DE102018104201A1 - Process for the preparation of fluorinated heterocyclic aliphatic compounds - Google Patents

Abstract

The present invention relates to a novel process for preparing fluorinated heterocyclic aliphatic compounds from the analogous aromatic compounds by hydrogenation with a Rh catalyst system.

Description

The present invention relates to the field of fluorinated heterocyclic aliphatic compounds. Such compounds play a major role in the pharmaceutical or agrochemical field due to the polarity of the C-F bond with concomitant steric similarity to C-H bonds and other effects. Furthermore, additive dipole effects in several identically aligned C-F bonds are of interest for materials chemistry applications.

Despite the importance of these compounds, effective methods of preparation are not always available, so there is a continuing need for synthetic methods of fluorinated heterocyclic aliphatic cyclo compounds. This is especially true for heterocyclic compounds, as these are often important pharmaceuticals.

It is thus an object to provide novel methods for producing such compounds. This object is achieved by a method according to claim 1. Accordingly, there is provided a process for producing fluorinated heterocyclic aliphatic compounds comprising the step of hydrogenating a heteroaromatic fluorochemical precursor with a catalyst comprising at least one rhodium atom in the presence of a reducing agent.

Surprisingly, it has been found that in this way, often in excellent yield, the corresponding fluorine-containing heterocyclic aliphatic cyclo compounds are available and a FH exchange, as would have been expected in many analogous hydrogenations, either not at all or only to the extent that, nevertheless the fluorine-containing product can be obtained in an acceptable yield.

Surprisingly, in many applications a whole series of functional groups is tolerated such as e.g. Thioether groups, pinacol borane groups or protected hydroxy groups.

Furthermore, it has surprisingly been found that in the case where the starting substance contains two or more fluorine atoms, the cis product is preferably produced in many applications, which allows access to sterically defined products.

The term "aromatic fluorine-containing substance" is understood in particular to mean fluorinated heterocyclic 5 or 6 rings with π-electron septet as well as fluorinated annelated heteroaromatic multi-cycles.

It should be noted that the term "aromatic fluorine-containing substance" is understood in particular to mean that at least one fluorine is present as a substituent on an aromatic ring.

Alternatively preferred are aromatic fluorine-containing precursors containing one or more benzo-fused heteroaromatic rings.

The term "hydrogenation" is understood in particular to mean that in the sum of two hydrogens are added to a "double bond" of the aromatic compound. 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).

According to a preferred embodiment of the present invention, the catalyst comprises rhodium with at least one labile ligand, preferably more than one labile ligand.
These are understood to mean ligands whose bonding to the rhodium is so weak that, if appropriate, they are at least temporarily not bound to the rhodium in the course of the reaction.

Preferred labile ligands are alkenes, cyclic bisalkenes, halides, triflates, acetonitrile, weakly coordinating anions such as tetrafluoroborate or phosphines. Particularly preferred are alkenes, especially cyclic dialketen such as cyclooctadiene or bicyclo [2.2.1] hepta-2,5-diene.

Preferred catalysts according to a preferred embodiment of the invention are cyclooctadiene rhodium chloride dimer ([Rh (COD) Cl] ₂ ), bis (1,5-cyclooctadiene) rhodium (1) tetrafluoroborate, bis (acetonitrile) (1,5-cyclooctadiene) rhodium (I) tetrafluoroborate ([Rh (COD) (MeCN) 2] BF4), chlorobis (cyclooctene) rhodium (I), dimer [Rh (COE) 2Cl] 2, bicyclo [2.2.1] hepta-2,5-diene rhodium ( I) chloride, dimer ([Rh (NBD) Cl] ₂ , rhodium-phosphine Complex analogous to tris (triphenylphosphine) rhodium (I) chloride ([Rh (PPh ₃ ) ₃ Cl]) or tris (tricyclohexylphosphine) rhodium (I) chloride ([Rh (PCy ₃ ) ₃ Cl]), or bis (ethylene) rhodium chloride dimer ([Rh (C ₂ H ₄ ) ₂ Cl] ₂ .

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

According to an alternative preferred embodiment of the present invention, the catalyst does not comprise an N-heterocyclic carbene ligand.

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, Pyrrolidinylidenes, pyrrolidens, imidazolylidenes, imidazolidinylidenes, piperidinylenes, hexahydropyrimidinylenes and triazolylidenes. Particularly preferred are pyrrolidinylidenes, pyrrolidens, imidazolylidenes and imidazolidinylidenes, more preferably pyrrolidinylidenes.

In the event that the N-heterocyclic carbene ligand comprises a pyrrolidinylidene compound, it is especially preferred that there is no hydrogen in the α-position to both the nitrogen and the carbene. This has turned out to be particularly effective for the hydrogenation in most applications of the present invention, since so the activity of the catalyst is not lowered by enamine formation, etc.

1. a) in situ Synthese des in Schritt b) eingesetzten Katalysators aus geeigneten Vorstufen
2. b) Durchführen der Hydrierung wie oben und im weiteren beschrieben

According to a preferred embodiment, the catalyst is used in substance. However, according to alternative embodiments, it may also be advantageous to prepare the catalyst in situ. Thus, according to a preferred embodiment of the invention, the method according to the invention comprises two steps:

1. a) in situ synthesis of the catalyst used in step b) from suitable precursors
2. b) carrying out the hydrogenation as described above and in the following

Suitable rhodium-containing precursor is, in particular, the cyclooctadiene rhodium chloride dimer ([Rh (COD) Cl] ₂ ).

Preferably, step a) is carried out by reacting a suitable salt of the N-heterocyclic carbene with a strong base, preferably selected from NaOtBu, LDA, KOtBu, NaH, KHMDS, LiHMDS with a rhodium-forming precursor, for example [Rh (COD) Cl] 2 , If necessary, reacted at elevated temperature. Here, halides, pseudohalides such as oxygen-containing anions, in particular triflates and weakly coordinating anions such as tetrafluoroborate, hexafluoroantimonate or hexafluorophosphate can serve as anions. Preferred solvents here are hexane, diethyl ether or tetrahydrofuran.

If, in step b), a different solvent is used than in step a), the solvent is then optionally removed between the two steps.

wobei

• R¹ bis R⁵ 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.)
• R⁶ und R⁷ 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 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.)
• und R¹ bis R⁷ so substituiert sein können, dass sich wahlweise zwischen R² und R³, R⁴ und R³, R⁶ und R⁷, R¹ und R⁴/R⁵, R⁴/R⁵ und R⁶/R⁷oder R²/R³ und R⁶/R⁷ 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; benzothiophenyl, furyl, benzofuryl, 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 Cl-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; Cl- 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; Cl- 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; Cl-C6-alkyl-C6H5 und amine (to give amide) ausgewählt aus der Gruppe: -NR'2, wobei jedes R' unabhängig ausgewählt ist aus: Wasserstoff; Cl- 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; ClC6-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; ClC6-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

According 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 to R ⁵ independently of one another are alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl Silylalkyl, silylalkyloxy, where suitable radicals include one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO -, -COO-, -OCO-, -OCO-O-, -SO2-, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C = C- can be replaced in such a way in 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 (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H .)
• R ⁶ and R ⁷ are each independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl , Halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals include 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- may 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 groups in the sense of CH ₂ -H understood.)
• and R ¹ to R ^{7 may} be substituted to optionally between R ² and R ³ , R ⁴ and R ³ , R ⁶ and R ⁷ , R ¹ and R ⁴ / R ⁵ , R ⁴ / R ⁵ and R ⁶ / R ⁷ or R ² / R ³ and R ⁶ / R ^{7 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-phenylenes; 1,4-phenylene; 1,2-naphtalenylene; 1,3-naphtalenylene; 1,4-naphthalenylenes; 2,3-naphtalenylene; 1-hydroxy-2,3-phenylene; 1-hydroxy-2,4-phenylenes; 1-hydroxy-2,5-phenylenes; 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; benzothiophenyl, furyl, benzofuryl, 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; pyridine-3,4-diyl; pyridine-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; quinoline-2, 8-diyl; isoquinolin-1,3-diyl; isoquinolin-1,4-diyl; pyrazol-1,3-diyl; pyrazole-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-cyclononanes; 1,4-diaza-7-oxa-cyclononanes; 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-ylenes; 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-piperazine-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-ylidenes; 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-ylidenes; 1,4-diaza-7-thia-cyclonone-1,4-ylene; 1,4-diaza-7-thia-cyclonon-1,2-ylene; 1,4-diaza-7-thia-cyclone-2,3-ylene; 1,4-diaza-7-thia-cyclonon-6,8-ylene; 1,4-diaza-7-thia-cyclonone-2,2-ylidenes; 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-ylidenes; 1,4,7-trithia-cyclonon-2,3-ylene; 1,4,7-trithia-cyclonone-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 C 1 -C 8 -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; Cl-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; Cl-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; Cl-C6-alkyl-C6H5 and amine (to give amide) selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; Cl-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 -SiR3 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; CLC6-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 -OSiR3 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; CLC6-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

• alkyl: lineare und verzweigte C 1-C6-alkyl,
• langkettige Alkyle: lineare und verzweigte C5-C10 alkyl, vorzugsweise C6-C8 alkyle
• alkenyl: C3-C6-alkenyl,
• cycloalkyl: C6-C8-cycloalkyl,
• alkoxy: Cl-C4-alkoxy,
• langkettig Alkoxy: lineare und verzweigte C5-C10 alkoxy, vorzugsweise lineare C6-C8 alkoxy
• alkylene: ausgewählt aus der Gruppe enthaltend: methylene; 1,2-ethylene; 1,3-propylene; butan-2-ol-1,4-diyl; 1,4-butylene; cyclohexane-1,1-diyl; cyclohexan-1,2-diyl; cyclohexan-1,4-diyl; cyclopentane-1,1-diyl; und cyclopentan-1,2-diyl,
• aryl: ausgewählt aus der Gruppe enthaltend: phenyl; biphenyl; naphthyl; anthracenyl; und phenanthrenyl,
• arylene: ausgewählt aus der Gruppe enthaltend: 1,2-phenylene; 1,3- phenylene; 1,4-phenylene; 1,2-naphtalenylene; 1,4-naphtalenylene; 2,3- naphtalenylene und 1-hydroxy-2,6-phenylene,
• heteroaryl: ausgewählt aus der Gruppe enthaltend: pyridinyl; pyrimidinyl; chinoninyl; pyrazolyl; triazolyl; isochinoninyl; imidazolyl; und oxazolidinyl, wobei das Heteroaryl mit der Verbindung über jedes Atom im Ring des ausgewählten Heteroaryls verbunden sein kann,
• heteroarylene: ausgewählt aus der Gruppe enthaltend: pyridin 2,3-diyl; pyridin-2,4-diyl; pyridin-2,6-diyl; pyridin-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; isoquinolin-1,3-diyl; isoquinolin-1,4-diyl; pyrazol-3,5-diyl; und imidazole-2,4-diyl,
• heterocycloalkyl: ausgewählt aus der Gruppe enthaltend: 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; und piperazinyl, wobei das Heteroaryl mit der Verbindung über jedes Atom im Ring des ausgewählten Heteroaryls verbunden sein kann
• heterocycloalkylene: ausgewählt aus der Gruppe enthaltend: piperidin-2,6-ylene; 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-cyclonon-1,4 ylene; 1,4-diaza-7-thia-cyclonon-2,3-ylene; 1,4-diaza-7-thiein cyclonon-2,2-ylidene; 1,4-diaza-7-oxa-cyclonon-1,4-ylene; 1,4 diaza-7-oxa-cyclonon-2,3-ylene;1,4-diaza-7-oxa-cyclonon-2,2- ylidene; 1,4-dioxan-2,6-ylene; 1,4-dioxan-2,2-ylidene; tetrahydropyran-2,6-ylene; tetrahydropyran-2,5-ylene; und tetrahydropyran- 2,2-ylidene, ein -C1-C6-alkyl-heterocycloalkyl, wobei das Heterocycloalkyl ausgewählt aus der Gruppe enthaltend: 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; und pyrrolidinyl, 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; und benzyl,
• halogen: ausgewählt aus der Gruppe enthaltend: F und Cl,
• sulphonate: die Gruppe -S(O)₂OR, wobei R ausgewählt ist aus: Wasserstoff; Cl- C6-alkyl; Na; K; Mg; und Ca,
• sulphate: die Gruppe -OS(O)₂OR, wobei R ausgewählt ist aus: Wasserstoff; Cl- C6-alkyl; Na; K; Mg; und Ca,
• sulphone: die Gruppe -S(O)2R, wobei R ausgewählt ist aus: Wasserstoff; C1-C6- alkyl; benzyl und amine ausgewählt aus der Gruppe: -NR'2, wobei jedes R' unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; und benzyl,
• carboxylat: die Gruppe -C(O)OR, wobei R ausgewählt ist aus Wasserstoff; Na; K; Mg; Ca; C1-C6-alkyl; und benzyl,
• carbonyl: die Gruppe: -C(O)R, wobei R ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; benzyl und amine ausgewählt aus der Gruppe: -NR'2, wobei jedes R' unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; und benzyl,
• phosphonate: die Gruppe -P(O) (OR)2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; benzyl; Na; K; Mg; und Ca,
• phosphate: die Gruppe -OP(O) (OR)2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; benzyl; Na; K; Mg; und Ca,
• phosphine: die Gruppe -P(R)2, wobei jedes R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; und benzyl,
• phosphine oxid: die Gruppe -P(O)R2, wobei R unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; benzyl und amine ausgewählt aus der Gruppe: -NR'2, wobei jedes R' unabhängig ausgewählt ist aus: Wasserstoff; C1-C6-alkyl; und benzyl.
• 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, methyl, halogen und n ist von 5 bis 50, bevorzugt 10 bis 25.
• M, M_n (n ist eine ganze Zahl) : Metalle, wobei zwei Metalle M unabhängig voneinander ausgewählt sind, wenn nicht anders angezeigt.

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

• alkyl: linear and branched C 1 -C 6 -alkyl,
• long-chain alkyls: linear and branched C5-C10 alkyl, preferably C6-C8 alkyl
• alkenyl: C3-C6 alkenyl,
• cycloalkyl: C6-C8-cycloalkyl,
• alkoxy: Cl-C4-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-phenylenes; 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-ylene; 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 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 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; and benzyl,
• halogen: selected from the group comprising: F and Cl,
• sulphonates: the group -S (O) ₂ OR, where R is selected from: hydrogen; Cl-C6-alkyl; N / A; K; mg; and Ca,
• sulphate: the group -OS (O) ₂ OR, where R is selected from: hydrogen; Cl-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.
• polyethers: 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

• R¹ bis R³ 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.)
• R⁴ bis R⁷ 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 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.)
• und R¹ bis R⁷ so substituiert sein können, dass sich wahlweise zwischen R² und R³, R¹ und R²/R³ oder R²/R³ und R⁷ oder R⁶ und R⁷ oder R⁵ und R⁶ oder R⁴ und R⁵ ein Ring bildet.

According 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 to R ^3, independently of one another, are alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl, halo-ketoalkyl Silylalkyl, silylalkyloxy, where suitable radicals include one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO -, -COO-, -OCO-, -OCO-O-, -SO2-, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C = C- can be replaced in such a way in 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 (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH ₂ -H .)
• R ⁴ to R ⁷ independently of one another are hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl , Halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals include 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- may 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 groups in the sense of CH ₂ -H understood.)
• and R ¹ to R ^{7 may} be substituted to optionally between R ² and R ³ , R ¹ and R ² / R ³ or R ² / R ³ and R ⁷ or R ⁶ and R ⁷ or R ⁵ and R ⁶ or R ⁴ and R ^{5 forms} a ring.

These two previous N-heterocyclic carbene ligands are particularly preferred.

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.

According 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 radicals 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 each other, also optional with aryl or heteroaryl preferred 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.)
• 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 suitable radicals include one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO -, -COO-, -OCO-, -OCO-O-, -SO2-, -S-CO-, -CO-S-, -CY ¹ = CY ² or -C = C- can be replaced in such a way in 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 (terminal CH ₃ groups are understood as CH ₂ groups in the sense of CH 2 -H).
• 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.

wobei R³ und R⁴ wie beim vorigen Katalysator 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 defined as in the previous catalyst, R ⁵ and R ⁶ independently of one another are hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene, 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-, -SO2-, -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 one Single or double bond can be.

wobei R³, R⁴ und R⁵ wie beim vorigen Katalysator 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 defined as in the previous catalyst.

• 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) where 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 each 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 include 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- replaced can be such 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).

wobei R⁷ und R⁹ wie beim vorigen Katalysator definiert sind und X₁ und X₂ unabhängig voneinander O, NH oder CH₂ sein können.
Gemäß einer bevorzugten Ausführungsform der Erfindung umfasst der Katalysator am Rhodium noch mindestens einen weiteren Liganden, bevorzugt sind dabei labile Liganden. Darunter werden Liganden verstanden, deren Bindung zum Rhodium so schwach sind, dass sie ggf. im Verlauf der Reaktion zumindest temporär nicht mehr an das Rhodium gebunden 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 ⁷ and R ⁹ are defined as in the previous catalyst 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 further ligand on rhodium, preference being given to labile ligands. These are understood to mean ligands whose bonding to the rhodium is so weak that, if appropriate, they are at least temporarily not bound to the rhodium in the course of the reaction.

Preferred such labile ligands are dialkens, preferably COD, or norbornadiene, or alternatively to dialkenene, two ethylenes. Further possible ligands are carbonyl compounds, two chloride compounds, acetylacetonate, hydride ligands, halogen ligands, in particular chloride, or two phosphine compounds.

Preferably, the amount of catalyst before the reaction starts from ≥0.001 mol% to ≤10 mol% (based on the aromatic precursor substance at the beginning of the reaction), more preferably ≥0.05 mol% to ≤5 mol%, further preferably ≥0.1 mol% to ≤3 mol%, and most preferably ≥0.2 mol% to ≥1 mol%. It has been found that even with these relatively small amounts of catalyst, nevertheless, the reaction can often be carried out in high yield.

Preferably, the process is carried out in an organic solvent, have proven particularly useful in practice (and are therefore preferred): methanol, THF, 2-methyl-THF, 1,4-dioxane or mixtures of these solvents. Particularly preferred are THF and 2-methyl-THF.

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 ≥50 ° C, most preferably room temperature, ie ≥20 ° C to ≥40 ° C

In the event that gaseous hydrogen is used as the reducing agent, the preferred H 2 pressure (at the beginning of the reaction) is ≥3 bar, more preferably ranges from ≥10 bar to ≤ 150 bar.

The reaction is preferably carried out for a reaction time of ≥3h to ≤2d, particularly preferred reaction times are ≥5h to ≤ 30h.

Preferably, the reaction is carried out in the presence of an additive selected from the group boranes and silanes. It has been found that so often the yield can be increased even further.

The additive is preferably used in a ratio to the precursor substance of ≥ 0.1: 1 to ≦ 10: 1 (mol: mol), preferably ≥ 1: 1 to ≦ 4: 1 (mol: mol).

The additive is either a borane or a silane, with boranes being preferred.

Preferred boranes are dialkyl borohydrides and / or dioxaborolanes, with dioxaborolanes being preferred. The additive is preferably selected from the group comprising pinacolborane (4,4,5,5-tetramethyl-1,3,2-dioxaborolane), catecholborane, 9-BBN.

Preferred silanes are silanes of the structure R ¹ R ² SiH ₂ , where R ¹ and R ^{2 are selected} independently of one another from alkyl or aryl. R ¹ is preferably alkyl and R ^{2 is} aryl.

Preferably, the reaction is carried out in the presence of a Lewis acid, preferably a Lewis acid, which has dehydrating properties. It has been found that so often the yield can be increased even further. Preferred additives are selected from the group consisting of molecular sieve, preferably molecular sieve 4 Å and 3 Å, aluminum triisopropylate and mixtures thereof.

The ratio of additive to educt (before the reaction) of from ≥ 10 to ≦ 200 mg per 1 mmol of starting material is preferred

The above-mentioned and the claimed and described in the embodiments described components to be used in their size, shape design, material selection and technical design are not subject to any special conditions, so that the well-known in the field of application selection criteria can apply without restriction.

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.

General Procedure I:

A reaction-dried oven at 135 ° C (depending on the amount of solvent used either a 9 mL screw-cap vial (to 4 mL) or a 50 mL glass cylinder) filled with magnetic stirrer was allowed to cool under vacuum and pumped with activated 4Å molecular sieve (50 mg) catalyst ( 0.50 to 3.0 mol%) and solid starting material (1.0 mmol) - if the educt used is solid - filled in air. The atmosphere in the vial was exchanged with argon via a septum (3 x vacuum / argon cycle). After addition of tetrahydrofuran (1 mL, 1 M) and then gg. Liquid, over calcium hydride distilled starting material (1.0 mmol) - if the starting material used is liquid - and 4,4,5,5-tetramethyl-1,3, 2-dioxaborolane (HBpin, 2.0-4.0 mmol, 2.0-4.0 equiv.) Was transferred under argon to the vessel under argon atmosphere in a 150 mL steel autoclave under argon atmosphere, opening the autoclave cap during transfer and opening the autoclave Autoclave was held under an inert gas by means of an argon-flowed hose. The atmosphere in the autoclave was exchanged with hydrogen gas (3 × 10 bar hydrogen pressure / unloading cycle) before adjusting to 50 bar hydrogen pressure and the mixture was stirred for 24 h at the indicated temperature (25 ° C or 40 ° C) in a metal block (the specified temperature is that of the metal block). After carefully releasing the pressure, dichloromethane (0.5 mL) and trifluoroacetic anhydride (3.0 mmol, 3.0 equiv.) Were added to the reaction mixture and stirred at room temperature for 10 minutes. In an alternative procedure, di-tert-butyl dicarbonate (3.0 mmol, 3.0 equiv.) And triethylamine (3.0 mmol, 3.0 equiv.) Were added to the mixture and stirred at room temperature for 2 h. In both cases, the mixture was subsequently filtered through a glass frit, the residue being washed with ethyl acetate (2 × 5 ml). The combined filtrate was concentrated on a rotary evaporator and purified by column chromatography (silica gel, pentane / ethyl acetate or pentane / dichloromethane). The indicated diastereoselectivities were determined by GC MS, GC-FID or from the ¹⁹ F NMR spectrum immediately after the reaction. Based on the general procedure, the following fluorinated heterocyclic aliphatic compounds were prepared, in each case the following catalyst ((2- (2,6-diisopropylphenyl) -3,3-dimethyl-2-azaspiro [4.5] decan-1-ylidene) (cyclooctadienyl) rhodium (I) chloride) was used:

Katalysatorbeladung: 0,50 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 25 °C 81% Ausbeute (90% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). Die Reaktion wurde ebenfalls auf größerem Maßstab durchgeführt: 6,0 mmol Substrat Katalysatorbeladung: 0,50 mol% Konzentration: 1 M Menge an HBpin: 12 mmol Temp.: 25 °C 200 mg Molekularsieb 68% Ausbeute. 2 3,5-Difluorpyridin 1-(cis-3,5-Difluorpiperidin-1-yl)-2,2,2-trifluorethan-1-on Weißer Feststoff

Katalysatorbeladung: 0,50 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 79% Ausbeute, > 99:1 d.r. (95% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). Die Reaktion wurde ebenfalls auf größerem Maßstab durchgeführt: 6,0 mmol Substrat Katalysatorbeladung: 0,50 mol% Konzentration: 1 M Menge an HBpin: 12 mmol Temp.: 40 °C 200 mg Molekularsieb 89% Ausbeute, > 99:1 d.r. 3 3-Fluor-5-methylpyridin 2,2,2-Trifluor-1-(cis-3-fluor-5-methylpiperidin-1-yl)ethan-1-on Farbloses Öl Katalysatorbeladung: 2,0 mol%

Konzentration: 1 M Menge an HBpin: 2,0 mmol Temp.: 40 °C

75% Ausbeute, 88:12 d.r. (97% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 4 3-Fluor-2-methylpyridin 2,2,2-Trifluor-1-(cis-3-fluor-2-methylpiperidin-1-yl)ethan-1-on Farbloses Öl Katalysatorbeladung: 0,50 mol%

Konzentration: 1 M Menge an HBpin: 4,0 mmol

Temp.: 40 °C 77% Ausbeute, 95:5 d.r. (89% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 5 3-Fluor-4-methylpyridin 2,2,2-Trifluor- 1 -(cis-3-fluor-4-methylpiperidin-1-yl)ethan-1-on Farbloses Öl Katalysatorbeladung: 0,50 mol%

Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 85% Ausbeute, 95:5 d.r. (93% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 6 5-Fluor-2-methylpyridin 2,2,2-Trifluor-1-(5-fluor-2-methylpiperidin-1-yl)ethan-1-on Farbloses Öl 0,50 mmol Substrat

Katalysatorbeladung: 0,50 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 84% Ausbeute, 90:10 d.r. (95% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 7 3-Fluor-4,5-dimethylpyridin 2,2,2-Trifluor-1-(3-fluor-4,5-dimethylpiperidin-1-yl)ethan-1-on Farbloses Öl 0,50 mmol Substrat

Katalysatorbeladung: 2,0 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 70% Ausbeute, 95:5 d.r. 8 2-Butyl-3-fluorpyridin 1-(cis-2-Butyl-3-fluorpiperidin-1-yl)-2,2,2-trifluorethan-1-on Farbloses Öl 0,50 mmol Substrat

Katalysatorbeladung: 2,0 mol%

Konzentration: 1 M Menge an HBpin: 2,0 mmol Temp.: 40 °C 80% Ausbeute, 99:1 d.r. 9 4-(((tert-Butyldimethylsilyl)o xy)methyl)-3-fluorpyridin tert-Butyl cis-4-(((tert-butyldimethylsilyl)oxy) methyl)-3-fluorpiperidine-1-carboxylat Farbloses Öl Katalysatorbeladung: 2,0 mol% Konzentration: 1 M Menge an HBpin: 3,0 mmol

Temp.: 40 °C

85% Ausbeute, 95:5 d.r. (95% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 10 2-(((tert-Butyldimethylsilyl)oxy)methyl)-3-fluorpyridin tert-Butyl cis-2-(((tert-butyldimethylsil yl)oxy) methyl)-3-fluorpiperidine-1-carboxylat Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 0,50 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 84% Ausbeute, 99:1 d.r. 11 3-(((tert-Butyldimethylsilyl)o xy)methyl)-5-fluorpyridin 3-(((tert-Butyldimethylsil yl)oxy) methyl)-5-fluor-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin 0,50 mmol Substrat Katalysatorbeladung: 2,0 mol% Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 81% ¹⁹F NMR Ausbeute, 88:12

d.r. mit Hexafluorbenzol als internem Standard. 12 2-(((tert-Butyldimethylsilyl)o xy)methyl)-5-fluorpyridin tert-Butyl cis-2-(((tert-butyldimethylsil yl)oxy) methyl)-5-fluorpiperidin-1-carboxylat Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 2,0 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol

Temp.: 40 °C 94% Ausbeute, 97:3 d.r. 13 2-(((tert-Butyldimethylsilyl)o xy)methyl)-3,5-difluorpyridin tert-Butyl cis-2-(((tert-butyldimethylsil yl)oxy) methyl)-3,5-difluorpiperidin-1-carboxylat Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 2,0 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol

Temp.: 40 °C 73% Ausbeute, 99:1 d.r. 14 2-(2-((tert-Butyldimethylsilyl)o xy)ethyl)-5-fluorpyridin tert-Butyl-2-(2-((tert-butyldimethylsil yl)oxy) ethyl)-5-fluoropiperidin-1-carboxylat Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 0,50 mol% Konzentration: 1 M

Menge an HBpin: 2,0 mmol

Temp.: 40 °C 92% Ausbeute, 95:5 d.r. 15 4-(((tert-Butyldimethylsilyl)o xy)methyl)-3-fluor-5-methylpyridin 4-(((tert-Butyldimethylsil yl)oxy) methyl)-3-fluor-5-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin 0,50 mmol Substrat Katalysatorbeladung: 2,0 mol% Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 91% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard.

16 tert-Butyl((5-fluorpyridin-2-yl)methyl)carbamat tert-Butyl((5-fluor-1-(2,2,2-trifluoroacetyl)piperidin -2-yl)methyl)carbamat Weißer Feststoff 0,50 mmol Substrat Katalysatorbeladung: 3,0 mol%

Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 61% Ausbeute, 99:1 d.r. (95% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 17 tert-Butyl((3-fluoropyridin-2-yl)methyl)carbamate tert-Butyl-2-(((tert-butoxycarbonyl)amino) methyl)-3-fluoropiperidine-1-carboxylate Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 3,0 mol%

Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 88% Ausbeute, 99:1 d.r. 18 3-Fluor-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin cis-3-Fluor-1,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin 0,50 mmol Substrat Katalysatorbeladung: 0,50 mol% Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 70% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard. 19 tert-Butyl-5-fluor-1H-pyrrolo[2,3-b]pyridin-1-carboxylat tert-Butyl cis-5-fluor-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octahydro-1H-pyrrolo[2,3-b]pyridin- 1-carboxylat 0,50 mmol Substrat Katalysatorbeladung: 3,0 mol% Konzentration: 1 M Menge an HBpin: 2,0 mmol

Temp.: 40 °C 64% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard.

20 3-((tert-Butyldimethylsilyl)o xy)-5-fluorpyridin cis-3-((tert-Butyldimethylsil yl)oxy) -5-fluor-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidin 0,50 mmol Substrat Katalysatorbeladung: 3,0 mol% Konzentration: 0.25 M

Menge an HBpin: 1,0 mmol Temp.: 40 °C 70% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard.

21 3-Fluor-4-(phenylthio)pyridin 2,2,2-Trifluor-1-(5-fluor-4-(phenylthio)-3,6-dihydropyridin-1(2H)-yl)ethan-1-on Farbloses Öl 0,25 mmol Substrat

Katalysatorbeladung: 3,0 mol% Konzentration: 1 M

Menge an HBpin: 1,0 mmol Temp.: 40 °C 41% Ausbeute. 22 3-Fluor-4-(trimethylsilyl)pyridin 2,2,2-Trifluor-1-(3-fluor-4-(trimethylsilyl)piperidin -1-yl)ethan-1-on Farbloses Öl 0,50 mmol Substrat Katalysatorbeladung: 2,0 mol%

Konzentration: 1 M

Menge an HBpin: 2,0 mmol Temp.: 40 °C 71% Ausbeute, 99:1 d.r. (83% ¹⁹F NMR Ausbeute mit Hexafluorbenzol als internem Standard). 23 3-Fluoroquinolin 3-Fluor-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)decahydroquinolin 0,25 mmol Substrat

Katalysatorbeladung: 3,0 mol% Konzentration: 1 M Menge an HBpin: 1,0 mmol

Temp.: 40 °C 95% ¹⁹F NMR Ausbeute, 91:9 d.r. mit Hexafluorbenzol als internem Standard. The results are given in the following table: Example No. reactant product Conditions and yield 1 3-fluoropyridine 2,2,2-trifluoro-1- ethan-1-one (3-fluoro-piperidin-1-yl) Colorless oil

Catalyst loading: 0.50 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 25 ° C 81% yield (90% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). The reaction was also carried out on a larger scale: 6.0 mmol substrate Catalyst loading: 0.50 mol% Concentration: 1 M Amount of HBpin: 12 mmol Temp .: 25 ° C 200 mg molecular sieve 68% yield. 2 3,5-difluoropyridine 1- (cis-3,5-difluoropiperidine-1-yl) -2,2,2-trifluoroethane-1-one White solid

Catalyst loading: 0.50 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 79% yield,> 99: 1 dr (95% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). The reaction was also carried out on a larger scale: 6.0 mmol substrate Catalyst loading: 0.50 mol% Concentration: 1 M Amount of HBpin: 12 mmol Temp .: 40 ° C 200 mg molecular sieve 89% yield,> 99: 1 dr 3 3-fluoro-5-methylpyridine (Cis-3-fluoro-5-methyl-piperidin-1-yl) ethan-1-one 2,2,2-trifluoro-1- Colorless oil Catalyst loading: 2.0 mol%

Concentration: 1 M Amount of HBpin: 2.0 mmol Temp .: 40 ° C

75% yield, 88:12 dr (97% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 4 3-fluoro-2-methylpyridine (Cis-3-fluoro-2-methyl-piperidin-1-yl) ethan-1-one 2,2,2-trifluoro-1- Colorless oil Catalyst loading: 0.50 mol%

Concentration: 1 M Amount of HBpin: 4.0 mmol

Temp .: 40 ° C 77% yield, 95: 5 dr (89% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 5 3-fluoro-4-methylpyridine 2,2,2-trifluoro-1 - (cis-3-fluoro-4-methyl-piperidin-1-yl) -ethan-1-one Colorless oil Catalyst loading: 0.50 mol%

Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 85% yield, 95: 5 dr (93% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 6 5-fluoro-2-methylpyridine 2,2,2-trifluoro-1- ethan-1-one (5-fluoro-2-methyl-piperidin-1-yl) Colorless oil 0.50 mmol substrate

Catalyst loading: 0.50 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 84% yield, 90:10 dr (95% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 7 3-fluoro-4,5-dimethylpyridine 2,2,2-trifluoro-1- ethan-1-one (3-fluoro-4,5-dimethyl-piperidin-1-yl) Colorless oil 0.50 mmol substrate

Catalyst loading: 2.0 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 70% yield, 95: 5 dr 8th 2-butyl-3-fluoropyridine 1- (cis-2-butyl-3-fluoro-piperidin-1-yl) -2,2,2-trifluoroethane-1-one Colorless oil 0.50 mmol substrate

Catalyst loading: 2.0 mol%

Concentration: 1 M Amount of HBpin: 2.0 mmol Temp .: 40 ° C 80% yield, 99: 1 dr 9 4 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoropyridine tert -Butyl cis-4 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoropiperidine-1-carboxylate Colorless oil Catalyst loading: 2.0 mol% Concentration: 1 M Amount of HBpin: 3.0 mmol

Temp .: 40 ° C

85% yield, 95: 5 dr (95% ¹⁹ F NMR yield with Hexafluorobenzene as an internal standard). 10 2 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoropyridine tert -Butyl cis-2 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoropiperidine-1-carboxylate Colorless oil 0.50 mmol substrate Catalyst loading: 0.50 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 84% yield, 99: 1 dr 11 3 - (((tert-butyldimethylsilyl) oxy) methyl) -5-fluoropyridine 3 - (((tert-butyldimethylsilyl) oxy) methyl) -5-fluoro-1- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) piperidine 0.50 mmol substrate Catalyst loading: 2.0 mol% Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 81% ¹⁹ F NMR yield, 88:12

dr with hexafluorobenzene as internal standard. 12 2 - (((tert-butyldimethylsilyl) oxy) methyl) -5-fluoropyridine tert -Butyl cis-2 - (((tert-butyldimethylsilyl) oxy) methyl) -5-fluoropiperidine-1-carboxylate Colorless oil 0.50 mmol substrate Catalyst loading: 2.0 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 94% yield, 97: 3 dr 13 2 - (((tert-butyldimethylsilyl) oxy) methyl) -3,5-difluoropyridine tert -Butyl cis-2 - (((tert-butyldimethylsilyl) oxy) methyl) -3,5-difluoropiperidine-1-carboxylate Colorless oil 0.50 mmol substrate Catalyst loading: 2.0 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 73% yield, 99: 1 dr 14 2- (2 - ((tert-butyldimethylsilyl) oxy) ethyl) -5-fluoropyridine tert -Butyl 2- (2 - ((tert-butyldimethylsilyl) oxy) ethyl) -5-fluoropiperidine-1-carboxylate Colorless oil 0.50 mmol substrate Catalyst loading: 0.50 mol% Concentration: 1 M

Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 92% yield, 95: 5 dr 15 4 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoro-5-methylpyridine 4 - (((tert-butyldimethylsilyl) oxy) methyl) -3-fluoro-5-methyl-1- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) piperidine 0.50 mmol substrate Catalyst loading: 2.0 mol% Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 91% ¹⁹ F NMR yield with Hexafluorobenzene as an internal standard.

16 tert-butyl ((5-fluoropyridin-2-yl) methyl) carbamate tert -Butyl ((5-fluoro-1- (2,2,2-trifluoroacetyl) piperidin-2-yl) methyl) carbamate White solid 0.50 mmol substrate Catalyst loading: 3.0 mol%

Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 61% yield, 99: 1 dr (95% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 17 tert-butyl ((3-fluoropyridin-2-yl) methyl) carbamate tert -Butyl 2 - (((tert-butoxycarbonyl) amino) methyl) -3-fluoropiperidine-1-carboxylate Colorless oil 0.50 mmol substrate Catalyst loading: 3.0 mol%

Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 88% yield, 99: 1 dr 18 3-fluoro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine cis-3-fluoro-1,5-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) piperidine 0.50 mmol substrate Catalyst loading: 0.50 mol% Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 70% ¹⁹ F NMR yield with Hexafluorobenzene as an internal standard. 19 tert-butyl-5-fluoro-1H-pyrrolo [2,3-b] pyridine-1-carboxylate tert -Butyl cis-5-fluoro-7- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) octahydro-1H-pyrrolo [2,3-b] pyridine-1 carboxylate 0.50 mmol substrate Catalyst loading: 3.0 mol% Concentration: 1 M Amount of HBpin: 2.0 mmol

Temp .: 40 ° C 64% ¹⁹ F NMR yield with hexafluorobenzene as internal standard.

20 3 - ((tert-butyldimethylsilyl) oxy) -5-fluoropyridine cis-3 - ((tert-butyldimethylsilyl) oxy) -5-fluoro-1- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) piperidine 0.50 mmol substrate Catalyst loading: 3.0 mol% Concentration: 0.25 M

Amount of HBpin: 1.0 mmol Temp .: 40 ° C 70% ¹⁹ F NMR yield with hexafluorobenzene as internal standard.

21 3-fluoro-4- (phenylthio) pyridine 2,2,2-trifluoro-1- (5-fluoro-4- (phenylthio) -3,6-dihydropyridin-1 (2H) -yl) ethane-1-one Colorless oil 0.25 mmol substrate

Catalyst loading: 3.0 mol% Concentration: 1 M

Amount of HBpin: 1.0 mmol Temp .: 40 ° C 41% yield. 22 3-fluoro-4- (trimethylsilyl) pyridine 2,2,2-Trifluoro-1- (3-fluoro-4- (trimethylsilyl) piperidin-1-yl) ethan-1-one Colorless oil 0.50 mmol substrate Catalyst loading: 2.0 mol%

Concentration: 1 M

Amount of HBpin: 2.0 mmol Temp .: 40 ° C 71% yield, 99: 1 dr (83% ¹⁹ F NMR yield with hexafluorobenzene as internal standard). 23 3-Fluoroquinolin 3-fluoro-1- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) decahydroquinolin 0.25 mmol substrate

Catalyst loading: 3.0 mol% Concentration: 1 M Amount of HBpin: 1.0 mmol

Temp .: 40 ° C 95% ¹⁹ F NMR yield, 91: 9 dr with hexafluorobenzene as internal standard.

Furthermore, using the above procedure I, various catalysts were tested whose structure and yield (determined according to NMR) are indicated below:

Furthermore, further additives were tested whose structure and yield are shown below:

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 "comprising" 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)

A process for producing fluorinated heterocyclic aliphatic compounds comprising the step of hydrogenating a heteroaromatic fluorochemical precursor with a catalyst comprising at least one rhodium atom in the presence of a reducing agent. Method according to Claim 1 wherein the catalyst comprises rhodium with at least one labile ligand. Method according to Claim 2 wherein the labile ligands are selected from the group consisting of alkenes, cyclic bis-alkenes, halides, triflates, acetonitrile, weakly coordinating anions such as tetrafluoroborate or phosphines Method according to one of Claims 1 to 3 wherein the catalyst comprises at least one N-heterocyclic carbene ligand. Method according to one of Claims 1 to 4 wherein the hydrogenation is carried out in the presence of an additive selected from the group of boranes and silanes. Method according to one of Claims 1 to 5 wherein the hydrogenation is carried out in the presence of a Lewis acid. Method according to one of Claims 1 to 6 , wherein the amount of catalyst before the start of the reaction from ≥0.05 mol% to ≤5 mol% (based on the aromatic precursor substance at the beginning of the reaction). Method according to one of Claims 1 to 7 wherein the process is carried out in an organic solvent. Method according to one of Claims 1 to 8th , wherein the process is carried out at a temperature of ≥0 ° C. Method according to one of Claims 1 to 9 , wherein the method is carried out using gaseous hydrogen as a reducing agent and the H2 pressure (at the beginning of the reaction) is ≥10 bar.