DE102004036068B4 - Process for hydrogenation - Google Patents

Abstract

A process for preparing a compound of formula IA or IB wherein d, f and i are 0; b and g are 0 or 1; c and h0 are or 1; e and j1 are; A11, A14, X21 and A24 are a 1,4-cyclohexylene radical or a 1,4-phenylene radical mono- or polysubstituted by halogen, A12 and A22 are an unsubstituted 1,4-cyclohexylene radical, provided b or g is 1; A13 and A23 are an unsubstituted 1,4-cyclohexylene radical or an unsubstituted 1 or mono- or polysubstituted by halogen, 4-phenylene radical, provided that c or h is 1;A15 and A25 are an unsubstituted 1,4-phenylene radical or mono- or polysubstituted by halogen; R11 is hydrogen, an unsubstituted or mono- or poly-substituted identically or differently substituted alkyl radical having up to 8 carbon atoms, where in one or more CH2 groups in these radicals can also be replaced independently by -O- or -O-CO- in such a way that heteroatoms (-O-) are not linked directly to one another, where R11 is not hydrogen if both a and b are zero and Z12 is a single bond; Y11 and Y21 are an unsubstituted or mono- or polysubstituted F alkyl or alkoxy radical having 1 to 8 carbon atoms, an unsubstituted or substituted aralkyl or aralkyl-O radical having 7 to 12 carbon atoms, F, Cl, Br or CN Z11, Z12, Z15, Z21, Z22, and Z25 are a single bond, Z13 and Z23 are a single bond or -CO-O-; Z14 and Z24 are a single bond or -CF2O- if c and h are 1, respectively; andW-O-;characterized in that a compound of the formula IIA or a compound of the formula IIBwhereinR21is hydrogen, an unsubstituted or mono- or polysubstituted, identically or differently substituted alkyl radical having 1 to 8 carbon atoms, in which radicals one or more CH2- Groups can be independently replaced by -CH=CH-, -O- or -O-CO- such that heteroatoms (-O-) are not linked directly to each other, where R21 is not hydrogen when f and g are both zero and Z22 means a single bond, and the other parameters are as defined under formulas IA and IB.

Description

The present invention relates to a process for the hydrogenation of cyclohexene and dihydropyran derivatives and a composition comprising a cyclohexene or dihydropyran derivative and a transition metal complex. In particular, the invention relates to a process for the trans-selective hydrogenation of cyclohexene and dihydropyran derivatives.

Compounds that have a cyclohexane ring or a tetrahydropyran ring as a central part of the molecule play an important role in organic chemistry, for example as ingredients of natural or synthetic flavorings, drugs or mesogenic or liquid-crystalline compounds or as precursors for the synthesis of these useful substances.

In particular, mesogenic or liquid-crystalline compounds with a cyclohexane ring or tetrahydropyran ring often have (mesogenic) substituents, rings and/or ring systems in the 1- and 4-position of the cyclohexane ring or in the 2- and 5-position of the tetrahydropyran ring. It is usually desirable for these residues to be oriented trans to one another in the 1 and 4 positions or in the 2 and 5 positions, so that they can assume a bisequatorial conformation with the formation of an elongated molecular shape that is important for the mesogenic properties.

The targeted preparation of these trans-1,4-disubstituted cyclohexane or trans-2,5-disubstituted tetrahydropyran derivatives has hitherto only been possible with considerable technical effort and with moderate yields: the 1,4-disubstituted cyclohexane derivatives are frequently obtained from the corresponding 1,4-disubstituted Cyclohex-1-ene derivatives by catalytic hydrogenation over a heterogeneous transition metal catalyst such as Raney nickel ( EP 0 415 090 A1 ), palladium ( EP 1182186 A2 ) or platinum - usually bound to a carrier. In the most favorable case, a mixture of stereoisomers of cis- and trans-1,4-disubstituted cyclohexane derivatives, in which the cis isomer forms the main product, is often obtained in poor yields; often even the undesired cis isomer is the only isolable product of the catalytic hydrogenation. Thus, a complex separation of the isomer mixture, for example by means of crystallization and / or chromatography methods and / or as a further reaction step, the isomerization (with subsequent purification) of the cis into the trans compound is required under comparatively drastic conditions, for example with a strong base such as potassium tert-butylate. In many cases, this is also associated with poor yields.

- die ihrerseits sehr gut beispielsweise durch Eninbeziehungsweise ringschließende Kreuz-Metathese-Verfahren aus geeignet substituierten Eninen oder Dienen (vgl. die deutschen Patentanmeldungen DE 10324348.8 beziehungsweise DE 10324312.7 ) zugänglich sind. Hier ist außerdem zu bemerken, dass bei der Isomerisierung des üblicherweise nach der heterogen katalysierten Hydrierung erhaltenen cis/trans-Isomerengemischs durch teilweise Zersetzung der Tetrahydropyranverbindungen die Ausbeute des gewünschten trans-Produkts deutlich vermindert werden kann.The same applies to the production of 2,5-disubstituted tetrahydropyran derivatives from the corresponding dihydropyran derivatives with an endocyclic CC double bond in the 4-position

- Which in turn are very good, for example, by enyne or ring-closing cross-metathesis processes from suitably substituted enynes or dienes (cf. the German patent applications DE 10324348.8 respectively DE 10324312.7 ) are accessible. It should also be noted here that in the isomerization of the cis/trans isomer mixture usually obtained after the heterogeneously catalyzed hydrogenation, the yield of the desired trans product can be significantly reduced by partial decomposition of the tetrahydropyran compounds.

The hydrogenation of alkenes over homogeneous transition metal catalysts, in particular of cyclic alkenes over rhodium complexes in the presence of phosphine ligands, has been known for some time. See. AS Hussey et al., Journal of the American Chemical Society, 1969, Vol. 91, No. 3, pp. 672-675 ; AS Hussey et al., Journal of Organic Chemistry, 1970, Vol. 35, No. 3, pp. 643 - 647 ; R. Grzybek in "Catalytic olefin hydrogenation with the application of a new water-soluble rhodium catalyst" In: Reaction Kinetics and Catalysis Letters, 1996, Volume 58, No. 2, pp. 315 - 322 . The stereoisomerism of the hydrogenation products of substituted cyclohexanes is discussed: Y. Takagi et al., Journal of Molecular Catalysis, Vol. 29, 1985, pp. 41-54 and A. Yanagawa et al., Journal of Molecular Catalysis, Vol. 29, 1985, pp. 41-54 .

It is therefore an object of the present invention to provide a process for the preparation of 1,4-disubstituted cyclohexane derivatives [not according to the claims] and 2,5-disubstituted tetrahydropyran derivatives which better obtain the desired trans isomers, in particular with high selectivity and with a high overall yield, makes accessible.

worin

a, b, c, d und e

unabhängig voneinander 0 oder 1 sind, wobei e 1 ist, wenn W für -CH₂- steht;

A11, A12, A13, A14, A15

unabhängig voneinander einen 1,4-Cyclohexylenrest, in dem auch eine oder zwei nicht benachbarte CH₂-Gruppen durch -O- und/oder -S- ersetzt sein können, oder einen 1,4-Phenylenrest, in dem auch eine oder zwei nicht benachbarte =CH-Gruppen durch =N- ersetzt sein können, oder einen Naphthalin-2,6-diyl- oder 1,2,3,4-Tetrahydronaphthalin-2,6-diylrest darstellen, wobei diese Reste unsubstituiert oder mit Halogen oder CN einfach oder mehrfach gleich oder verschieden substituiert sind, oder einen 1,3-Cyclobutylen-, Piperidin-1,4-diyl- oder Decahydro-naphthalin-2,6-diylrest bedeuten;

R11

Wasserstoff, einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen bedeutet, wobei in diesen Resten auch eine oder mehrere CH₂-Gruppen unabhängig voneinander so durch -C≡C-, -S-, -O-, -CO-, -COO-, -O-CO- oder -O-CO-O- ersetzt sein können, dass Heteroatome (-S-, -O-) nicht direkt miteinander verknüpft sind, wobei R¹¹ nicht Wasserstoff bedeutet, wenn zugleich a und b null sind und Z¹² eine Einfachbindung bedeutet;

W

-CH₂- oder -O- bedeutet;

Y11

Wasserstoff, Halogen, -NCS, -SCN, -SF₅, -CN, einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden mit Halogen oder -CN substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen oder einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden mit Halogen, Nitro, Alkanyl, Alkoxy, -NH₂ oder -N(Alkanyl)₂ substituierten Aralkylrest mit 7 bis 16 Kohlenstoffatomen bedeutet, wobei in diesen Resten auch eine oder mehrere CH₂-Gruppen unabhängig voneinander so durch -C≡C-, -S-,-S(O)-, -S(O)₂-, -O-, -CO-, -COO-, -O-CO- oder -O-CO-O- ersetzt sein können, dass Heteroatome (-S-, -O-) in der Kette nicht direkt miteinander verknüpft sind;

Z11, Z13, Z14 und Z15

unabhängig voneinander eine Einfachbindung, -CH₂CH₂-, -CF₂CF₂-, -CH₂CF₂-, -CF₂CH₂-, -CFH-CFH-, -C=C-, -CH₂O-, -OCH₂-, -CF₂O-, -OCF₂-, -COO- oder -O-CO-bedeuten;

Z12

eine Einfachbindung, -CH₂CH₂-, -C---C-, -CH₂O-, -OCH₂-, -COO- oder -O-CO- bedeutet;

das dadurch gekennzeichnet ist, dass
eine Verbindung der Formel IIA beziehungsweise der Formel IIB

worin

f, g, h, i und j

unabhängig voneinander 0 oder 1 sind, wobei j 1 ist, wenn W für -CH₂- steht;

A21, A22, A23, A24, A25

unabhängig voneinander einen 1,4-Cyclohexylenrest, in dem auch eine oder zwei nicht benachbarte CH₂-Gruppen durch -O- und/oder -S- ersetzt sein können, oder einen 1,4-Phenylenrest, in dem auch eine oder zwei nicht benachbarte =CH-Gruppen durch =N- ersetzt sein können, oder einen Naphthalin-2,6-diyl- oder 1,2,3,4-Tetrahydronaphthalin-2,6-diylrest darstellen, wobei diese Reste unsubstituiert oder mit Halogen oder CN einfach oder mehrfach gleich oder verschieden substituiert sind, oder einen 1,3-Cyclobutylen-, Piperidin-1,4-diyl- oder Decahydro-naphthalin-2,6-diylrest bedeuten;

R21

Wasserstoff, einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen bedeutet, wobei in diesen Resten auch eine oder mehrere CH₂-Gruppen unabhängig voneinander so durch -CH=CH-, -C=C-, -S-, -O-, -CO-, -COO-, -O-CO- oder -O-CO-O- ersetzt sein können, dass Heteroatome (-S-, -O-) nicht direkt miteinander verknüpft sind, wobei R²¹ nicht Wasserstoff bedeutet, wenn f und g zugleich null sind und Z²² eine Einfachbindung bedeutet;

W

-CH₂- oder -O- bedeutet;

Y21

Wasserstoff, Halogen, -NCS, -SCN, -SF₅, -CN, einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden mit Halogen oder -CN substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen oder einen unsubstituierten oder einfach oder mehrfach gleich oder verschieden mit Halogen, Nitro, Alkanyl, Alkoxy, -NH₂ oder -N(Alkanyl)₂ substituierten Aralkylrest mit 7 bis 16 Kohlenstoffatomen bedeutet, wobei in diesen Resten auch eine oder mehrere CH₂-Gruppen unabhängig voneinander so durch -CH=CH-, -C≡C-, -S-, -S(O)-, -S(O)₂-, -O-, -CO-, -COO-, -O-CO- oder -O-CO-O-ersetzt sein können, dass Heteroatome (-S-, -O-) in der Kette nicht direkt miteinander verknüpft sind;

Z21, Z23, Z24 und Z25

unabhängig voneinander eine Einfachbindung, -CH=CH-, -CH₂CH₂-, -CF₂CF₂-, -CH₂CF₂-, -CF₂CH₂-, -CFH-CFH-, -C≡C-, -CH₂O-, -OCH₂-, -CF₂O-, -OCF₂-, -COO-oder -O-CO- bedeuten;

Z22

eine Einfachbindung, -CH=CH-, -CH₂CH₂-, -C=C-, -CH₂O-, -OCH₂-, -COO- oder -O-CO- bedeutet;

in Gegenwart eines mit einem oder mehreren gleichen oder verschiedenen Phosphinliganden stabilisierten Übergangsmetallkomplexes hydriert wird.This object is achieved by a process for preparing a compound of the formula IA or IB [partly not according to the claims]

wherein

a, b, c, d and e

are independently 0 or 1, with e being 1 when W is -CH ₂ -;

A11, A12, A13, A14, A15

independently of one another a 1,4-cyclohexylene radical in which one or two non-adjacent CH ₂ groups can also be replaced by -O- and/or -S-, or a 1,4-phenylene radical in which one or two are not adjacent =CH groups may be replaced by =N-, or represent a naphthalene-2,6-diyl or 1,2,3,4-tetrahydronaphthalene-2,6-diyl radical, these radicals being unsubstituted or having halogen or CN are substituted one or more times, identically or differently, or are a 1,3-cyclobutylene, piperidine-1,4-diyl or decahydro-naphthalene-2,6-diyl radical;

R11

is hydrogen, an unsubstituted or mono- or polysubstituted alkyl radical having 1 to 15 carbon atoms, where in these radicals one or more CH ₂ groups are independently represented by -C≡C-, -S-, -O-, -CO-, -COO-, -O-CO- or -O-CO-O- can be replaced, that heteroatoms (-S-, -O-) are not linked directly to one another, where R ¹¹ is not hydrogen if both a and b are zero and Z ¹² is a single bond;

W

-CH ₂ - or -O-;

Y11

Hydrogen, halogen, -NCS, -SCN, -SF ₅ , -CN, an alkyl radical having 1 to 15 carbon atoms which is unsubstituted or substituted once or more in the same or different ways by halogen or -CN, or an alkyl radical which is unsubstituted or substituted in the same or different ways by halogen , Nitro, alkanyl, alkoxy, -NH ₂ or -N(alkanyl) ₂ is a substituted aralkyl radical having 7 to 16 carbon atoms, in which radicals one or more CH ₂ groups are independently substituted by -C≡C-, -S -,-S(O)-, -S(O) ₂ -, -O-, -CO-, -COO-, -O-CO- or -O-CO-O- can be replaced that heteroatoms (- S-, -O-) are not directly linked to each other in the chain;

Z11, Z13, Z14 and Z15

independently a single bond, _{-CH 2} CH ₂ -, -CF ₂ CF ₂ -, -CH ₂ CF 2 -, -CF ₂ CH ₂ -, -CFH-CFH-, -C=C-, -CH ₂ O- , -OCH ₂ -, -CF ₂ O-, -OCF ₂ -, -COO- or -O-CO-;

Z12

a single bond, -CH ₂ CH ₂ -, -C---C-, -CH ₂ O-, -OCH ₂ -, -COO- or -O-CO-;

which is characterized in that
a compound of formula IIA or formula IIB

wherein

f, g, h, i and j

are independently 0 or 1, with j being 1 when W is -CH ₂ -;

A21, A22, A23, A24, A25

independently of one another a 1,4-cyclohexylene radical in which one or two non-adjacent CH ₂ groups can also be replaced by -O- and/or -S-, or a 1,4-phenylene radical in which one or two are not adjacent =CH groups may be replaced by =N-, or represent a naphthalene-2,6-diyl or 1,2,3,4-tetrahydronaphthalene-2,6-diyl radical, these radicals being unsubstituted or having halogen or CN are substituted one or more times, identically or differently, or are a 1,3-cyclobutylene, piperidine-1,4-diyl or decahydro-naphthalene-2,6-diyl radical;

R21

Hydrogen, an unsubstituted or singly or multiply identically or differently substituted alkyl radical having 1 to 15 carbon atoms, in which radicals one or more CH ₂ groups are independently represented by -CH=CH-, -C=C-, -S -, -O-, -CO-, -COO-, -O-CO- or -O-CO-O- can be replaced, that heteroatoms (-S-, -O-) are not linked directly to each other, where R ²¹ is not hydrogen when f and g are both zero and Z ²² is a single bond;

W

-CH ₂ - or -O-;

Y21

Hydrogen, halogen, -NCS, -SCN, -SF ₅ , -CN, an alkyl radical having 1 to 15 carbon atoms which is unsubstituted or substituted once or more in the same or different ways by halogen or -CN, or an alkyl radical which is unsubstituted or substituted in the same or different ways by halogen , Nitro, alkanyl, alkoxy, -NH ₂ or -N(alkanyl) ₂ is a substituted aralkyl radical having 7 to 16 carbon atoms, in which radicals one or more CH ₂ groups are independently substituted by -CH=CH-, -C ≡C-, -S-, -S(O)-, -S(O) ₂ -, -O-, -CO-, -COO-, -O-CO- or -O-CO-O- that heteroatoms (-S-, -O-) in the chain are not directly linked to each other;

Z21, Z23, Z24 and Z25

independently a single bond, -CH=CH-, -CH ₂ CH ₂ -, -CF ₂ CF ₂ -, -CH ₂ CF ₂ -, -CF ₂ CH ₂ -, -CFH-CFH-, -C≡C- , -CH ₂ O-, -OCH ₂ -, -CF ₂ O-, -OCF ₂ -, -COO- or -O-CO-;

Z22

a single bond, -CH=CH-, -CH ₂ CH ₂ -, -C=C-, -CH ₂ O-, -OCH ₂ -, -COO- or -O-CO-;

is hydrogenated in the presence of a stabilized with one or more identical or different phosphine ligand transition metal complex.

It is understood that in the process of the invention the compound of formula IA is formed from the compound of formula IIA and the compound of formula IB is formed from the compound of formula IIB. When reference is made below to compounds of the formula I, both compounds of the formula IA and compounds of the formula IB are meant; accordingly, "compounds of formula II" means both compounds of formula IIA and compounds of formula IIB.

The process according to the invention proceeds with good to very good overall conversion, which is generally above 90% and in many cases is greater than 95%. Surprisingly, this also applies to “large” molecules of the formula II with an extended molecular shape and several rings in the molecule. The desired trans isomer of the formula I is obtained in good to very good yields with good to very good trans selectivity. As a rule, the proportion of the trans product of formula I in the product mixture is more than 70% and in many cases more than 75%. The pure trans product of the formula I can be separated from the other products of the reaction, in particular from the cis isomer, in a simple manner after the reaction mixture has been worked up in the usual manner, usually by a single crystallization from a suitable solvent separated and then, for example, either used itself as a liquid-crystalline component in liquid-crystalline media or converted into other liquid-crystalline compounds with further functionalization or derivatization. In some cases it is observed that the main trans isomer product precipitates or crystallizes out of the reaction mixture.

In comparison, the heterogeneously catalyzed hydrogenation of compounds of formula II, for example with palladium on activated carbon, predominantly gives the respective undesired cis isomer of formula cis-I with typical cis selectivities of 60 to 75%:

(It will be understood that in this disclosure, above and below, reference is always made to a trans isomer or a cis isomer, although in the case of tetrahydropyran compounds there are generally two trans isomers which are related to one another as image and mirror image (enantiomers) , or two cis isomers, which are also related to each other like image and mirror image (enantiomers). Furthermore, the designations trans and cis - unless otherwise stated - always refer to the stereochemistry on the central cyclohexane or tetrahydropyran ring.)

The process according to the invention is usually carried out in a homogeneous phase, the reaction of the starting compound of the formula II with hydrogen gas (introduced or dissolved into the reaction medium) taking place in the presence of the transition metal complex dissolved or suspended in the medium. However, it is also possible to bind or adsorb the transition metal complex to a conventional solid phase support and to bring the reaction mixture into contact with it.

The reaction medium is preferably a liquid solvent or mixture of solvents or a medium in the supercritical state, for example supercritical carbon dioxide (sc-CO ₂ ). The exact choice of the medium depends above all on the solubility behavior of the compound of the formula II to be reduced and of the transition metal complex used as catalyst. Suitable solvents, which can be used as the reaction medium alone or in mixtures of 2 or 3 solvents, are, for example, water; Hydrocarbons such as hexanes, petroleum ether, benzene, toluene, xylenes; chlorinated hydrocarbons such as trichlorethylene, 1,2-dichloroethane, chloroform, dichloromethane; Alcohols such as methanol, ethanol, 2-propanol, n-propanol, n-butanol, tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or 1,4-dioxane; glycol ethers such as ethylene glycol monomethyl or monoethyl ether (methyl glycol, ethyl glycol or polyethylene glycol), ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide; nitro compounds such as nitromethane or nitrobenzene; esters such as methyl acetate or ethyl acetate. Hydrocarbons, especially toluene, alcohols, especially methanol and ethanol, and chlorinated hydrocarbons, especially dichloromethane, and mixtures of hydrocarbons with alcohols, especially methanol/toluene and ethanol/toluene, are preferred.

The transition metal complex used as a catalyst in the process according to the invention is preferably a rhodium, iridium and/or ruthenium complex, rhodium complexes being particularly preferred.

The stabilizing phosphine ligands are generally phosphines having three radicals attached to the phosphorus atom, which radicals may be the same or different, or chosen such that two of the three radicals are the same and the third radical is different from the other two is. The three radicals are preferably the same. Two or three of the radicals can also be linked to one another. The radicals on the P atom are organic and/or organometallic Radicals which, together with the phosphorus atom, form a sufficiently chemically stable phosphine which can be isolated and used--if appropriate under an inert gas atmosphere and/or with the exclusion of moisture. In addition to the phosphines P(A ³¹ A ³² A ³³ ) and P(A ⁴² A ⁴³ A ⁴⁴ ) used in the complexes of the formulas III and IV given below and the other phosphine ligands of the formulas XI and XII mentioned below, there are also trialkylphosphines with three identical or different alkyl radicals such as methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl suitable stabilizing phosphine ligands. In addition to the (bidentate) bisphosphine chelating ligands of the formula XII, it is also possible to use chelating ligands, in particular bidentate chelating ligands, in which, for example, a first coordinating atom of the ligand is a phosphorus atom and a second coordinating atom of the ligand is a heteroatom other than phosphorus, for example a nitrogen atom. Examples of such P,N chelating ligands are from A. Lightfood et al., Angew. Chem. 1998, 100, No. 20, 3047-3050, and in DE 198 31 137 A1 been described. The phosphine ligand or ligands are generally selected in such a way that they stabilize the transition metal complex with regard to the hydrogenation reaction according to the invention, ie support its activity and chemical stability in the desired reaction.

A31, A32 und A33

unabhängig voneinander unsubstituierte oder substituierte Aryl-, Biphenyl-, Heteroaryl-, Heterocyclyl- oder Cycloalkylreste darstellen und in den drei Liganden P(A³¹A³²A³³) gleiche oder verschiedene Bedeutungen aufweisen, d.h. die drei Liganden P(A³¹A³²A³³) sind gleich oder verschieden;

A41

einen unsubstituierten oder substituierten Heterocyclyl- oder Heteroarylrest darstellt;

A42, A43 und A44

unabhängig voneinander unsubstituierte oder substituierte Aryl-, Biphenyl-, Heteroaryl-, Heterocyclyl- oder Cycloalkylreste darstellen, wobei einer der Reste A⁴², A⁴³ und A⁴⁴ mit A⁴¹ verbunden sein kann, z.B. über eine Einfachbindung oder eine Alkylenbrücke, so dass ein Chelatligand resultiert;

X31

einen Liganden beziehungsweise ein Anion der Formel CI, Br, I, PF₆, [PF₃(C₂F₅)₃], SbF₆, BF₄, BARF, CIO₄, CF₃SO₃, CH₃CO₂ oder CF₃CO₂ darstellt;

Y41

einen Liganden beziehungsweise ein Anion der Formel CI, Br, I, PF₆, [PF₃(C₂F₅)₃], SbF₆, BF₄, BARF, CIO₄, CF₃SO₃, CH₃CO₂ oder CF₃CO₂ darstellt; und

dien

für 1,5-Cyclooctadienyl (COD), Norbornadienyl, (Ethylen)₂ oder (Cycloocten)₂ steht.

(„BARF“ steht für Tetrakis[3,5-bis(trifluormethyl)phenylborat]-Anion,

In some embodiments of the invention, the transition metal complex is selected from a complex of formula III and formula IV [(P(A ³¹ A ³² A ³³ )) ₃ RhX ³¹ ] III [(dien)Ir(A ⁴¹ )(P(A ⁴² A ⁴³ A ⁴⁴ ))]Y ⁴¹ IV whereby

A31, A32 and A33

are independently unsubstituted or substituted aryl, biphenyl, heteroaryl, heterocyclyl or cycloalkyl radicals and have the same or different meanings in the three ligands P(A ³¹ A ³² A ³³ ), ie the three ligands P(A ³¹ A ³² A ³³ ) are the same or different;

A41

represents an unsubstituted or substituted heterocyclyl or heteroaryl radical;

A42, A43 and A44

independently represent unsubstituted or substituted aryl, biphenyl, heteroaryl, heterocyclyl or cycloalkyl radicals, where one of the radicals A ⁴² , A ⁴³ and A ⁴⁴ can be connected to A ⁴¹ , for example via a single bond or an alkylene bridge, so that a chelating ligand results;

X31

a ligand or an anion of the formula CI, Br, I, PF ₆ , [PF ₃ (C ₂ F ₅ ) ₃ ], SbF ₆ , BF ₄ , BARF, CIO ₄ , CF ₃ SO ₃ , CH ₃ CO ₂ or CF ₃ represents CO ₂ ;

Y41

a ligand or an anion of the formula CI, Br, I, PF ₆ , [PF ₃ (C ₂ F ₅ ) ₃ ], SbF ₆ , BF ₄ , BARF, CIO ₄ , CF ₃ SO ₃ , CH ₃ CO ₂ or CF ₃ represents CO ₂ ; and

serve

is 1,5-cyclooctadienyl (COD), norbornadienyl, (ethylene) ₂ or (cyclooctene) ₂ .

(“BARF” stands for tetrakis[3,5-bis(trifluoromethyl)phenylborate] anion,

The complexes of the formula III contain three identical or different phosphine ligands P(A ³¹ A ³² A ³³ ), it being preferred for the three ligands to be identical.

A ³¹ , A ³² and A ³³ can each have the same meaning or different meanings, it also being possible for two of A ³¹ , A ³² and A ³³ to have the same meaning and the third of A ³¹ , A ³² and A ³³ to have a different meaning has. A ³¹ , A ³² and A ³³ preferably have the same meaning.

A ⁴² , A ⁴³ and A ⁴⁴ can each have the same meaning or different meanings, it also being possible for two of A ⁴² , A ⁴³ and A ⁴⁴ to have the same meaning and the third of A ⁴² , A ⁴³ and A ⁴⁴ to have a different meaning has. A ⁴² , A ⁴³ and A ⁴⁴ preferably have the same meaning.

If A ³¹ , A ³² and A ³³ in formula III and A ⁴² , A ⁴³ and A ⁴⁴ in formula IV stand for an unsubstituted or substituted aryl substituent, this is preferably an unsubstituted phenyl or naphthyl radical or one or more times the same or different Alkanyl, in particular with methyl, ethyl, isopropyl, n-butyl or tert-butyl, with alkoxy, in particular with methoxy, with -NH ₂ or with -N(alkanyl) ₂ , in particular with -N(methyl) ₂ , -N(ethyl) ₂ , -N(isopropyl) ₂ or -N(ethyl)(isopropyl), substituted phenyl radical, where, in the case of substitution, monosubstitution is particularly preferred. In particular, the aryl substituent is an unsubstituted phenyl radical. Furthermore, substitution with a heterocyclyl or heteroaryl radical is preferred, in particular substitution with 4,5-dihydrooxazole or pyridine.

If A ³¹ , A ³² and A ³³ in formula III and A ⁴² , A ⁴³ and A ⁴⁴ in formula IV stand for an unsubstituted or substituted biphenyl substituent, this is preferably via the 2- or 2'-position of the biphenyl radical with the phosphorus atom of the phosphine ligand linked. The biphenyl substituent is preferably unsubstituted or--when linked via the 2-position--in the 2'-position with alkanyl, in particular with methyl, ethyl, isopropyl, n-butyl or tert-butyl, with alkoxy, in particular with methoxy -NH ₂ or substituted with -N(alkanyl) ₂ , in particular with -N(methyl) ₂ , -N(ethyl) ₂ , -N(isopropyl) ₂ or -N(ethyl)(isopropyl). in particular the biphenyl substituent is unsubstituted.

If A ³¹ , A ³² and A ³³ in formula III and A ⁴¹ , A ⁴² , A ⁴³ and A ⁴⁴ in formula IV stand for an unsubstituted or substituted heterocyclyl substituent, this is preferably a five- or six-membered heterocyclyl ring with oxygen and/or nitrogen as heteroatom(s). The heterocyclyl radical can also be partially unsaturated. More preferably, the heterocyclyl substituent is a dihydroimidazole, dihydropyrazole, dihydroisoxazole, and especially a dihydrooxazole.

If A ³¹ , A ³² and A ³³ in formula III and A ⁴¹ , A ⁴² , A ⁴³ and A ⁴⁴ in formula IV stand for an unsubstituted or substituted heteroaryl substituent, this is preferably a five- or six-membered heteroaryl ring with oxygen and/or Nitrogen as heteroatom(s). The heteroaryl radical is then particularly preferably a furanyl radical, in particular a 2-furanyl radical, or a pyridyl radical, in particular a 2-pyridyl radical.

If A ³¹ , A ³² and A ³³ in formula III and A ⁴² , A ⁴³ and A ⁴⁴ in formula IV stand for an unsubstituted or substituted cycloalkyl substituent, this is preferably a five-, six- or seven-membered cycloalkyl ring which is also substituted with alkanyl can be. It is particularly preferably a cyclohexyl radical.

A ⁴¹ is preferably an unsubstituted heteroaryl radical, particularly preferably a five- or six-membered heteroaryl ring with nitrogen as the heteroatom(s). A ⁴¹ is very particularly preferably a pyridyl radical which complexes with the transition metal via its N atom. Furthermore, A ⁴¹ is preferably a heterocyclyl radical as defined above for A ³¹ , A ³² , A ³³ , A ⁴² , A ⁴³ or A ⁴⁴ , in particular dihydrooxazole.

In a particularly preferred embodiment of the invention, A ⁴¹ is a 4,5-dihydrooxazolyl radical linked via its 2-position to the 2-position of A ⁴² representing a phenyl ring via a single bond; A ⁴³ and A ⁴⁴ are then unsubstituted or substituted aryl, in particular phenyl or ortho-tolyl, so that A ⁴¹ and P(A ⁴² A ⁴³ A ⁴⁴ ) form a bidentate chelate ligand coordinating via a P atom and via an N atom ( see. A. Lightfood et al., Angew. Chem. 1998, 110, No. 20, 3047-3050 ; DE 198 31 137 A1 ).

X ³¹ is preferably Cl or Br, especially chlorine.

Y ⁴¹ is preferably an anion of the formula PF ₆ , SbF ₆ , BF ₄ , BARF or CIO ₄ , in particular PF ₆ . diene in formula IV is preferably 1,5-cyclooctadienyl (COD) or norbornadienyl, in particular COD.

Among the complexes of formulas III and IV, the complexes of formula III are preferred. The complexes of the formula III in which A ³¹ , A ³² and A ³³ have the same meaning and are particularly preferred stand for an unsubstituted phenyl radical or monosubstituted by alkanyl and X ³¹ is chlorine. The transition metal complex of the formula III-1 is very particularly preferred: [(P(Phenyl) ₃ RhCl] III-1

In a particularly preferred embodiment of the invention, the hydrogenation according to the invention is carried out in the presence of the complex III where X ³¹ =CI, in particular the complex III-1, and an alkali metal or tetraalkylammonium bromide or iodide. This further increases conversion and trans selectivity. In addition to tetramethyl-, tetraethyl- and tetrabutylammonium bromide or iodide, particular preference is given to lithium bromide and lithium iodide, in particular lithium bromide. The amount of bromide or iodide added is generally about 0.1 to about 50 equivalents, based on the transition metal complex, preferably about 1 to about 25 equivalents, in particular about 2 to about 15 equivalents.

In another embodiment of the invention, the transition metal complex catalyzing the hydrogenation of the compound of formula II is not added to the reaction medium as such, but is formed in situ by reacting a suitable transition metal complex precursor with the stabilizing phosphine ligand or ligands. The transition metal complex precursor and the phosphine ligand(s) are usually used in a molar ratio of from about 1:1 to about 1:5, in particular from about 1:2 to about 1:3. It is preferred to use a phosphine ligand (of a type). In this process procedure according to the invention, the actual transition metal complex which catalyzes the hydrogenation is formed in situ without its precise structure being known in detail.

X61, X81 und X101

unabhängig voneinander Cl, Br oder I darstellen;

x

0, 1, 2 oder 3 ist;

Y71 und Y91

unabhängig voneinander ein Anion der Formel PF₆, [PF₃(C₂F₅)₃], SbF₆, BF₄, BARF, CIO₄, CF₃SO₃, CH₃CO₂ oder CF₃CO₂ darstellen;

dien

1,5-Cyclooctadienyl (COD), Norbornadienyl, (Ethylen)₂ oder (Cycloocten)₂ darstellt; und

allyl

Allyl oder Methallyl bedeutet;

und
der oder die Phosphinliganden aus Verbindungen der Formel XI und/oder XII ausgewählt sind: P(A¹¹¹A¹¹²A¹¹³) XI

wobei

A111, A112, A113, A121, A122, A123 und A124

unabhängig voneinander unsubstituierte oder substituierte Aryl-, Biphenyl-, Heteroaryl-, Heterocyclyl- oder Cycloalkylreste darstellen; und

G

für eine Alkylenbrücke mit 1 bis 8 Kohlenstoffatomen oder für unsubstituiertes oder substituiertes 1,2-Phenylen, 2,3-Naphthylen, 2,2'-Biphenylen oder 1,1'-Di(cyclopentadienyl)-eisen steht.

X⁶¹ und X⁸¹ sind bevorzugt Cl oder Br, insbesondere Chlor.
X¹⁰¹ ist bevorzugt Br oder I, insbesondere Brom.
x ist bevorzugt 3.
Y⁷¹ und Y⁹¹ sind bevorzugt ein Anion der Formel PF₆, SbF₆, BF₄, BARF, oder CIO₄, insbesondere BF₄ oder BARF.
dien in den Formeln V bis IX steht bevorzugt für 1,5-Cyclooctadienyl (COD) oder Norbornadienyl, insbesondere für COD.
allyl in den Formeln V bis IX steht bevorzugt für Methallyl.The transition metal complex precursors are preferably selected from a complex of the formulas V, VI, VII, VIII, IX and X: [(dien)Ru(allyl) ₂ ] V [(dien)RhX ⁶¹ ] ₂ VI [(dien) ₂ Rh]Y ⁷¹ VII [(dien)IrX ⁸¹ ] ₂ VIII [(dien) ₂ Ir]Y ⁹¹ IX RhX ¹⁰¹ ₃ .xH ₂ OX whereby

X61, X81 and X101

independently represent Cl, Br or I;

x

is 0, 1, 2 or 3;

Y71 and Y91

independently represent an anion of the formula PF ₆ , [PF ₃ (C ₂ F ₅ ) ₃ ], SbF ₆ , BF ₄ , BARF, CIO ₄ , CF ₃ SO ₃ , CH ₃ CO ₂ or CF ₃ CO ₂ ;

serve

1,5-cyclooctadienyl (COD), norbornadienyl, (ethylene) ₂ or (cyclooctene) ₂ ; and

allyl

means allyl or methallyl;

and
the phosphine ligand(s) is/are selected from compounds of the formula XI and/or XII: P(A ¹¹¹ A ¹¹² A ¹¹³ ) XI

whereby

A111, A112, A113, A121, A122, A123 and A124

independently represent unsubstituted or substituted aryl, biphenyl, heteroaryl, heterocyclyl or cycloalkyl radicals; and

G

stands for an alkylene bridge with 1 to 8 carbon atoms or for unsubstituted or substituted 1,2-phenylene, 2,3-naphthylene, 2,2'-biphenylene or 1,1'-di(cyclopentadienyl)-iron.

X ⁶¹ and X ⁸¹ are preferably Cl or Br, especially chlorine.
X ¹⁰¹ is preferably Br or I, especially bromine.
x is preferably 3.
Y ⁷¹ and Y ⁹¹ are preferably an anion of the formula PF ₆ , SbF ₆ , BF ₄ , BARF, or CIO ₄ , in particular BF ₄ or BARF.
diene in the formulas V to IX is preferably 1,5-cyclooctadienyl (COD) or norbornadienyl, in particular COD.
allyl in the formulas V to IX preferably represents methallyl.

With regard to the phosphine ligands of the formula XI, A ¹¹¹ , A ¹¹² and A ¹¹³ can each have the same meaning or different meanings, it also being possible for two of A ¹¹¹ , A ¹¹² and A ¹¹³ to have the same meaning and the third of A ¹¹¹ , A ¹¹² and A ¹¹³ has a different meaning. A ¹¹¹ , A ¹¹² and A ¹¹³ preferably have the same meaning.

With regard to the phosphine ligands of the formula XII, A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ can each have the same meaning or different meanings, with two or three of A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ also having the same meaning and the other two or the fourth of A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ have/has a different meaning. A ¹²¹ and A ¹²² and A ¹²³ and A ¹²⁴ preferably have the same meaning. More preferably, all four of A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ have the same meaning.

If A ¹¹¹ , A ¹¹² and A ¹¹³ in formula XI and A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ in formula XII stand for an unsubstituted or substituted aryl substituent, this is preferably an unsubstituted phenyl or naphthyl radical or a monovalent or polyvalent radical or differently with alkanyl, in particular with methyl, ethyl, isopropyl, n-butyl or tert-butyl, with alkoxy, in particular with methoxy, with -NH ₂ or with -N(alkanyl) ₂ , in particular with -N(methyl ) ₂ , -N(ethyl) ₂ , -N(isopropyl) ₂ or -N(ethyl)(isopropyl), substituted phenyl radical, with monosubstitution being particularly preferred in the case of substitution. In particular, the aryl substituent is unsubstituted phenyl or methyl-substituted phenyl (o-, m- and/or p-tolyl).

If A ¹¹¹ , A ¹¹² and A ¹¹³ in formula XI and A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ in formula XII stand for an unsubstituted or substituted biphenyl substituent, this is preferably via the 2- or 2'-position of the biphenyl radical linked to the phosphorus atom of the phosphine ligand. The biphenyl substituent is preferably unsubstituted or--when linked via the 2-position--in the 2'-position with alkanyl, in particular with methyl, ethyl, isopropyl, n-butyl or tert-butyl, with alkoxy, in particular with methoxy -NH ₂ or substituted with -N(alkanyl) ₂ , in particular with -N(methyl) ₂ , -N(ethyl) ₂ , -N(isopropyl) ₂ or -N(ethyl)(isopropyl). In particular, the biphenyl substituent is unsubstituted.

If A ¹¹¹ , A ¹¹² and A ¹¹³ in formula XI and A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ in formula XII stand for an unsubstituted or substituted heteroaryl substituent, this is preferably a five- or six-membered heteroaryl ring with oxygen and/or Nitrogen as heteroatom(s). The heteroaryl radical is then particularly preferably a furanyl radical, in particular a 2-furanyl radical, or a pyridyl radical, in particular a 2-pyridyl radical.

If A ¹¹¹ , A ¹¹² and A ¹¹³ in formula XI and A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ in formula XII stand for an unsubstituted or substituted heterocyclyl substituent, this is preferably a five- or six-membered heterocyclyl ring with oxygen and/or nitrogen as heteroatom(s). The heterocyclyl radical can also be partially unsaturated. More preferably, the heterocyclyl substituent is a dihydroimidazole, dihydropyrazole, dihydroisoxazole, and especially a dihydrooxazole.

If A ¹¹¹ , A ¹¹² and A ¹¹³ in formula XI and A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ in formula XII stand for an unsubstituted or substituted cycloalkyl substituent, this is preferably a five-, six- or seven-membered cycloalkyl ring which may also be substituted with alkanyl. It is particularly preferably a cyclohexyl radical.

If G in formula XII is an alkylene bridge, this preferably has 1, 2, 3, 4, 5 or 6 carbon atoms. The alkylene bridge is particularly preferably -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ - or -(CH ₂ ) ₄ -.

If G in formula XII is a 1,2-phenylene radical or a 2,3-naphthylene radical, these are mono- or disubstituted by alkanyl or alkoxy, or preferably unsubstituted. G is particularly preferably an unsubstituted 1,2-phenylene radical.

If G is a 2,2′-biphenylene radical, this is unsubstituted or identical or different one or more times with alkanyl, in particular with methyl, ethyl, isopropyl, n-butyl or tert-butyl, with alkoxy, in particular with methoxy , with -NH ₂ or with -N(alkanyl) ₂ , in particular with -N(methyl) ₂ , -N(ethyl) ₂ , -N(isopropyl) ₂ or -N(ethyl)(isopropyl), substituted. The substitution sites are the 5-, 6-, 5'- and/or 6'-position. The biphenyl radical is particularly preferably unsubstituted.

In one embodiment of the invention, G is 1,1'-ferrocenyl (1,1'-di(cyclopentadienyl)iron).

The phosphine ligands added to the transition metal complex precursor are preferably phosphine ligands of formula XI. It is further preferred that A ¹¹¹ , A ¹¹² and A ¹¹³ are the same and represent an aryl substituent, which is particularly preferably an unsubstituted phenyl radical or a methyl-substituted phenyl radical (o-, m- and/or p-tolyl).

In a preferred embodiment of the invention, the transition metal complex precursor is a complex of formula VI-1: [(COD)RhCl] ₂ VI-1 and the phosphine ligand(s) is triphenylphosphine or tri(ortho-tolyl)phosphine.

When a transition metal complex precursor of formula X is employed in the process of the present invention, it may be advantageous to further add a base such as triethylamine or the like to the reaction mixture in an amount sufficient to scavenge the hydrohalic acid formed during the reaction.

If at least one of the ligands of the transition metal complex or the transition metal complex precursor or one of the added phosphine ligands is selected in such a way that the species catalyzing the hydrogenation according to the invention induces chiral information, e.g. because it is itself chiral or has C ₂ symmetry, then in the case of the 2-position a chiral center having racemic dihydropyrans of the formula II not only possible to carry out the hydrogenation trans-selectively, but also diastereoselectively with preferred formation of only one of the two possible trans-isomers on the basis of a kinetic racemate resolution. If the dihydropyrans of the formula II to be hydrogenated already consist of a pure enantiomer (relative to the 2-position), a second chiral center with a uniform chirality in the 5-position is obtained even without using a chiral ligand in trans-hydrogenation, the use of a chiral ligands of the appropriate configuration can enhance chiral induction.

The process according to the invention is usually carried out using hydrogen (H ₂ ) introduced into the reaction medium or dissolved in the medium. The hydrogen pressure is not critical per se and is chosen depending, inter alia, on the reaction rate. The hydrogenation takes place at a hydrogen pressure of about 1 bar to about 200 bar, preferably at about 3-100 bar, in particular at about 6 to about 60 bar hydrogen pressure.

The hydrogenation takes place in a pressure-resistant container and preferably with the exclusion of oxygen.

The choice of reaction temperature is not critical in itself, provided the hydrogenation proceeds quickly enough without undesired decomposition of the reactants and reagents. In general, the reaction temperature is in a range from about 0°C to about 200°C, preferably between about 10°C and about 150°C, more preferably between about 60°C and about 130°C and especially between about 80°C and 100°C.

The amount of catalyst used depends on the need to achieve a sufficiently high reaction rate and the highest possible conversion, on the other hand on economic requirements to keep the amount of catalyst as low as possible, and on the catalytic activity duration of the complex used or on the rapidity with which the catalyst is deactivated. The molar ratio between the transition metal complex or the transition metal complex precursor used as catalyst and the substrate, ie the compound of the formula II, is usually between 1:50,000 and 1:50, ie the transition metal complex or transition metal complex precursor is present in approx. 0.02 mol % to approx 2 mole %, based on the substrate, is used. More preferably, the amount of catalyst is about 0.2 mole percent to about 1.5 mole percent, especially about 0.8 mole percent to about 1.2 mole percent. The transition metal complex or the transition metal complex precursor is usually added to the reaction mixture in a single portion, but it is also possible to add it in several portions over the course of the reaction.

The reaction time is essentially determined by the reaction rate and is usually between about 1 minute and about 14 days. It is preferably chosen to be between about 30 minutes and about 48 hours, particularly preferably between about 2 hours and about 24 hours.

The process according to the invention is particularly suitable for the transselective hydrogenation of compounds of the formula II in which W is oxygen (-O-), i.e. for the reduction of dihydropyran derivatives of the formula II to tetrahydropyrans of the formula I. The process according to the invention is particularly preferred for the preparation of tetrahydropyrans of the formula IA from dihydropyrans of the formula IIA.

If W is CH ₂ , it is also preferred to carry out the process according to the invention using a cyclohexene derivative of the formula IIB.

Furthermore, it is preferred that the compounds of the formula II have at least one further ring in addition to the central cyclohexene or dihydropyran ring. It is particularly preferred that in formula II the sum of f, g, h, i and j and correspondingly in formula I the sum of a, b, c, d and e is less than or equal to 3. These sums are very particularly preferably either 1 or 2, i.e. the compounds of the formulas I and II have one or two further rings or ring systems in addition to the central cyclohexene or dihydropyran ring.

In a preferred embodiment of the invention, the radicals, rings and indices in formulas I and II are selected such that: a, d, f and i are 0; b and g are 0 or 1; c and h are 0 or 1; e and j 1 are; ^A12 and ^A22 an unsubstituted 1,4-cyclohexylene radical, provided that b or g is 1; ^A13 and ^A13 an unsubstituted 1,4-cyclohexylene radical or an unsubstituted 1,4-phenylene radical or mono- or polysubstituted by halogen, provided that c or h is 1; ^A15 and ^A25 a 1,4-phenylene radical which is unsubstituted or mono- or polysubstituted by halogen; ^R11 and ^R21 represents an alkanyl radical with 1 to 8 carbon atoms; ^Y11 and ^Y21 an unsubstituted or mono- or polysubstituted alkanyl or alkoxy radical having 1 to 8 carbon atoms, an unsubstituted or substituted aralkyl or aralkyl-O radical having 7 to 12 carbon atoms, F, CI, Br or CN; Z ¹² a single bond, -CH ₂ CH ₂ -, -CO-O- or -O-CO-; Z ¹³ and Z ²³ represent a single bond or -CO-O-; Z ¹⁴ and Z ²⁴ a single bond, -CF ₂ O- or -CO-O-, provided that c or h is 1; and Z ²² a single bond, -CH ₂ CH ₂ -, -CH=CH-, -CO-O- or -O-CO-.

It is particularly preferred that Z ²² represents a CH═CH group which, in addition to the endocyclic CC double bond of the central cyclohexene or dihydropyran ring, is also hydrogenated when the process according to the invention is carried out. (The same also applies to other aliphatic or cycloaliphatic CC double bonds present in the compound of the formula II.) Z ²² is very particularly preferably a CH=CH group in compounds of the formula IIA, in particular where W=—O—.

Preferred compounds of the formula IIA where W=-O- to be hydrogenated by the process according to the invention are the following compounds:

n is 1, 2, 3, 4, 5, 6, 7 or 8, in particular 1, 2, 3, 4 or 5, and in the compounds of the formulas IIAh, IIAi and IIAj also zero. Y ²¹ has the same meaning as for formula IIA above and is preferably F, CI, Br, CF ₃ , OCH ₃ , OCF ₃ or aralkyl-O-, particularly preferably F. The substituents L ²¹ and L ²² are each independently H, CI, Br or F, preferably at least one F, in particular both F.

Preferred compounds of the formula IIB where W = -CH ₂ - to be hydrogenated by the process according to the invention are the following compounds:

n is 1, 2, 3, 4, 5, 6, 7 or 8, in particular 1, 2, 3, 4 or 5. Y ²¹ has the same meaning as for formula IIB above and is preferably F, CI, Br, CF ₃ , OCH ₃ , OCF ₃ or aralkyl-O-, particularly preferably F or OCH ₃ . The substituents L ²¹ , L ²² , L ²³ and L ²⁴ independently represent H, CI, Br or F, it being preferred that two of L ²¹ , L ²² , L ²³ and L ²⁴ are F and the other two are H . L ²¹ and L ²² F and L ²³ and L ²⁴ H or L ²¹ and L ²³ F and L ²² and L ²⁴ H are particularly preferred.

Further exemplary compounds of the formula II which can be used in the process according to the invention can be found in the attached examples.

In a preferred embodiment of the invention, after the hydrogenation of the compound of the formula II, a further process step is the crystallization of the trans isomer of the formula I from a suitable solvent, for example an alcoholic solvent such as methanol or ethanol.

The cyclohexene compounds of the formula II are known from the literature. They can also be prepared by methods known per se, as described in the literature (e.g. in standard works on synthetic organic chemistry such as Houben-Weyl, Methods of Organic Chemistry, Georg-Thieme-Verlag, Stuttgart), under reaction conditions which are known and suitable for the reactions mentioned. However, it is also possible to make use of variants that are known per se and are not mentioned in more detail here. A suitable general procedure exemplified for some compounds in the EP 0 415 090 A1 describes the addition of a suitably substituted alkyl, cycloalkyl or aryl Grignard compound to the carbonyl function of a suitably substituted cyclohexanone derivative with subsequent elimination of the tertiary alcohol function formed in the Grignard reaction with formation of the endocyclic CC double bond.

The dihydropyran derivatives of the formula II are also known from the literature or can be prepared by methods known per se, as described in the literature (e.g. in standard works on synthetic organic chemistry such as Houben-Weyl, Methods of Organic Chemistry, Georg-Thieme-Verlag, Stuttgart ), under reaction conditions which are known and suitable for the reactions mentioned. However, it is also possible to make use of variants that are known per se and are not mentioned in more detail here. In a particularly elegant manner, the dihydropyran derivatives of the formula II in which Z ²² does not represent a CC double bond are linked by a ring-closing cross-metathesis ( DE 10324312.7 ) and the dihydropyran derivatives of the formula II, in which Z ²² represents a CC double bond, by an enyne metathesis and optionally a further cross metathesis ( DE 10324348.8 ), each in the presence of a suitable metal-carbene complex (for example the Grubbs I or Grubbs II catalyst or related catalysts; see inter alia WO 96/04289 ; WO 97/06185 ; TM Trnka et al., Acc. Chem. Res. 2001, 34, 18; SK Armstrong, J. Chem. Soc., Perkin Trans. I, 1998, 371; J. Renaud et al., Angew. Chem. 2000, 112, 3231 ) accessible. These two processes are outlined in Scheme 1a and Scheme 1b for compounds of the formula IIA, and the procedure can also be readily applied to compounds of the formula IIB:

To protect any reactive functional groups or substituents present in the molecule from undesired reactions in the reduction according to the invention and/or preceding or subsequent reaction and/or work-up steps, protective groups can be used which can be split off again after the reaction has taken place. Methods for using appropriate protecting groups are known to those skilled in the art and are described, for example, in T.W. Greene, P.G.M. Wuts: Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons (1999).

The reagents used, in particular the transition metal complexes and transition metal complex precursors, are known from the literature and are mostly commercially available, for example from Sigma-Aldrich Chemicals (Steinheim, Germany) or Strem Chemicals (Newburyport, MA, USA). Alternatively, they can be prepared by methods known per se, as described in the literature (e.g. in standard works such as "Inorganic Synthesis" (McGraw-Hill or Wiley, New York, 1939ff.)), under reaction conditions for the said reactions are known and suitable. However, it is also possible to make use of variants that are known per se and are not mentioned in more detail here.

A further subject [partly not according to the claims] of the present invention is a composition comprising
a compound of formula IIA or IIB as defined above
and
one as defined above stabilized with one or more identical or different phosphine ligands
transition metal complex,
and the use of this composition to prepare compounds of formula IA or IB.

In the context of the present invention, the term "alkyl" - unless otherwise defined elsewhere in this specification or in the claims - means a straight-chain or branched aliphatic hydrocarbon radical having 1 to 15 (i.e. 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms; this radical is unsubstituted or substituted once or several times, identically or differently, by fluorine, chlorine, bromine, iodine or cyano.

If this alkyl radical is a saturated radical, it is also referred to as "alkanyl". Furthermore, the term “alkyl”—unless defined differently elsewhere in the description or in the claims in individual cases—also includes unsubstituted or correspondingly identical or different F, CI, Br, I and/or -CN one or more times substituted hydrocarbon radicals in which one or more CH ₂ groups are replaced by -O- ("alkoxy", "oxaalkyl"), -S-("thioalkyl"), -CH=CH- ("alkenyl"), -C≡ C- ("alkynyl"), -CO-O-, -O-CO- or -O-CO-O- can be replaced, that heteroatoms (O, S) are not linked directly to each other. (In the compounds of formula I, "alkyl" does not also include alkenyl radicals.) Preferably, alkyl is a straight-chain or branched, unsubstituted or substituted alkanyl, alkenyl or alkoxy radical having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. If alkyl is an alkanyl radical, this is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl ; _CF3 , _CHF2 , _CH2 F; _{CF2 CF3} . The alkanyl radical is particularly preferably straight-chain and unsubstituted or substituted by F.

Since one or more CH ₂ groups in an alkyl radical can be replaced by -O-, the term "alkyl" also includes "alkoxy" or "oxaalkyl" radicals. By alkoxy is meant an O-alkyl radical in which the oxygen atom is directly connected to the group or ring substituted by the alkoxy radical and alkyl is as defined above; alkyl is then preferably alkanyl or--if the radical is not contained in a compound of the formula I--alkenyl. Preferred alkoxy radicals are methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy and octoxy, any of these radicals also being substituted, preferably with one or more fluorine atoms. Alkoxy -OCH ₃ , -OC ₂ H ₅ , -OnC ₃ H ₇ , _{-OnC 4} H 9 , -OtC ₄ H ₉ , -OCF ₃ , -OCHF ₂ , -OCH ₂ F or -OCHFCHF ₂ is particularly preferred. In the context of the present invention, the term "oxaalkyl" means alkyl radicals in which at least one non-terminal CH ₂ group is replaced by -O- such that there are no adjacent heteroatoms (O,S). Preferably, oxaalkyl includes straight chain radicals of the formula C _e H _2e+1 -O-(CH ₂ ) _f - where e and f are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 ; e is particularly preferably an integer from 1 to 6 and f is 1 or 2.

If one or more CH ₂ groups are replaced by sulfur in an alkyl radical as defined above, a “thioalkyl” radical is present. Preferably, "thioalkyl" includes a straight-chain radical of the formula C _e H _2e+1 -S-(CH ₂ ) _f -, where e is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 and f is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; e is particularly preferably an integer from 1 to 6 and f is 0, 1 or 2. The thioalkyl radical can also be substituted by F, Cl, Br, I and/or -CN and is preferably unsubstituted.

In the context of the present invention the term "alkenyl" means an alkyl radical as defined above in which one or more -CH=CH- groups are present. If two -CH=CH groups are present in the radical, this can also be referred to as "alkadienyl". An alkenyl radical can contain from 2 to 15 (ie, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms and is branched tig or preferably straight chain. The radical is unsubstituted or substituted one or more times, identically or differently, with F, Cl, Br, I and/or CN. Furthermore, one or more CH ₂ groups can each independently be replaced by -O-, -S-, -C≡C-, -CO-O-, -OC-O-, -O-CO-O- so that heteroatoms (O, S) are not directly connected to each other. If the CH=CH group has a moiety other than hydrogen on both carbon atoms, such as when it is a non-terminal group, the CH=CH group can exist in two configurations, namely the E isomer and the Z isomer. In general, the E-isomer (trans) is preferred. The alkenyl radical preferably contains 2, 3, 4, 5, 6 or 7 carbon atoms and is vinyl, 1E-propenyl, 1E-butenyl, 1E-pentenyl, 1E-hexenyl, 1E-heptenyl, 2-propenyl, 2E-butenyl, 2E- pentenyl, 2E-hexenyl, 2E-heptenyl, 3-butenyl, 3E-pentenyl, 3E-hexenyl, 3E-heptenyl, 4-pentenyl, 4Z-hexenyl, 4E-hexenyl, 4Z-heptenyl, 5-hexenyl and 6-heptenyl. Particularly preferred alkenyl radicals are vinyl, 1E-propenyl and 3E-butenyl.

If one or more CH ₂ groups in an alkyl radical are replaced by -C≡C, an alkynyl radical is present. When a CH ₂ group is replaced by -CO, an alkyl keto group is present. It is also possible to replace one or more CH ₂ groups with -CO-O- or -O-CO-. The following of these radicals are preferred: acetyloxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, acetyloxymethyl, propionyloxymethyl, butyryloxymethyl, pentanoyloxymethyl, 2-acetyloxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 2-acetyloxypropyl, 3-propionyloxypropyl, 4-acetyloxybutyl, Methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, 2-(methoxycarbonyl)ethyl, 2-(ethoxycarbonyl)ethyl, 2-(propoxycarbonyl)ethyl, 3-(methoxycarbonyl)propyl, 3- (ethoxy-carbonyl)-propyl or 4-(methoxycarbonyl)-butyl.

In the context of the present invention, "alkylene" or "alkylene bridge" - unless the terms are defined differently elsewhere in this description or in the claims - for a divalent aliphatic hydrocarbon radical with 1, 2, 3, 4, 5, 6, 7 , 8 carbon atoms in the chain, which can optionally also be substituted once or several times with halogen, CN, carboxy, nitro, alkanyl, alkoxy, -NH ₂ or with -N(alkanyl) ₂ , the multiple substitution with the same or with different Substituents can be done. “Alkylene” or “alkylene bridge” preferably represents a straight-chain, unsubstituted aliphatic radical or mono- or disubstituted by methyl, saturated aliphatic radical having 1, 2, 3, 4, 5, 6 carbon atoms, in particular —CH ₂ CH ₂ —, —CH ₂ CH ₂ CH ₂ -, -(CH ₂ ) ₄ - and -CH ₂ C(CH ₃ ) ₂ CH ₂ -.

In the context of the present invention, the term "aryl" - unless it is defined differently elsewhere in the description or in the claims in individual cases - means an aromatic hydrocarbon having 6 to 14 carbon atoms, which may be substituted with halogen, nitro, alkanyl, alkoxy, -NH ₂ or -N(alkanyl) ₂ is mono- or polysubstituted, identically or differently, in particular a phenyl or naphthyl radical.

In the context of the present invention, the term "cycloalkyl" means a cyclic aliphatic radical having 3 to 16 carbon atoms, which is saturated or partially unsaturated and optionally substituted with halogen, carboxy, nitro, alkanyl, alkoxy, -NH ₂ or with -N(alkanyl) ₂ is substituted one or more times, identically or differently. It is preferably unsubstituted and has 5, 6 or 7 carbon atoms. In particular, cycloalkyl represents a cyclohexyl radical.

For the purposes of the present invention, a “heteroaryl radical” is understood as meaning a cyclic, (hetero)aromatic organic radical having 5 to 18 ring atoms which, in addition to carbon atoms, contains one or more identical or different heteroatoms in its cycle, these heteroatoms being composed of nitrogen, oxygen and sulfur are selected. The heterocycle has at least one ring and may also have two, three or more rings, optionally fused together, with at least one of the plurality of rings having at least one heteroatom. In the same way as the aryl radical defined above, the heteroaryl radical can be unsubstituted or substituted once or several times, identically or differently, by halogen, nitro, alkanyl, alkoxy, -NH ₂ or by -N(alkanyl) ₂ . The heteroaryl radical can be attached through any of its ring atoms. The heteroaryl radical is preferably selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyranyl, benzofuranyl, benzothienyl. Heteroaryl is particularly preferred, pyridinyl or furanyl.

For the purposes of the present invention, a “heterocyclyl radical” is understood to mean a cyclic organic radical having 5 to 18 ring atoms, which has at least one saturated (endocyclic) bond between two ring atoms in its cycle, is non-aromatic and has one or more identical or contains various heteroatoms selected from nitrogen, oxygen and sulfur. The heterocycle has at least one ring and may also have two, three or more rings, optionally fused together, with at least one of the plurality of rings having at least one heteroatom. In the same way as the aryl radical defined above, the heterocyclyl radical can be unsubstituted or substituted once or several times, identically or differently, by halogen, nitro, alkanyl, alkoxy, -NH ₂ or by -N(alkanyl) ₂ . The heteroaryl radical can be attached through any of its ring atoms. Preferably the heteroaryl radical is selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, tetrahydrofuran, dioxane, dihydropyrazole, dihydroimidazole, dihydrooxazole, tetrahydrooxazole, dihydroisoxazole and tetrahydroisoxazole. The heterocyclyl radical is particularly preferably dihydrooxazole.

In the context of the present invention, the term "aralkyl" represents an aryl-alkyl radical, ie a radical in which an aryl substituent is linked via an alkyl bridge to an atom, chain, other radical or functional group. The alkyl bridge is preferably a saturated divalent hydrocarbon radical, in particular methylene (-CH ₂ -) and ethylene (-CH ₂ -CH ₂ -). Preferred examples of an aralkyl group are benzyl and phenethyl. An “aralkyl-O- radical” for the purposes of the present invention is an aralkyl radical which is linked to another atom, chain, radical or functional group via an oxygen atom bonded to the alkyl bridge. Preferred examples of an aralkyl-O radical are O-benzyl and O-CH ₂ CH ₂ phenyl.

In the context of this invention, halogen means fluorine, chlorine, bromine or iodine.

The following examples are intended to further illustrate the present invention without limiting its scope.

examples

The starting compounds used in the examples were prepared by methods known from the literature.

The transition metal complexes and transition metal catalysts used were purchased from Strem Chemicals and Merck KGaA (Darmstadt, Germany) and used without further purification.

The solvents were of analytical grade and degassed prior to use.

The reactions took place with the exclusion of oxygen.

The hydrogenation conversion was determined by gas chromatography (GC) (Varian Chrompack CP-3800, standard conditions). The composition of the product mixture and the cis/trans selectivity of the reaction were also determined using gas chromatography.

Example 1 [not according to the claims]

37 mg (0.04 mmol) of tris(triphenylphosphine)rhodium(I) chloride were added to 0.73 g (2.0 mmol) of the olefin 1 in a pressure autoclave. After the addition of 6 ml of ethanol and 2 ml of toluene, the autoclave was closed and degassed by forcing in nitrogen at 5 bar three times and then letting it down. 6 bar of hydrogen were injected and the mixture was heated to 100.degree. After 21 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 73% converted. The product 2 was obtained with a trans content of 76%.

Comparative example 1

The hydrogenation of the olefin 1 was repeated under conditions comparable to those in Example 1, with the exception that 5% palladium on activated carbon was used instead of the tris(triphenylphosphine)rhodium(I) chloride. With a conversion of 100% in THF at 1 bar hydrogen pressure and room temperature, the product 2 with a trans content of 38% was obtained.

example 2

56 mg (0.06 mmol) of tris(triphenylphosphine)rhodium(I) chloride were added to 1.94 g (6.0 mmol) of the diene 3 in a pressure autoclave. After the addition of 36 ml of methanol and 12 ml of toluene, the autoclave was closed and degassed by forcing in 10 bar of nitrogen three times and then depressurizing. 60 bar of hydrogen were injected and the mixture was heated to 80.degree. After 20 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 99% converted. The product 4 was obtained with a trans content of 73%.

Comparative example 2

The hydrogenation of the olefin 5 was carried out under comparable conditions as in Example 2, substituting 5% palladium on activated carbon for the tris(triphenylphosphine)rhodium(I) chloride. With a conversion of 100% in heptane at 1 bar hydrogen pressure and room temperature, the product 6 with a trans content of 27% was obtained.

Example 3

In a pressure autoclave, 7141 mg (0.15 mmol) of tris(triphenylphosphine)rhodium(I) chloride were added to 6.20 g (16.0 mmol) of the diene. After the addition of 50 ml of methanol and 15 ml of toluene, the autoclave was closed and degassed by forcing in 10 bar of nitrogen three times and then depressurizing. 60 bar of hydrogen were injected and the mixture was heated to 80.degree. After 20 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 96% converted. The product 8 was obtained with a trans content of 74%.

example 4

In a pressure autoclave, 9 mg (0.01 mmol) of tris(triphenylphosphine)rhodium(I) chloride and 12 mg of lithium bromide were added to 0.10 g (0.3 mmol) of the olefin. After the addition of 6 ml of ethanol, the autoclave was closed and degassed by forcing in 5 bar of nitrogen three times and then depressurizing. 7 bar of hydrogen were injected and the mixture was heated to 100.degree. After 15 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 88% converted. The product 10 was obtained with a trans content of 77%.

When the same reaction was carried out under identical conditions, but without the addition of lithium bromide, a conversion of 80% was achieved and the product 10 with a trans content of 73% was obtained.

Example 5

In a pressure autoclave, 1.8 g (1.95 mmol) of tris(triphenylphosphine) rhodium(I) chloride were added to 14.7 g (38.3 mmol) of the olefin 11 . After the addition of 180 ml of ethanol and 60 ml of toluene, the autoclave was closed and degassed by forcing in 10 bar of nitrogen three times and then letting down the pressure. 10 bar of hydrogen were injected and the mixture was heated to 100.degree. After 45 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 100% converted. The product 12 was obtained with a trans content of 77%.

Example 6

In a pressure autoclave, 0.75 g (0.81 mmol) of tris(triphenylphosphine) rhodium(I) chloride were added to 11.1 g (40.6 mmol) of the olefin 13 . After the addition of 60 ml of ethyl methyl ketone and 60 ml of toluene, the autoclave was closed and degassed by forcing in 10 bar of nitrogen three times and then letting the pressure down. 11 bar of hydrogen were injected and the mixture was heated to 100.degree. After 17 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 100% converted. The product 14 was obtained with a trans content of 61%.

Example 7

4.50 g (4.86 mmol) of tris(triphenylphosphine)rhodium(I) chloride were added to 150 g (0.48 mol) of the diene 15 in a pressure autoclave. After the addition of 1200 l of ethanol and 400 ml of toluene, the autoclave was closed and degassed by forcing in 50 bar of nitrogen three times and then depressurizing. 8 bar of hydrogen were injected and the mixture was heated to 80-95.degree. After 34 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 100% converted. The product 16 was obtained with a trans content of 79%.

example 8

In a pressure autoclave, 0.40 g (0.43 mmol) of tris(triphenylphosphine)rhodium(I) chloride were added to 12.5 g (40.6 mmol) of the olefin 17 . After the addition of 100 ml of ethanol and 30 ml of toluene, the autoclave was closed and degassed by forcing in nitrogen at 50 bar three times and then letting it down. 16 bar of hydrogen were injected and the mixture was heated to 80.degree. After 17 hours the reaction vessel was allowed to cool and the contents analyzed by gas chromatography. The starting material was 100% converted. The product 18 was obtained with a trans content of 79%.

example 9

The reaction from Example 2 was repeated, varying the experimental conditions and using different transition metal complexes or transition metal complex precursors. 1 mol % of the respective complex and optionally about 2 or about 3 equivalents, based on the complex, of a stabilizing phosphine were used. The reaction time was 15 hours. Further information on the test conditions and the results are given in Table 1. Table 1 metal complex precursor phosphine additive Amount of diene [mmol] Equivalent phosphine solvent Temperature [°C] H ₂ pressure [bar] Total sales [%] % trans [(COD)Ru(methallyl) ₂ ] [not according to the claims] P(o-tolyl) ₃ 1 2 _{CH2Cl2 _} 50 6 50 63 [(COD)(py)Ir(PCy ₃ )] PF ₆ *[not according to the claims] - 1 - _{CH2Cl2 _} 50 6 54 58 [(PPh ₃ ) ₃ RhCl] - 6 - MeOH/ toluene = 3:1 80 60 95 73 [(PPh ₃ ) ₃ RhCl] 2.8 - MeOH/ toluene = 3:1 100 5 91 74 [(PPh ₃ ) ₃ RhCl] - 1 - ethanol 100 5 82 73 [(COD)RhCl] ₂ PPh ₃ 1 3 MeOH/ toluene = 3:1 100 5 97 74 [(COD)RhCl] ₂ P(o-tolyl) ₃ 1 3 MeOH/ toluene = 3:1 100 5 30 53 [(COD) _RhBF4 ] P(o-tolyl) ₃ 1 3 ethanol 100 5 46 51
*: py = pyridine; Cy = cyclohexyl

Example 10

56 g (0,233 mol) des Olefins wurden in 450 ml Methanol und 120 ml Toluol mit 2,2 g Tris(triphenylphosphin)-rhodium-I-chlorid bei 8 bar Wasserstoffdruck und 80 °C 4h hydriert. Nach dem Abkühlen wurde das Reaktionsgemisch im Vakuum eingedampft und über Kieselgel mit Toluol/Heptan (3:7) filtriert. Der nach dem Verdampfen des Lösungsmittels verbleibende Filtratrückstand wurde bei 0,8 mbar destilliert und die zwischen 148 °C und 167 °C übergehende Fraktion über Kieselgel chromatographiert (Eluent: Toluol/Heptan (5/95 bis 2/8)). Nach dem Eindampfen werden 33,0 g des hydrierten Produktes 20 mit 85 % trans-Anteil als Öl erhalten.

56 g (0.233 mol) of the olefin were hydrogenated in 450 ml of methanol and 120 ml of toluene with 2.2 g of tris(triphenylphosphine)rhodium-I chloride at a hydrogen pressure of 8 bar and 80° C. for 4 hours. After cooling, the reaction mixture was evaporated in vacuo and filtered through silica gel using toluene/heptane (3:7). The filtrate residue remaining after evaporation of the solvent was distilled at 0.8 mbar and the fraction passing between 148° C. and 167° C. was chromatographed on silica gel (mobile phase: toluene/heptane (5/95 to 2/8)). After evaporation, 33.0 g of the hydrogenated product 20 with 85% trans content are obtained as an oil.

Analogously, trans-2-(4-chlorophenyl)-5-propyltetrahydropyran is prepared from the corresponding olefin with a trans content of 78% and trans 2-(4-chlorophenyl)-5-(trans-4-propylcyclohexyl) -tetrahydropyrans with a trans content of 86%.

Example 11

10 g (34 mmol) des Olefins wurden in 60 ml Methanol und 18 ml Toluol mit 314 mg (339 µmol) Tris(triphenylphosphin)-rhodium-I-chlorid 17,5 h bei 8 bar und 80 °C bis zur Aufnahme der theoretischen Wasserstoffmenge hydriert. Nach dem Abkühlen des Reaktionsgemisches und Verdampfen des Lösungsmittels wurde der Rückstand über Kieselgel mit Toluol/Heptan (3:7) filtriert. Nach dem Eindampfen des Filtrats verbleibt ein Rückstand von 8,1 g, in dem die trans- und cis-Isomeren in einem Verhältnis von 71:29 vorhanden sind.

10 g (34 mmol) of the olefin were dissolved in 60 ml of methanol and 18 ml of toluene with 314 mg (339 μmol) of tris(triphenylphosphine)rhodium-I chloride for 17.5 h at 8 bar and 80° C. until the theoretical Amount of hydrogen hydrogenated. After cooling the reaction mixture and evaporating the solvent, the residue was filtered through silica gel with toluene/heptane (3:7). After evaporation of the filtrate there remains a residue of 8.1 g, in which the trans and cis isomers are present in a ratio of 71:29.

The trans-2-(4-bromophenyl)-5-ethyltetrahydropyran is prepared analogously from the corresponding olefin with a trans content of 76%.

Claims (7)

A process for preparing a compound of formula IA or IB

wherein a, d, f and i are 0; b and g are 0 or 1; c and h are 0 or 1; e and j 1 are; ^A11 , ^A14 , ^X21 and ^A24 a 1,4-cyclohexylene radical or a 1,4-phenylene radical mono- or polysubstituted by halogen, ^A12 and ^A22 an unsubstituted 1,4-cyclohexylene radical, provided that b or g is 1; ^A13 and ^A23 an unsubstituted 1,4-cyclohexylene radical or an unsubstituted 1,4-phenylene radical or mono- or polysubstituted by halogen, provided that c or h is 1; ^A15 and ^A25 a 1,4-phenylene radical which is unsubstituted or mono- or polysubstituted by halogen; ^R11 Hydrogen, an unsubstituted or singly or multiply identically or differently substituted alkyl radical having up to 8 carbon atoms, in which radicals one or more CH ₂ groups can also be replaced independently by -O- or -O-CO- such that heteroatoms (-O-) are not linked directly to each other, where R ¹¹ is not hydrogen when both a and b are zero and Z ¹² is a single bond; ^Y11 and ^Y21 an unsubstituted or mono- or polysubstituted F alkyl or alkoxy radical having 1 to 8 carbon atoms, an unsubstituted or substituted aralkyl or aralkyl-O radical having 7 to 12 carbon atoms, F, Cl, Br or CN; Z ¹¹ , Z ¹² , Z ¹⁵ , Z ²¹ , Z ²² , and Z ²⁵ a single bond, Z ¹³ and Z ²³ represent a single bond or -CO-O-; Z ¹⁴ and Z ²⁴ a single bond or -CF ₂ O-, provided that c or h is 1; and W -O- means; characterized in that a compound of formula IIA or a compound of formula IIB

where R ²¹ is hydrogen, an unsubstituted or mono- or polysubstituted alkyl radical having 1 to 8 carbon atoms, where in these radicals one or more CH ₂ groups are independently represented by -CH=CH-, -O- or - O-CO- can be replaced that heteroatoms (-O-) are not linked directly to one another, where R ²¹ is not hydrogen if f and g are both zero and Z ²² is a single bond, and the other parameters as under formula IA and IB are defined. procedure according to claim 1 , characterized in that the rhodium complex is a complex of the formula: [(P(A ³¹ A ³² A ³³ )) ₃ RhX ³¹ ] III where A ³¹ , A ³² and A ³³ are independently unsubstituted or substituted aryl, biphenyl, heteroaryl, heterocyclyl or cycloalkyl radicals and have the same or different meanings in the three ligands P(A ³¹ A ³² A ³³ ); and X ³¹ is CI, Br, I, PF ₆ , [PF ₃ (C ₂ F ₅ ) ₃ ], SbF ₆ , BF ₄ , BARF, CIO ₄ , CF ₃ SO ₃ , CH ₃ CO ₂ or CF ₃ CO ₂ . Process according to at least one of the preceding claims, characterized in that the rhodium complex is a complex of formula III-1: [(P(Phenyl) ₃ RhCl] III-1 procedure according to claim 3 , characterized in that the rhodium complex is formed in situ by reacting a rhodium complex precursor with the phosphine ligand or ligands. procedure according to claim 4 , characterized in that the rhodium complex precursor is selected from a complex of formula VI, VII or X: [(dien)RhX ⁶¹ ] ₂ VI [(dien) ₂ Rh]Y ⁷¹ VII RhX ¹⁰¹ _{3· xH2} OX wherein X ⁶¹ and X ¹⁰¹ independently represent Cl, Br or I; x is 0, 1, 2 or 3; Y ⁷¹ represents an anion of the formula PF ₆ , [PF ₃ (C ₂ F ₅ ) ₃ ], SbF ₆ , BF ₄ , BARF, ClO ₄ , CF ₃ SO ₃ , CH ₃ CO ₂ or CF ₃ CO ₂ ; and diene is 1,5-cyclooctadienyl (COD), norbornadienyl, (ethylene) ₂ or (cyclooctene) ₂ and the phosphine ligand(s) is/are selected from compounds of formula XI and/or XII: P(A ¹¹¹ A ¹¹² A ¹¹³ ) XI

wherein A ¹¹¹ , A ¹¹² , A ¹¹³ , A ¹²¹ , A ¹²² , A ¹²³ and A ¹²⁴ independently represent unsubstituted or substituted aryl, biphenyl, heteroaryl, heterocyclyl or cycloalkyl radicals; and G is an alkylene bridge having 1 to 8 carbon atoms or is unsubstituted or substituted 1,2-phenylene, 2,3-naphthylene, 2,2'-biphenylene or 1,1'-di(cyclopentadienyl)iron. Method according to at least one of Claims 4 or 5 , characterized in that the rhodium complex precursor is a complex of formula VI-1: [(COD)RhCl] ₂ VI-1 and the phosphine ligand(s) is triphenylphosphine or tri(ortho-tolyl)phosphine. A composition comprising a compound of formula IIA or IIB

where f, g, h, i and j, A ²¹ , A ²² , A ²³ , A ²⁴ , A ²⁵ , R ²¹ , W, Y ²¹ , Z ²¹ , Z 23 , Z ²⁴ and Z ²⁵ and ^{Z 22 as} in claim 1 are defined; and a rhodium complex stabilized with one or more identical or different phosphine ligands.