-diaza-7-thiacyclononanyl; 1,4-diaza-7-oxa-cyclononanyl; 1,4,7,10-tetraazacyclododecanyl; 1,4-dioxanyl; 1,4,7-trithiacyclononanyl; tetrahydropyranyl; und oxazolidinyl, wobei das Heterocycloalkyl mit der Verbindung über jedes Atom im Ring des ausgewählten Heterocycloalkyls verbunden sein kann.

amine: die Gruppe -N(R)2 wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1-C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildet

halogen: ausgewählt aus der Gruppe enthaltend: F; Cl; Br und I,

halogenalkyl: ausgewählt aus der Gruppe enthaltend mono, di, tri-, poly und perhalogenated lineare und verzweigte C1-C8-alkyl

pseudohalogen: ausgewählt aus der Gruppe enthaltend -CN, -SCN, -OCN, N3, -CNO, -SeCN

sulphonate: die Gruppe -S(O)2OR, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; Na; K; Cs; Mg; und Ca,

sulphate: die Gruppe -OS(O)2OR, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; Na; K; Cs; Mg; und Ca,

sulphone: die Gruppe -S(O)2R, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 und amine (to give sulphonamide) ausgewählt aus der Gruppe: -NR'2, wobei jedes R’ unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildet

carboxylat: die Gruppe -C(O)OR, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; Na; K; Cs; Mg; und Ca,

carbonyl: die Gruppe -C(O)R, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 und amine (to give amide) ausgewählt aus der Gruppe: -NR'2, wobei jedes R’ unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1-C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildet

phosphonate: die Gruppe -P(O) (OR) 2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; Na; K; Cs; Mg; und Ca,

phosphate: die Gruppe -OP(O)(OR)2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; Na; K; Cs; Mg; und Ca,

phosphine: die Gruppe -P(R)2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; und C1-C6-alkyl-C6H5,

phosphine oxid: die Gruppe -P(O)R2, wobei R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; und C1-C6-alkyl-C6H5; und amine (to give phosphonamidate) ausgewählt aus der Gruppe: -NR'2, wobei jedes R' unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1-C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildet.

polyether: ausgewählt aus der Gruppe enthaltend -(O-CH₂-CH(R))_n-OH und -(O-CH₂-CH(R))_n-H wobei R unabhängig ausgewählt ist aus: Wasserstoff, alkyl, aryl, halogen und n ist von 1 to 250

silylalkyl: die Gruppe -SiR₃, wobei jedes R unabhängig voneinander ausgewählt ist aus: Wasserstoff; C1-C6- alkyl; phenyl; C1-C6-alkyl-C6H5 und amine (to give sulphonamide) ausgewählt aus der Gruppe: -NR'2, wobei jedes R’ unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildet

silylalkyloxy: die Gruppe -OSiR₃, wobei jedes R unabhängig voneinander ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 und amine (to give sulphonamide) ausgewählt aus der Gruppe: -NR'2, wobei jedes R’ unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; C1C6-alkyl-C6H5; und phenyl, wobei wenn beide R’ C1-C6 alkyl sind, beide R’ einen -NC3 bis NC5 heterocyclischen Ring bilden können, wobei die restliche Alkylkette einen Alkylsubstituenten am heterocyclischen Ring bildetAccording to a preferred embodiment of the invention, the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:

in which

R ¹ or R ² may be either a substituted or unsubstituted carbon or a nitrogen (but R ¹ and R ^{2 are} not both nitrogen), where the substitutions are selected from (independently of one another) alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, Cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, halo-heteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals include one or more non-adjacent ones CH ₂ groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal GE CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H.)

R ³ and R ⁴ are each independently alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, halo heteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, halo-ketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl Silylalkyl, silylalkyloxy, where, with suitable radicals, one or more non-adjacent CH ₂ groups are independently of one another denoted by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, - CO, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- may be replaced and Although in such a way that O and / or S atoms are not directly connected to one another, they are also optionally replaced by aryl or heteroaryl preferably containing 1 to 30 C atoms (terminal CH ₃ groups are the same as CH ₂ groups in the sense of CH ₂ - H understood.)

wherein the bond between R ¹ and R ^{2 may be} a single or double bond

and R ¹ and R ³ on the one hand and / or R ² and R ⁴ on the other hand can be substituted so that between R ¹ and R ³ or R ² and R ^{4 forms} a ring.

General Group Definition: Within the specification and claims, general groups such as: alkyl, alkoxy, aryl, etc. are claimed and described. Unless otherwise described, the following groups are preferably used within the groups generally described in the context of the present invention:

alkyl: linear and branched C1-C8-alkyls,

long-chain alkyls: linear and branched C5-C20 alkyls

alkenyl: C2-C6 alkenyl,

cycloalkyl: C3-C8-cycloalkyl,

alkoxy: C 1 -C 6 -alkoxy,

long-chain alkoxy: linear and branched C5-C20 alkoxy

alkylene: selected from the group comprising: methylene; 1,1-ethylene; 1,2-ethylene; 1,1-propylidene; 1,2-propylene; 1,3-propylene; 2,2-propylidene; butan-2-ol-1,4-diyl; propan-2-ol-1,3-diyl; 1,4-butylene; cyclohexane-1,1-diyl; cyclohexane-1,2-diyl; cyclohexane-1,3-diyl; cyclohexane-1,4-diyl; cyclopentane-1,1-diyl; cyclopentane-1,2-diyl; and cyclopentane-1,3-diyl,

aryl: selected from aromatics having a molecular weight below 300Da

arylenes: selected from the group comprising: 1,2-phenylenes; 1,3-phenylene; 1,4-phenylene; 1,2-naphtalenylene; 1,3-naphtalenylene; 1,4-naphtalenylene; 2,3-naphtalenylene; 1-hydroxy-2,3-phenylene; 1-hydroxy-2,4-phenylene; 1-hydroxy-2,5-phenylene; and 1-hydroxy-2,6-phenylenes,

heteroaryl: selected from the group comprising: pyridinyl; pyrimidinyl; pyrazinyl; triazolyl; pyridazinyl; 1,3,5-triazinyl; chinoninyl; isochinoninyl; quinoxalinyl; imidazolyl; pyrazolyl; benzimidazolyl; thiazolyl; oxazolidinyl; pyrrolyl; thiophenyl; carbazolyl; indolyl; and isoindolyl, wherein the heteroaryl may be linked to the compound via any atom in the ring of the selected heteroaryl.

heteroarylenes: selected from the group comprising: pyridinediyl; quinolindiyl; pyrazodiyl; pyrazoldiyl; triazolediyl; pyrazinediyl, thiophenediyl; and imidazolediyl, wherein the heteroarylene acts as a bridge in the compound via any atom in the ring of the selected heteroaryl, especially preferred are: pyridine-2,3-diyl; pyridin-2,4-diyl; pyridin-2,5-diyl; pyridin-2,6-diyl; pyridin-3,4-diyl; pyridine-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; quinolin-2,8-diyl; isoquinolin-1,3-diyl; isoquinolin-1,4-diyl; pyrazol-1,3-diyl; pyrazol-3,5-diyl; triazole-3,5-diyl; triazole-1,3-diyl; pyrazin-2,5-diyl; and imidazole-2,4-diyl, thiophene-2,5-diyl, thiophene-3,5-diyl; a C1-C6 heterocycloalkyl selected from the group comprising: piperidinyl; piperidines; 1,4-piperazines, tetrahydrothiophenes; tetrahydrofuran; 1,4,7-triazacyclononanes; 1,4,8,11-tetraazacyclotetradecane; 1,4,7,10,13-pentaazacyclopentadecane; 1,4-diaza-7-thia-cyclononane; 1,4-diaza-7-oxa-cyclononane; 1,4,7,10-tetraazacyclododecanes; 1,4-dioxane; 1,4,7-trithia-cyclononane; pyrrolidine; and tetrahydropyran, wherein the heteroaryl may be joined to the C1-C6 alkyl via any atom in the ring of the selected heteroaryl.

heterocycloalkylenes: selected from the group comprising: piperidin-1,2-ylene; piperidin-2,6-ylene; piperidin-4,4-ylidene; 1,4-piperazin-1,4-ylene; 1,4-piperazin-2,3-ylene; 1,4-piperazin-2,5-ylene; 1,4-piperazin-2,6-ylene; 1,4-piperazin-1,2-ylene; 1,4-piperazin-1,3-ylene; 1,4-piperazin-1,4-ylene; tetrahydrothiophen-2,5-ylene; tetrahydrothiophen-3,4-ylene; tetrahydrothiophen-2,3-ylene; tetrahydrofuran-2,5-ylene; tetrahydrofuran-3,4-ylene; tetrahydrofuran-2,3-ylene; pyrrolidin-2,5-ylene; pyrrolidin-3,4-ylene; pyrrolidin-2,3-ylene; pyrrolidin-1,2-ylene; pyrrolidin-1,3-ylene; pyrrolidin-2,2-ylidene; 1,4,7-triazacyclonon-1,4-ylene; 1,4,7-triazacyclonon-2,3-ylene; 1,4,7-triazacyclonon-2,9-ylene; 1,4,7-triazacyclonon-3,8-ylene; 1,4,7-triazacyclonon-2,2-ylidene; 1,4,8,11-tetraazacyclotetradec-1,4-ylene; 1,4,8,11-tetraazacyclotetradec-1,8-ylene; 1,4,8,11-tetraazacyclotetradec-2,3-ylene; 1,4,8,11-tetraazacyclotetradec-2,5-ylene; 1,4,8,11-tetraazacyclotetradec-1,2-ylene; 1,4,8,11-tetraazacyclotetradec-2,2-ylidene; 1,4,7,10-tetraazacyclododec-1,4-ylene; 1,4,7,10-tetraazacyclododec-1,7-ylene; 1,4,7,10-tetraazacyclododec-1,2-ylene; 1,4,7,10-tetraazacyclododec-2,3-ylene; 1,4,7,10-tetraazacyclododec-2,2-ylidene; 1,4,7,10,13-pentaazacyclopentadec-1,4-ylene; 1,4,7,10,13-pentaazacyclopentadec-1,7-ylene; 1,4,7,10,13-pentaazacyclopentadec-2,3-ylene; 1,4,7,10,13-pentaazacyclopentadec-1,2-ylene; 1,4,7,10,13-pentaazacyclopentadec-2,2-ylidene; 1,4-diaza-7-thia-cyclonon-1,4-ylene; 1,4-diaza-7-thia-cyclonon-1,2-ylene; 1,4-diaza-7thia-cyclonon-2,3-ylene; 1,4-diaza-7-thia-cyclonon-6,8-ylene; 1,4-diaza-7-thia-cyclonon-2,2-ylidene; 1,4-diaza-7-oxacyclonon-1,4-ylene; 1,4-diaza-7-oxa-cyclonon-1,2-ylene; 1,4diaza-7-oxa-cyclonon-2,3-ylene; 1,4-diaza-7-oxa-cyclonone-6,8-ylene; 1,4-diaza-7-oxa-cyclonon-2,2-ylidene; 1,4-dioxan-2,3-ylene; 1,4-dioxan-2,6-ylene; 1,4-dioxan-2,2-ylidene; tetrahydropyran-2,3-ylene; tetrahydropyran-2,6-ylene; tetrahydropyran-2,5-ylene; tetrahydropyran-2,2-ylidene; 1,4,7-trithia-cyclonon-2,3-ylene; 1,4,7-trithia-cyclonon-2,9-ylene; and 1,4,7-trithia-cyclonone-2,2-ylidenes,

heterocycloalkyl: selected from the group comprising: pyrrolinyl; pyrrolidinyl; morpholinyl; piperidinyl; piperazinyl; hexamethylene imine; 1,4-piperazinyl; tetrahydrothiophenyl; tetrahydrofuranyl; 1,4,7-triazacyclononanyl; 1,4,8,11-tetraazacyclotetradecanyl; 1,4,7,10,13-pentaazacyclopentadecanyl; 1,4-diaza-7-thiacyclononanyl; 1,4-diaza-7-oxa-cyclononanyl; 1,4,7,10-tetraazacyclododecanyl; 1,4-dioxanyl; 1,4,7-trithiacyclononanyl; tetrahydropyranyl; and oxazolidinyl, wherein the heterocycloalkyl may be linked to the compound via any atom in the ring of the selected heterocycloalkyl.

amine: the group -N (R) 2 wherein each R is independently selected from: hydrogen; C1-C6-alkyl; C1-C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring

halogen: selected from the group comprising: F; Cl; Br and I,

haloalkyl: selected from the group consisting of mono, di, tri, poly and perhalogenated linear and branched C1-C8-alkyl

pseudohalogen: selected from the group consisting of -CN, -SCN, -OCN, N3, -CNO, -SeCN

sulphonates: the group -S (O) 2OR, where R is selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca,

sulphate: the group -OS (O) 2OR, where R is selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca,

sulphone: the group -S (O) 2 R, wherein R is selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 and amine (to give sulphonamide) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; C1C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring

carboxylate: the group -C (O) OR, wherein R is selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca,

carbonyl: the group -C (O) R, wherein R is selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 and amine (to give amide) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; C1-C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring

phosphonates: the group -P (O) (OR) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca,

phosphates: the group -OP (O) (OR) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca,

phosphines: the group -P (R) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; and C1-C6-alkyl-C6H5,

phosphine oxide: the group -P (O) R2, wherein R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; and C1-C6-alkyl-C6H5; and amines (to give phosphonamidate) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; C1-C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring.

polyether: selected from the group consisting of - (O-CH ₂ -CH (R)) _n -OH and - (O-CH ₂ -CH (R)) _n -H where R is independently selected from: hydrogen, alkyl, aryl , halogen and n is from 1 to 250

silylalkyl: the group -SiR ₃ wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 and amine (to give sulphonamide) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; C1C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring

silylalkyloxy: the group -OSiR ₃ , wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; C1-C6-alkyl-C6H5 and amine (to give sulphonamide) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; C1C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring

Unless otherwise stated, the following groups are more preferred groups within the general group definition:

alkyl: linear and branched C1-C6-alkyl,

long-chain alkyls: linear and branched C5-C10 alkyl, preferably C6-C8 alkyl

alkenyl: C3-C6 alkenyl,

cycloalkyl: C6-C8-cycloalkyl,

alkoxy: C 1 -C 4 -alkoxy,

long-chain alkoxy: linear and branched C5-C10 alkoxy, preferably linear C6-C8 alkoxy

alkylene: selected from the group comprising: methylene; 1,2-ethylene; 1,3-propylene; butan-2-ol-1,4-diyl; 1,4-butylene; cyclohexane-1,1-diyl; cyclohexane-1,2-diyl; cyclohexane-1,4-diyl; cyclopentane-1,1-diyl; and cyclopentane-1,2-diyl,

aryl: selected from the group comprising: phenyl; biphenyl; naphthyl; anthracenyl; and phenanthrenyl,

arylenes: selected from the group comprising: 1,2-phenylenes; 1,3-phenylene; 1,4-phenylene; 1,2-naphtalenylene; 1,4-naphtalenylene; 2,3-naphthalenylenes and 1-hydroxy-2,6-phenylenes,

heteroaryl: selected from the group comprising: pyridinyl; pyrimidinyl; chinoninyl; pyrazolyl; triazolyl; isochinoninyl; imidazolyl; and oxazolidinyl, wherein the heteroaryl may be linked to the compound via any atom in the ring of the selected heteroaryl,

heteroarylenes: selected from the group comprising: pyridine, 2,3-diyl; pyridin-2,4-diyl; pyridin-2,6-diyl; pyridine-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; isoquinolin-1,3-diyl; isoquinolin-1,4-diyl; pyrazol-3,5-diyl; and imidazole-2,4-diyl,

heterocycloalkyl: selected from the group comprising: pyrrolidinyl; morpholinyl; piperidinyl; piperidinyl; 1,4-piperazinyl; tetrahydrofuranyl; 1,4,7-triazacyclononanyl; 1,4,8,11-tetraazacyclotetradecanyl; 1,4,7,10,13-pentaazacyclopentadecanyl; 1,4,7,10-tetraazacyclododecanyl; and piperazinyl, wherein the heteroaryl may be linked to the compound via any atom in the ring of the selected heteroaryl

heterocycloalkylenes: selected from the group comprising: piperidin-2,6-ylenes; piperidin-4,4-ylidene; 1,4-piperazin-1,4-ylene; 1,4-piperazin-2,3-ylene; 1,4-piperazin-2,6-ylene; tetrahydrothiophen-2,5-ylene; tetrahydrothiophen-3,4-ylene; tetrahydrofuran-2,5-ylene; tetrahydrofuran-3,4-ylene; pyrrolidin-2,5-ylene; pyrrolidin-2,2-ylidene; 1,4,7-triazacyclonon-1,4-ylene; 1,4,7-triazacyclonon-2,3-ylene; 1,4,7-triazacyclonon-2,2-ylidene; 1,4,8,11-tetraazacyclotetradec-1,4-ylene; 1,4,8,11-tetraazacyclotetradec-1,8-ylene; 1,4,8,11-tetraazacyclotetradec-2,3-ylene; 1,4,8,11-tetraazacyclotetradec-2,2-ylidene; 1,4,7,10-tetraazacyclododec-1,4-ylene; 1,4,7,10-tetraazacyclododec-1,7-ylene; 1,4,7,10-tetraazacyclododec-2,3-ylene; 1,4,7,10-tetraazacyclododec-2,2-ylidene; 1,4,7,10,13-pentaazacyclopentadec-1,4-ylene; 1,4,7,10,13-pentaazacyclopentadec-1,7-ylene; 1,4-diaza-7-thia-cyclonone-1,4-ylene; 1,4-diaza-7-thia-cyclonon-2,3-ylene; 1,4-diaza-7-thie in cyclonon-2,2-ylidenes; 1,4-diaza-7-oxa-cyclonon-1,4-ylene; 1,4-diaza-7-oxa-cyclonon-2,3-ylene; 1,4-diaza-7-oxa-cyclonone-2,2-ylidenes; 1,4-dioxan-2,6-ylene; 1,4-dioxan-2,2-ylidene; tetrahydropyran-2,6-ylene; tetrahydropyran-2,5-ylene; and tetrahydropyran-2,2-ylidenes, a C 1 -C 6 -alkyl-heterocycloalkyl wherein the heterocycloalkyl is selected from the group consisting of: piperidinyl; 1,4-piperazinyl; tetrahydrofuranyl; 1,4,7-triazacyclononanyl; 1,4,8,11-tetraazacyclotetradecanyl; 1,4,7,10,13-pentaazacyclopentadecanyl; 1,4,7,10-tetraazacyclododecanyl; and pyrrolidinyl, wherein the heterocycloalkyll can be linked to the compound via any atom in the ring of the selected heterocycloalkyl

amine: the group -N (R) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; and benzyl,

halogen: selected from the group comprising: F and Cl,

sulphonates: the group -S (O) 2OR, where R is selected from: hydrogen; C1-C6-alkyl; N / A; K; mg; and Ca,

sulphate: the group -OS (O) 2OR, where R is selected from: hydrogen; C1-C6-alkyl; N / A; K; mg; and Ca,

sulphone: the group -S (O) 2 R, wherein R is selected from: hydrogen; C1-C6-alkyl; benzyl and amines selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; and benzyl,

carboxylate: the group -C (O) OR, wherein R is selected from hydrogen; N / A; K; mg; Ca; C1-C6-alkyl; and benzyl,

carbonyl: the group: -C (O) R, wherein R is selected from: hydrogen; C1-C6-alkyl; benzyl and amines selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; and benzyl,

phosphonates: the group -P (O) (OR) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; benzyl; N / A; K; mg; and Ca,

phosphates: the group -OP (O) (OR) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; benzyl; N / A; K; mg; and Ca,

phosphines: the group -P (R) 2, wherein each R is independently selected from: hydrogen; C1-C6-alkyl; and benzyl,

phosphine oxide: the group -P (O) R2, wherein R is independently selected from: hydrogen; C1-C6-alkyl; benzyl and amines selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; C1-C6-alkyl; and benzyl.

polyether: selected from the group consisting of - (O-CH ₂ -CH (R)) _n -OH and - (O-CH ₂ -CH (R)) _n -H where R is independently selected from: hydrogen, methyl, halogen and n is from 5 to 50, preferably 10 to 25.

M, M _n (n is an integer): metals wherein two metals M are independently selected unless otherwise indicated.

wobei R³ und R⁴ wie oben definiert sind, R⁵ und R⁶ unabhängig voneinander Wasserstoff, Alkyl, langkettiges Alkyl, Alkoxy, langkettiges Alkoxy, Cycloalkyl, Halogenalkyl, Aryl, Halogenaryl, Heteroaryl, Heterocycloalkylene, Heterocycloalkyl, Halogenheteroaryl, Alkenyl, Halogenalkenyl, Alkinyl, Halogenalkinyl, Ketoaryl, Halogenketoaryl, Ketoheteroaryl, Ketoalkyl, Halogenketoalkyl, Silylalkyl, Silylalkyloxy sei könen, wobei bei geeigneten Resten eine oder mehrere nicht-benachbarte CH₂-Gruppen unabhängig voneinander durch -O-, -S-, -NH-, -NR°-, -SiR°R°°-, -CO-, -COO-, -OCO-, -OCO-O-, -SO₂-, -S-CO-, -CO-S-, -CY¹=CY² oder -C≡C- ersetzt sein können und zwar derart, dass O und/oder S Atome nicht direkt miteinander verbunden sind, ebenfalls optional mit Aryl- oder Heteroaryl bevorzugt enthaltend 1 bis 30 C Atome ersetzt sind (endständige CH₃-Gruppen werden wie CH₂-Gruppen im Sinne von CH₂-H verstanden.)

und die Bindung zwischen den Ringkohlenstoffen eine Einfach- oder Doppelbindung sein kann.According to a preferred embodiment, the catalyst comprises an N-heterocyclic carbene ligand of the following structure:

wherein R ³ and R ^{4 are} as defined above, R ⁵ and R ^{6 are} independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, halo heteroaryl, alkenyl, haloalkenyl, Alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals contain one or more non-adjacent CH ₂ groups independently of one another by -O-, -S-, -NH-, - NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH ₃ - Groups are understood as CH ₂ groups in the sense of CH ₂ -H.)

and the bond between the ring carbons may be a single or double bond.

wobei R³, R⁴ und R⁵ wie oben definiert sind. According to a preferred embodiment of the invention, the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:

wherein R ³ , R ⁴ and R ^{5 are} as defined above.

R¹ oder R² entweder ein substituierter oder unsubstituerter Kohlenstoff oder ein Stickstoff sein können (wobei aber R¹ und R² nicht beide Stickstoff sind)
wobei die Bindung zwischen R¹ und R² eine Einfach- oder Doppelbindung sein kann wobei R⁷, R⁸, R⁹ und R¹⁰ unabhängig voneinander Wasserstoff, Alkyl, langkettiges Alkyl, Alkoxy, langkettiges Alkoxy, Cycloalkyl, Halogenalkyl, Aryl, Halogenaryl, Heteroaryl, Heterocycloalkylene, Heterocycloalkyl, Halogenheteroaryl, Alkenyl, Halogenalkenyl, Alkinyl, Halogenalkinyl, Ketoaryl, Halogenketoaryl, Ketoheteroaryl, Ketoalkyl, Halogenketoalkyl, Silylalkyl, Silylalkyloxy sei könen, wobei bei geeigneten Resten eine oder mehrere nicht-benachbarte CH₂-Gruppen unabhängig voneinander durch -O-, -S-, -NH-, -NR°-, -SiR°R°°-, -CO-, -COO-, -OCO-, -OCO-O-, -SO₂-, -S-CO-, -CO-S-, -CY¹=CY² oder -C≡C- ersetzt sein können und zwar derart, dass O und/oder S Atome nicht direkt miteinander verbunden sind, ebenfalls optional mit Aryl- oder Heteroaryl bevorzugt enthaltend 1 bis 30 C Atome ersetzt sind (endständige CH₃-Gruppen werden wie CH₂-Gruppen im Sinne von CH₂-H verstanden.)According to a preferred embodiment of the invention, the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:

R ¹ or R ² may be either a substituted or unsubstituted carbon or a nitrogen (but where R ¹ and R ^{2 are} not both nitrogen)
wherein the bond between R ¹ and R ^{2 may be} a single or double bond wherein R ⁷ , R ⁸ , R ⁹ and R ^{10 are} independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, Heteroaryl, heterocycloalkylenes, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals contain one or more non-adjacent CH ₂ groups independently of one another by O-, -S-, -NH-, -NR °, -SiR ° R °°, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S- CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally containing preferably aryl or heteroaryl 1 to 30 C atoms are replaced (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H).

wobei R⁷ und R⁹ wie oben definiert sind und X₁ und X₂ unabhängig voneinander O, NH oder CH₂ sein können.According to a preferred embodiment of the invention, the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:

wherein R ⁷ and R ^{9 are} as defined above and X ₁ and X _{2 can} independently be O, NH or CH ₂ .

According to a preferred embodiment of the invention, the catalyst comprises at least one chiral N-heterocyclic carbene ligand.

Surprisingly, it has been found that in many cases asymmetric hydrogenation is possible in the presence of (at least) one chiral N-heterocyclic carbene ligand. This surprising finding is thus of independent inventive significance.

• a) Reduktion des Heteroaromaten mit einem Katalysator, umfassend mindestens ein Rutheniumatom sowie mindestens einen chiralen N-Heterocyclischen Carbenliganden, in Gegenwart eines Reduktionsmittels

Thus, the present invention thus also relates to a process for the asymmetric hydrogenation of heteroaromatics comprising the step

• a) reduction of the heteroaromatic with a catalyst comprising at least one ruthenium atom and at least one chiral N-heterocyclic carbene ligand, in the presence of a reducing agent

Particularly reactive heteroaromatics are:

1.) Aromatic compounds contain five-membered aromatic rings with at least one heteroatom

Aromatic compounds contain five-membered aromatics having at least one heteroatom i. In particular (but not limited to) compounds containing a furan, thiophene or pyrrole ring are particularly reactive compounds. It has been found that with benzene-ligated compounds, i. such as (but not limited to) benzofuran or indole specifically only the heteroaromatic ring is hydrogenated. This is surprising since hydrogenation processes for the targeted asymmetric hydrogenation of the "heteroaromatic part" of these compounds are extremely rare.

Thus, the present invention more particularly relates to a catalyst and a hydrogenation process for the asymmetric hydrogenation of aromatic compounds comprising a heterocyclic five-membered aromatic.

2.) Aromatic compounds contain six-membered aromatics with one heteroatom

Aromatic compounds comprising a six-membered aromatic having at least one heteroatom have also been found to be reactive compounds. Thus, the present invention more particularly relates to a catalyst and a hydrogenation process for the asymmetric hydrogenation of aromatic compounds comprising a six-membered aromatic having at least one heteroatom.

However, in practice, in some classes of applications, this class of compounds has been shown to hydrogenate, partially or even predominantly, the non-heterocyclic ring (benzene ring) in benzene-based compounds (such as quinoxalines) depending on the specific reaction conditions; this must be taken into account in practice.

If the heteroatom is both part of a five-membered ring and a six-membered ring (as in indolizine), it has been found that most of the six-membered ring is preferably hydrogenated.

R¹ oder R² entweder ein substituierter oder unsubstituerter Kohlenstoff oder ein Stickstoff sein können (wobei aber R¹ und R² nicht beide Stickstoff sind)
wobei die Bindung zwischen R¹ und R² eine Einfach- oder Doppelbindung sein kann
wobei R¹¹, R¹², R¹³ und R¹⁴ unabhängig voneinander Alkyl, langkettiges Alkyl, Alkoxy, langkettiges Alkoxy, Cycloalkyl, Halogenalkyl, Aryl, Halogenaryl, Heteroaryl, Heterocycloalkylene, Heterocycloalkyl, Halogenheteroaryl, Alkenyl, Halogenalkenyl, Alkinyl, Halogenalkinyl, Ketoaryl, Halogenketoaryl, Ketoheteroaryl, Ketoalkyl, Halogenketoalkyl, Silylalkyl, Silylalkyloxy sei könen, wobei bei geeigneten Resten eine oder mehrere nicht-benachbarte CH₂-Gruppen unabhängig voneinander durch -O-, -S-, -NH-, -NR°-, -SiR°R°°-, -CO-, -COO-, -OCO-, -OCO-O-, -SO₂-, -S-CO-, -CO-S-, -CY¹=CY² oder -C≡C- ersetzt sein können und zwar derart, dass O und/oder S Atome nicht direkt miteinander verbunden sind, ebenfalls optional mit Aryl- oder Heteroaryl bevorzugt enthaltend 1 bis 30 C Atome ersetzt sind (endständige CH₃-Gruppen werden wie CH₂-Gruppen im Sinne von CH₂-H verstanden.)According to a preferred embodiment of the invention, the catalyst comprises the abovementioned N-heterocyclic carbenes, except that these are optionally chiral. Particular preference is given to the following N-heterocyclic carbenes or their enantiomers (either as sole ligands or in combination):

R ¹ or R ² may be either a substituted or unsubstituted carbon or a nitrogen (but where R ¹ and R ^{2 are} not both nitrogen)
wherein the bond between R ¹ and R ^{2 may be} a single or double bond
where R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are each independently alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, Haloketoaryl, ketoheteroaryl, ketoalkyl, haloketalkyl, silylalkyl, silylalkyloxy may be konen, where suitable radicals one or more non-adjacent CH ₂ groups independently of each other by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C ≡C- can be replaced in such a way that O and / or S atoms are not directly connected to one another, likewise optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH ₃ groups are as CH ₂ - Understood groups in the sense of CH ₂ -H.)

Preferably R ¹¹ = R ¹³ and R ¹² = R ¹⁴ . This has proven particularly useful in practice.

Furthermore, when R ^{11 is} an aromatic or heteroaromatic (or structures derived therefrom), R ¹² is preferably nonaromatic, and it is also preferred that when R ^{13 is} an aromatic or heteroaromatic (or structures derived therefrom), R ^{14 is} not. is aromatic.

wobei R¹¹ und R¹³ wie oben definiert sind und X₁ und X₂ unabhängig voneinander O, NH oder CH₂ sein können. Bevorzugt ist R¹¹ = R¹³.Alternatively or additionally preferred are N-heterocyclic carbene ligands of the following structure (or, of course, their enantiomers):

wherein R ¹¹ and R ^{13 are} as defined above and X ₁ and X _{2 may} independently be O, NH or CH ₂ . Preferably, R ¹¹ = R ¹³ .

The process according to the invention is preferably carried out (be it for asymmetric or non-asymmetric hydrogenation) using hydrogen as the reducing agent. In this case, a hydrogen pressure of ≥6 bar is preferred.

According to an alternative embodiment of the invention isopropanol is used as the reducing agent (optionally using an increased excess of base).

According to a still alternative embodiment of the invention, the reducing agent used is form salts or formate.

The process (be it for asymmetric or non-asymmetric hydrogenation) is preferably carried out in an organic solvent; in practice, these have proven useful (and are therefore preferred): hexane, cyclohexane, toluene, xylene, mesitylene, dioxane, Diethyl ether, THF or mixtures of these solvents.

Preferably, the process is carried out at a temperature of ≥ 0 ° C. The upper limit is basically limited only by the boiling point of the solvent used. More preferred are temperatures of ≥ 10 ° C to ≤ 80 ° C, most preferably ≥ 15 ° C to ≤ 60 ° C.

If a step a0) (preparation of the catalyst) is arranged upstream, it is particularly preferred that this step is carried out at higher temperatures than in step a). In particular, (if the solvent allows these temperatures), temperatures of ≥ 60 ° C to ≤ 100 ° C, most preferably ≥ 70 ° C to ≤ 80 ° C, have proven useful.

As mentioned, according to a preferred embodiment of the invention, the catalyst can be prepared in situ from suitable precursors.

This can be done by using a sufficiently labile ruthenium complex (eg Ru (cod) (2-methylallyl) ₂ or other suitable complexes) and a salt derivative of the N-heterocyclic carbene in the presence of a strong base.

Suitable salts are e.g. Halides, triflates, tetrafluoroborates, tetraalkyl or arylborates, hexafluoroantimonates, hexafluorophosphates.

Alcoholates, in particular XOt-Bu (where X = Na, Li or K) or amides such as XHDMS (X = Li or K), LDA, are particularly suitable as base. Preferably, the base is used in a slight excess, with a 1.5 to 2facher excess has proven.

As already mentioned, one or more N-heterocyclic ligands may be present in the catalyst; this can be adjusted by the ratio of ruthenium precursor to N-heterocyclic salt precursor.

But it is also possible to prepare the catalyst in pure form and use; in practice, however, this is dispensed with because of the usually relative instability of the catalysts.

werden folgende Katalysatorstrukturen postuliert:The structure of the catalyst of some embodiments of the present invention was investigated by mass spectrometry and, for example, for the two following ligands

the following catalyst structures are postulated:

However, the present invention is expressly not limited to catalysts of this type.

Further details, features and advantages of the subject matter of the invention will become apparent from the subclaims and from the following description of the accompanying examples, in which - by way of example - several embodiments of the method according to the invention are shown. The examples are purely illustrative and not restrictive.

A) Hydrogenation of benzofurans 2a-o to the corresponding 2,3-dihydrobenzofurans 3a-o

General Test Procedure A (AVV A)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1 (14.1 mg, 0.03 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated to a pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon to a glass jar containing benzofuran 2a-o (0.3 mmol) and a stir bar. Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (10 bar) and vented before a reaction pressure of 10 bar was set. The reaction mixture was stirred at 25 ° C for 16 h. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 3a-o was obtained as analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). The enantiomeric ratio of all compounds was determined by HPLC on a chiral stationary phase. General Test Procedure B (AVV B)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1a (14.1 mg, 0.03 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated in a heated, pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon to a glass jar containing benzofuran 2a-o (0.3 mmol) and a stir bar. Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (60 bar) and vented before a reaction pressure of 60 bar was set. The reaction mixture was stirred at 40 ° C for each time indicated. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 3a-o was obtained as analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). The enantiomeric ratio of all compounds was determined by HPLC on a chiral stationary phase. 2-phenyl-2,3-dihydrobenzofuran (3a)

According to AVV A, 2-phenyl-2,3-dihydrobenzofuran (3a) was obtained as a colorless oil after a reaction time of 16 h (58.8 mg, 0.3 mmol, quantitative, 99: 1).
[α] ²⁴ _D = -40.0 (c 1.00, CH ₂ Cl ₂ ), RF (pentane): 0.81; ¹ H NMR (300 MHz, CDCl _3): 7:29 to 7:17 (m, 5H), 7:05 (m, 2H), 6.75 (m, 2H), 5.62 (dd, J = 9.2, 8.5 Hz, 1H), 3:49 ( dd, J = 15.6, 9.5 Hz, 1H), 3.08 (dd, J = 15.6, 8.2 Hz, 1H); ¹³ C NMR (75 MHz, CDCl _3): 159.8, 142.1, 128.8, 128.3, 128.1, 126.6, 125.9, 124.9, 120.8, 109.5, 84.1, 38.5; GC-MS: R _t (50_40): 8.6 min; EI: 51 (14), 63 (13), 77 (13), 82 (10), 89 (19), 115 (10), 118 (10), 152 (18), 165 (35), 167 (22 ), 177 (12), 178 (12), 179 (15), 181 (15), 194 (24), 195 (60), 196 (100), 197 (16); ATR-FTIR (cm ^-1 ): 3033, 2915, 1596, 1478, 1461, 1365, 1327, 1308, 1229, 1172, 1099, 1077, 1015, 973, 930, 861, 746, 696, 601, 534; HPLC (AD-H, elute: hexane / i-PrOH = 97/3, detector: 230 nm, flow rate: 1 mL / min), t _{1 (main)} = 5.0 min, t _{2 (lower)} = 5.5 min. 2- (o-tolyl) -2,3-dihydrobenzofuran (3b)

According to AAV B, 2- (o-tolyl) -2,3-dihydrobenzofuran (3b) was obtained after a reaction time of 48 h and purification by column chromatography on silica gel (pentane) as a colorless oil (46.2 mg, 0.22 mmol, 73%; 4 he). 2- (m-tolyl) -2,3-dihydrobenzofuran (3c)

According to AAV B, 2- (m-tolyl) -2,3-dihydrobenzofuran (3c) was obtained as a colorless oil after a reaction time of 16 h (63.1 mg, 0.3 mmol, quantitative, 99: 1). 2- (p-tolyl) -2,3-dihydrobenzofuran (3d)

According to AAV B, 2- (p-tolyl) -2,3-dihydrobenzofuran (3d) was obtained as a colorless oil after a reaction time of 16 h (63.1 mg, 0.3 mmol, quantitative, 99: 1). 2- (4-methoxyphenyl) -2,3-dihydrobenzofuran (3e)

According to AAV B, 2- (4-methoxyphenyl) -2,3-dihydrobenzofuran (3e) was obtained as a colorless oil after a reaction time of 16 h (67.9 mg, 0.3 mmol, quantitative, 99: 1). 2- (4- (Trifluoromethyl) phenyl) -2,3-dihydrobenzofuran (3f)

According to AAV B, 2- (4- (trifluoromethyl) phenyl) -2,3-dihydrobenzofuran (3f) was obtained as a colorless solid after a reaction time of 16 h (79.3 mg, 0.3 mmol, quantitative, 98.5: 1.5 er). 2- (4-fluorophenyl) -2,3-dihydrobenzofuran (3g)

According to AAV A, 2- (4-fluorophenyl) -2,3-dihydrobenzofuran (3g) was obtained as a colorless solid after a reaction time of 16 h (64.2 mg, 0.3 mmol, quantitative, 99: 1). (R) -2-methyl-2,3-dihydrobenzofuran (3h)

According to AAV A, (R) -2-methyl-2,3-dihydrobenzofuran (3h) was obtained as a colorless oil after a reaction time of 16 h (40.3 mg, 0.3 mmol, quantitative, 96: 4 er). Stereochemistry was assigned by comparison with literature data. 2-butyl-2,3-dihydrobenzofuran (3i)

According to AAV A, 2-butyl-2,3-dihydrobenzofuran (3i) was obtained as a colorless oil after a reaction time of 16 h (52.8 mg, 0.3 mmol, quantitative, 95: 5 er). 2-decyl-2,3-dihydrobenzofuran (3j)

According to AAV A, 2-decyl-2,3-dihydrobenzofuran (3j) was obtained as a colorless solid after a reaction time of 16 h (78.1 mg, 0.3 mmol, quantitative, 94: 6 er). 2-Isopropyl-2,3-dihydrobenzofuran (3k)

According to AAV A, 2-isopropyl-2,3-dihydrobenzofuran (3k) was obtained as a colorless oil after a reaction time of 16 h (48.7 mg, 0.3 mmol, quantitative, 93.5: 6.5 er). 2- (tert-butyl) -2,3-dihydrobenzofuran (3l)

According to AAV B, 2- (tert-butyl) -2,3-dihydrobenzofuran (3l) was obtained as a colorless oil after a reaction time of 16 h and purification by column chromatography on silica gel (pentane) (20.1 mg, 0.11 mmol, 38%, 87.5: 12.5 he). 2-Benzyl-2,3-dihydrobenzofuran (3m)

According to AAV A, 2-benzyl-2,3-dihydrobenzofuran (3m) was obtained as a colorless oil after a reaction time of 16 h (63.1 mg, 0.3 mmol, quantitative, 92: 8 er). 6- (tert -butyl) -2-phenyl-2,3-dihydrobenzofuran (3n)

According to AAV A, 6- (tert-butyl) -2-phenyl-2,3-dihydrobenzofuran (3n) was obtained as a colorless oil after a reaction time of 16 h (75.7 mg, 0.3 mmol, quantitative, 99: 1). 3-methyl-2,3-dihydrobenzofuran (3o)

2-Phenyl-2,3-dihydrobenzofuran (3a)

According to AAV A, 3-methyl-2,3-dihydrobenzofuran (3o) was obtained as a colorless oil after a reaction time of 16 h (40.3 mg, 0.3 mmol, quantitative, 93: 7 er). Modified AVV A: Use of ligand 1c instead of ligand 1a

2-phenyl-2,3-dihydrobenzofuran (3a)

According to modified AVV A (using ligand 1c instead of 1a), 2-phenyl-2,3-dihydrobenzofuran (3a) was obtained as a colorless oil after a reaction time of 16 h (58.8 mg, 0.3 mmol, quantitative, 94: 6 e.r.).

B) Hydrogenation of benzothiophenes 4a-c to the corresponding 2,3-dihydrobenzo-thiophenes 5a-c

General Test Procedure C (AVV C)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1a (14.1 mg, 0.03 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated in a heated, pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon to a glass jar containing benzothiophene 4a-c (0.3 mmol) and a stir bar. Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (65 bar) and vented before a reaction pressure of 65 bar was set. The reaction mixture was stirred at 25 ° C for the given time. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 5a-c was obtained as analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). The enantiomeric ratio of all compounds was determined by HPLC on a chiral stationary phase. 2-methyl-2,3-dihydrobenzothiophene (5a)

According to AAV C, 2-methyl-2,3-dihydrobenzothiophene (5a) was obtained as a colorless oil after a reaction time of 16 h (45.1 mg, 0.3 mmol, quantitative, 99: 1). 2-butyl-2,3-dihydrobenzothiophene (5b)

According to AAV C, 2-butyl-2,3-dihydrobenzothiophene (5b) was obtained after a reaction time of 48 h and purification by column chromatography on silica gel (pentane) as a colorless oil (49.0 mg, 0.26 mmol, 85%, 99: 1). 2-Benzyl-2,3-dihydrobenzothiophene (5c)

According to AAV C, 2-benzyl-2,3-dihydrobenzothiophene (5c) was obtained after a reaction time of 48 h in a ratio of product 5c (75%) to starting material 4c (25%) based on ¹ H-NMR. A column chromatographic purification was not performed (5c = 98: 2 er). Modified AVV C: Use of ligand 1d instead of ligand 1a, 30 bar H ₂ (instead of 65 bar), 40 ° C reaction temperature (instead of 25 ° C).

2-methyl-2,3-dihydrobenzothiophene (5a)

According to modified AAV C, 2-methyl-2,3-dihydrobenzothiophene (5a) was reacted after a reaction time of 16 h at 30 bar and 40 ° C in a ratio of product 5a (50%) to starting material 4a (50%) based on GC Received MS. Column chromatographic purification was not performed (5a = 68:32 e.r.).

C) Hydrogenation of furan 6a and thiophene 8a to the corresponding tetrahydrofuran 7a and tetrahydrothiophene 9a

General Test Procedure D (AVV D)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1a (14.1 mg, 0.03 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated in a heated, pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon into a glass jar containing furan 6a or thiophene 8a (0.3 mmol) and a stir bar. Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was sealed and filled three times each with hydrogen gas (10 bar for 6a and 65 bar for 8a, respectively) and vented before adjusting a reaction pressure of 10 bar (6a) and 65 bar (8a), respectively. The reaction mixture was stirred at 25 ° C for 16 h. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. The reaction mixture was analyzed by ¹ H NMR and GC MS, respectively. The enantiomeric ratio of the compound was determined by HPLC on a chiral stationary phase. 2-phenyltetrahydrofuran (7a)

According to AAV D, 2-phenylfuran (6a) was completely converted to 2-phenyltetrahydrofuran (7a) after a reaction time of 16 h at a hydrogen pressure of 10 bar (GC MS was used) (7a = 60:40 er). 2-ethyl-5-phenyltetrahydrothiophene (9a)

According to AAV D, 2-ethyl-5-phenyltetrahydrothiophene (9a) was obtained after a reaction time of 16 h and a hydrogen pressure of 65 bar as a mixture of 9a (28%) to starting material 8a (72%) based on ¹ H NMR of the reaction mixture (9a = 95: 5 he).

D) Hydrogenation of indolizines 10a-b to the corresponding 5,6,7,8-tetrahydroindolizines 11a-b

General Test Procedure E (AVV E)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1a (14.1 mg, 0.03 mmol) and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated in a heated, pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon into a glass vessel containing indolizine 10a-b (0.3 mmol) and a stirring fish (work under exclusion of light!). Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (10 bar) and vented before a reaction pressure of 10 bar was set. The reaction mixture was stirred at 25 ° C for 16 h. After the reactor was vented gently, the reaction mixture was poured through a frit filtered with silica gel, using pentane: EtOAc (9: 1) and then freed from the solvent under reduced pressure. The reaction mixture was analyzed by ¹ H NMR and GC MS. The enantiomeric ratio of compound 11a-b was determined by HPLC on a chiral stationary phase. 3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (11a)

According to AAV E, 3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (11a) was obtained after a reaction time of 16 h and a hydrogen pressure of 10 bar as a mixture of 11a (90%) to starting material 10a (10 %) based on ¹ H NMR of the reaction mixture (11a = 97: 3 er). 5-methyl-2-phenyl-5,6,7,8-tetrahydroindolizine (11b)

According to AAV E, 5-methyl-2-phenyl-5,6,7,8-tetrahydroindolizine (11b) was obtained after a reaction time of 16 h and a hydrogen pressure of 10 bar as a mixture of 11b (50%) to starting material 10b (50 %) based on ¹ H NMR of the reaction mixture (11b = 93: 7). Modified AVV E: Use of ligand 1c instead of ligand 1a, 65 bar H ₂ (instead of 10 bar), 60 ° C reaction temperature (instead of 25 ° C).

3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (11a)

According to modified AAV E, 3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (11a) was obtained after a reaction time of 16 h and a hydrogen pressure of 65 bar at 60 ° C. as a mixture of 11a (83%). to starting material 10a (17%) based on ¹ H NMR of the reaction mixture (11a = 85:15).

E) Hydrogenation of benzofurans 12a-o to the corresponding 2,3-dihydrobenzofurans 13a-o

General Test Procedure F (AVV F)

In a glovebox were added [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1b (8.0 mg, 0.03 mmol), dry KOt-Bu (5.0 mg, 0.045 mmol) and benzofuran 12a. Weighed 0 (0.15 mmol) into a glass vessel with stirring magnet. Outside the glove box, the mixture was suspended under argon in hexane (2 mL) and then the glass jar placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (65 bar) and vented before a reaction pressure of 65 bar was set. The reaction mixture was stirred at 40 ° C for 16 h. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 13a-o was obtained as an analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). 2-phenyl-2,3-dihydrobenzofuran (13a)

According to AVV F, 2-phenyl-2,3-dihydrobenzofuran (13a) was obtained as a colorless oil after a reaction time of 16 h (29.4 mg, 0.15 mmol, quantitative, racemic).
R _F (pentane): 0.81; ¹ H NMR (300 MHz, CDCl _3): 7:29 to 7:17 (m, 5H), 7:05 (m, 2H), 6.75 (m, 2H), 5.62 (dd, J = 9.2, 8.5 Hz, 1H), 3:49 ( dd, J = 15.6, 9.5 Hz, 1H), 3.08 (dd, J = 15.6, 8.2 Hz, 1H); ¹³ C NMR (75 MHz, CDCl _3): 159.8, 142.1, 128.8, 128.3, 128.1, 126.6, 125.9, 124.9, 120.8, 109.5, 84.1, 38.5; GC-MS: R _t (50_40): 8.6 min; EI: 51 (14), 63 (13), 77 (13), 82 (10), 89 (19), 115 (10), 118 (10), 152 (18), 165 (35), 167 (22 ), 177 (12), 178 (12), 179 (15), 181 (15), 194 (24), 195 (60), 196 (100), 197 (16); ATR-FTIR (cm ^-1 ): 3033, 2915, 1596, 1478, 1461, 1365, 1327, 1308, 1229, 1172, 1099, 1077, 1015, 973, 930, 861, 746, 696, 601, 534. 2 - (o-tolyl) -2,3-dihydrobenzofuran (13b)

According to AAV F, 2- (o-tolyl) -2,3-dihydrobenzofuran (13b) was obtained as a colorless oil after a reaction time of 48 h and purification by column chromatography on silica gel (pentane) (28.4 mg, 0.13 mmol, 90%, racemic). , 2- (m-tolyl) -2,3-dihydrobenzofuran (13c)

According to AAV F, 2- (m-tolyl) -2,3-dihydrobenzofuran (13c) was obtained as a colorless oil after a reaction time of 16 h (31.5 mg, 0.15 mmol, quantitative, racemic). 2- (p-tolyl) -2,3-dihydrobenzofuran (13d)

According to AAV F, 2- (p-tolyl) -2,3-dihydrobenzofuran (13d) was obtained as a colorless oil after a reaction time of 16 h (31.5 mg, 0.15 mmol, quantitative, racemic). 2- (4-methoxyphenyl) -2,3-dihydrobenzofuran (13e)

According to AAV F, 2- (4-methoxyphenyl) -2,3-dihydrobenzofuran (13e) was obtained as a colorless oil after a reaction time of 16 h (33.9 mg, 0.15 mmol, quantitative, racemic). 2- (4- (Trifluoromethyl) phenyl) -2,3-dihydrobenzofuran (13f)

According to AAV F, 2- (4- (trifluoromethyl) phenyl) -2,3-dihydrobenzofuran (13f) was obtained as a colorless solid after a reaction time of 16 h (39.6 mg, 0.15 mmol, quantitative, racemic). 2- (4-fluorophenyl) -2,3-dihydrobenzofuran (13g)

According to AAV F, 2- (4-fluorophenyl) -2,3-dihydrobenzofuran (13g) was obtained as a colorless solid after a reaction time of 16 h (32.1 mg, 0.15 mmol, quantitative, racemic). 2-methyl-2,3-dihydrobenzofuran (13h)

According to AAV F, 2-methyl-2,3-dihydrobenzofuran (13h) was obtained as a colorless oil after a reaction time of 16 h (20.1 mg, 0.15 mmol, quantitative, racemic). 2-butyl-2,3-dihydrobenzofuran (13i)

According to AAV F, 2-butyl-2,3-dihydrobenzofuran (13i) was obtained as a colorless oil after a reaction time of 16 h (26.4 mg, 0.15 mmol, quantitative, racemic). 2-decyl-2,3-dihydrobenzofuran (13j)

According to AAV F, 2-decyl-2,3-dihydrobenzofuran (13j) was obtained as a colorless solid after a reaction time of 16 h (39.1 mg, 0.15 mmol, quantitative, racemic). 2-Isopropyl-2,3-dihydrobenzofuran (13k)

According to AAV F, 2-isopropyl-2,3-dihydrobenzofuran (13k) was obtained as a colorless oil after a reaction time of 16 h (24.3 mg, 0.15 mmol, quantitative, racemic). 2- (tert-butyl) -2,3-dihydrobenzofuran (13l)

According to AAV F, 2- (tert-butyl) -2,3-dihydrobenzofuran (13l) was obtained as a colorless oil after a reaction time of 16 h and purification by column chromatography on silica gel (pentane) (13.2 mg, 0.075 mmol, 50%, racemic). , 2-Benzyl-2,3-dihydrobenzofuran (13m)

According to AAV F, 2-benzyl-2,3-dihydrobenzofuran (13m) was obtained as a colorless oil after a reaction time of 16 h (31.5 mg, 0.15 mmol, quantitative, racemic). 6- (tert -butyl) -2-phenyl-2,3-dihydrobenzofuran (13n)

According to AAV F, 6- (tert-butyl) -2-phenyl-2,3-dihydrobenzofuran (13n) was obtained as a colorless oil after a reaction time of 16 h (37.8 mg, 0.15 mmol, quantitative, racemic). 3-methyl-2,3-dihydrobenzofuran (13o)

According to AAV F, 3-methyl-2,3-dihydrobenzofuran (13o) was obtained as a colorless oil after a reaction time of 16 h (20.1 mg, 0.15 mmol, quantitative, racemic).

F) Hydrogenation of benzothiophenes 14a-c to the corresponding 2,3-dihydrobenzo-thiophenes 15a-c

General Test Specification G (AVV G)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1b (8.0 mg, 0.03 mmol), and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated to a pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon to a glass jar containing benzothiophene 14a-c (0.15 mmol) and a stir bar. Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (65 bar) and vented before a reaction pressure of 65 bar was set. The reaction mixture was stirred at 40 ° C for the given time. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 15a-c was obtained as analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). 2-methyl-2,3-dihydrobenzothiophene (15a)

According to AAV G, 2-methyl-2,3-dihydrobenzothiophene (15a) was obtained as a colorless oil after a reaction time of 16 h (22.5 mg, 0.15 mmol, quantitative, racemic). 2-butyl-2,3-dihydrobenzothiophene (15b)

According to AAV G, 2-butyl-2,3-dihydrobenzothiophene (15b) was obtained as a colorless oil after a reaction time of 16 h and purification by column chromatography on silica gel (pentane) (12.0 mg, 0.06 mmol, 40%, racemic). 2-Benzyl-2,3-dihydrobenzothiophene (15c)

According to AAV G, 2-benzyl-2,3-dihydrobenzothiophene (15c) was obtained after a reaction time of 16 h in a ratio of product 15c (48%) to starting material 14c (52%) based on ¹ H-NMR. A column chromatographic purification was not performed.

G) Hydrogenation of furan 16a and thiophene 18a to the corresponding tetrahydrofuran 17a and tetrahydrothiophene 19a

General Test Procedure H (AVV H)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1b (8.0 mg, 0.03 mmol), dry KOt-Bu (5.0 mg, 0.045 mmol), and furan 16a ( 0.15 mmol) or thiophene 18a (0.15 mmol) was weighed into a glass vessel with stirring magnet. Outside the glove box, the mixture was suspended under argon in hexane (2 mL) and then the glass jar placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (65 bar) and vented before a reaction pressure of 65 bar was set. The reaction mixture was stirred at 40 ° C for 16 h. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. Compound 17a or 19a was obtained as analytically pure substance. In the case of an incomplete reaction, the product was separated from the starting material by column chromatography on silica gel (pentane) (see individual compound). 2-phenyltetrahydrofuran (17a)

According to AAV H, 2-phenylfuran (16a) was completely converted to 2-phenyltetrahydrofuran (17a) after a reaction time of 16 h at a hydrogen pressure of 65 bar (22.2 mg, 0.15 mmol, quantitative, racemic). 2-ethyl-5-phenyltetrahydrothiophene (19a)

According to AAV H, 2-ethyl-5-phenyltetrahydrothiophene (19a) was obtained after a reaction time of 16 h and a hydrogen pressure of 65 bar as a mixture of 19a (44%) to starting material 18a (56%) based on GC MS of the reaction mixture.

H) Hydrogenation of indolizines 20a-b to the corresponding 5,6,7,8-tetrahydroindolizines 21a-b

General Test Procedure I (AVV I)

In a glovebox, [Ru (cod) (2-methylallyl) ₂ ] (4.8 mg, 0.015 mmol), imidazolium salt 1b (8.0 mg, 0.03 mmol), and dry KOt-Bu (5.0 mg, 0.045 mmol) were heated to a pressure stable reaction vessel weighed with stirring magnet. Outside the glovebox, the mixture was suspended under argon in hexane (2 mL) and stirred at 70 ° C for 12 h. The suspension was transferred under argon into a glass vessel containing indolizine 20a-b (0.15 mmol) and a stirring fish (work under exclusion of light!). Subsequently, the glass jar was placed in a 150 mL stainless steel high pressure reactor under argon. The reactor was closed and filled three times with hydrogen gas (65 bar) and vented before a reaction pressure of 65 bar was set. The reaction mixture was stirred at 60 ° C for 16 h. After venting the reactor gently, the reaction mixture was filtered through a frit filled with silica gel using pentane: EtOAc (9: 1) and then freed of solvent under reduced pressure. 3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (21a)

According to AAV I, 3-butyl-5-methyl-5,6,7,8-tetrahydroindolizine (21a) was obtained as a greenish oil after a reaction time of 16 h and a hydrogen pressure of 65 bar (28.7 mg, 0.15 mmol, quantitative, racemic ). 5-methyl-2-phenyl-5,6,7,8-tetrahydroindolizine (21b)

According to AAV I, 5-methyl-2-phenyl-5,6,7,8-tetrahydroindolizine (21b) was added after a reaction time of 16 h and a hydrogen pressure of 65 bar as a mixture of 21b (40%) to starting material 20b (60 %) based on ¹ H NMR of the reaction mixture.

The individual combinations of the components and the features of the already mentioned embodiments are exemplary; the exchange and substitution of these teachings with other teachings contained in this document with the references cited are also expressly contemplated. Those skilled in the art will recognize that variations, modifications and other implementations described herein may also occur without departing from the spirit and scope of the invention. Accordingly, the above description is illustrative and not restrictive. The word used in the claims does not exclude other ingredients or steps. The indefinite article "a" does not exclude the meaning of a plural. The mere fact that certain measures are recited in mutually different claims does not make it clear that a combination of these dimensions can not be used to advantage. The scope of the invention is defined in the following claims and the associated equivalents.

Claims (10)

Catalyst for the hydrogenation of heteroaromatics provided comprising at least one ruthenium atom and at least one N-heterocyclic carbene ligand Catalyst according to claim 1 comprising at least one N-heterocyclic carbene ligand of the following structure

wherein R ¹ or R ² may be either a substituted or unsubstituted carbon or a substituted or unsubstituted carbon nitrogen (but where R ¹ and R ^{2 are} not both nitrogen), the substitutions being selected from (independently of one another) alkyl, long-chain alkyl, Alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, Haloketoaryl, ketoheteroaryl, ketoalkyl, haloketalkyl, silylalkyl, silylalkyloxy may be konen, where suitable radicals one or more non-adjacent CH ₂ groups independently of each other by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C ≡C- can be replaced in such a way that O and / or S atoms are not directly connected to one another, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH ₃ groups are as CH ₂ - groups within the meaning of CH ₂ -H understood.) R ³ and R ⁴ are independently alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylenes, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, Haloalkynyl, ketoaryl, haloketoaryl, Ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy may be könen, where suitable R one or more non-adjacent CH ₂ groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO- , -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 carbon atoms are replaced (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H). The bond between R ¹ and R ^{2 may be} a single or double bond and R ¹ and R ³ on the one hand and / or R ² and R ⁴ on the other hand may be substituted so that between R ¹ and R ³ or R ² and R ^{4 forms} a ring. Catalyst according to claim 1 or 2, comprising an N-heterocyclic carbene ligand of the following structures

wherein R ³ and R ^{4 are} as defined above, R ⁵ and R ^{6 are} independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, halo heteroaryl, alkenyl, haloalkenyl, Alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals contain one or more non-adjacent CH ₂ groups independently of one another by -O-, -S-, -NH-, - NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH ₃ - Groups are understood as CH ₂ groups in the sense of CH ₂ -H.)

wherein R ³ , R ⁴ and R ^{5 are} as defined above;

wherein R ¹ and R ^{2 are} as defined above, R ⁷ , R ⁸ , R ⁹ and R ^{10 are} independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, Halogenoheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals contain one or more non-adjacent CH ₂ groups independently of one another by -O-, -S- , -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO-, -CO- S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms replaced (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H) as well as

wherein R ⁷ and R ^{9 are} as defined above and X ₁ and X _{2 can} independently be O, NH or CH ₂ . Catalyst according to one of claims 1 to 3, comprising at least one chiral N-heterocyclic carbene ligand Catalyst according to one of claims 1 to 4, comprising at least one N-heterocyclic carbene ligand of the following structures and / or their enantiomers:

wherein R ¹ or R ² may be either a substituted or unsubstituted carbon or a nitrogen (but where R ¹ and R ^{2 are} not both nitrogen) wherein the bond between R ¹ and R ^{2 may be} a single or double bond wherein R ¹¹ , R ¹² , R ¹³ and R ^{14 are} independently alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, Heterocycloalkylenes, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals contain one or more non-adjacent CH ₂ groups independently of one another by -O- , -S-, -NH-, -NR ° -, -SiR ° R °°, -CO-, -COO-, -OCO-, -OCO-O-, -SO ₂ -, -S-CO- , -CO-S-, -CY ¹ = CY ² or -C≡C- can be replaced in such a way that O and / or S atoms are not directly connected to each other, also optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H).

wherein R ¹¹ and R ^{13 are} as defined above and X ¹ and X ^{2 may} independently be O, NH or CH ₂ . Catalyst according to claim 5 wherein R ¹¹ = R ¹³ and (where present) R ¹² = R ¹⁴ . A process for the hydrogenation of heteroaromatics provided comprising the step a) reduction of the heteroaromatic with a catalyst according to any one of claims 1 to 7 in the presence of a reducing agent Method according to claim 7, comprising the step a0), carried out before step a) a0) in situ synthesis of the catalyst from suitable precursors A process according to claim 7 or 8, wherein the process is carried out with hydrogen as the reducing agent Method according to one of claims 7 to 9, wherein the method is carried out at a temperature of ≥ 0 ° C.