WO2006125529A1 - Formyltetrahydropyrans, method for the production thereof and use thereof in the production of liquid crystal compounds - Google Patents

Abstract

The invention relates to formyltetrahydropyrans comprising mesogenic substituents, to a method for the production thereof and to the use thereof for producing substituted tetrahydropyran derivatives.

Description

FORMYLTETRAHYDROPYRANES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE IN THE PREPARATION OF LIQUID CRYSTALLINE COMPOUNDS

₅ The invention relates to formyltetrahydropyrans with mesogenic

Substituents, processes for their preparation and their use for the preparation of substituted tetrahydropyran derivatives.

Compounds having a _1Q tetrahydropyran ring as a key component of the molecule play an important role in organic chemistry, such as ingredients of natural or synthetic flavorants, drugs or mesogenic or liquid crystalline compounds, or as precursors for the synthesis of these substances ,

15

Liquid crystalline substances often have 1, 4-substituted

Cyclohexane rings within a rod-shaped structure. If these cyclohexane rings are replaced by arbitrarily oriented 2,5-substituted tetrahydropyran units, then, depending on the orientation of the

20 electronegative oxygen atom, resulting in beneficial changes in the overall physical properties of the molecule. In particular, an increase in the anisotropy of the electrical constants (Δε) can be achieved, both for positive (Δε> 0) and for negative dielectric compounds (Δε <0).

25 Examples of positive values of Δε are disclosed in EP 1482019 A1, likewise one finds an amplification of negative Δε values in compounds, as disclosed in EP 0967261 A1. Likewise, by reversely oriented tetrahydropyran units, a reduction in the absolute value of Δε is conceivable.

30

A gain of the positive Δε is z. B. for use in

IPS type liquid crystal displays (IPS = in beta switching), one Enhancement of the negative Δε in liquid crystal displays of the VA (VA = Yertical alignment) advantageous.

Linear 4-substituted (kalimitic or halm- or rod-shaped) formylcyclohexanes are valuable intermediates for the preparation of liquid-crystalline products with cyclohexane rings. The formyl group is characterized by its versatile reactivity, especially for chain extension for the construction of carbon skeletons and for the production of acetal structures. Thus, with the aid of the formylcyclohexanes using Wittig reactions (for example EP 0122389 A2, DE 3509170 A1, WO 95/30723 A1) or by condensation with 1,3-dihydroxy compounds (for example EP 0433836 A2, US Pat. DE 3306960 A1) highly refined, liquid-crystalline or mesogenic end products are produced.

It has now been found that formyl derivatives are also valuable intermediates for the derivatization of tetrahydropyran rings. In DE 3306960 A1, partial structures of the formula Ia are described.

However, the disclosed approach (Example 14) is multi-step and provided with labile (half) acetal intermediates, resulting in poor and unreproducible yields. In addition, no substances with formyl group in position 2 and another substituent in position 5 are disclosed therein. To date, only one compound of formula Ib has been found in the literature in P. Kocienski et al. (Synthesis (1991),

11, 1029-38).

DE 3306960 A1 discloses considerations that aldehydes can be prepared by oxidation from alcohols or by reduction from carboxylic acids, but does not disclose any embodiments.

It has also been found that certain dihydropyran compounds are useful as starting materials for the preparation of formyl tetrahydropyrans, of which only a few are known. A (2S) -2- (4-fluorophenoxy-methyl) -3,4-dihydro-2H-pyran is described by M.K. Gurjar et al. (Synthesis (2000), 4, 557-60), a 3- (2-benzyloxy-ethyl) -3,4-dihydro-2H-pyran from AP. Kozikowski et al. (J. Chem. Soc. Chem. Commun. (1980),

11, 477-9) to name the known representatives, which are linear

Own structure. Simple 2-alkyl or 3-alkyl derivatives of 3,4-dihydro-

2H-pyrans are also described without reference to liquid crystals. Are known z. B. previously alkyl (s) substituted dihydropyrans from C. Fehr et al., HeIv. Chim. Acta (1981) 65, 1247-56.

It was also the task of access to linearly substituted

To expand formyltetrahydropyrans with variable orientation of the pyran ring and to provide methods for their synthesis. The formed aldehydes integrate into existing and new syntheses for the preparation of 2,5-disubstituted tetrahydropyran compounds whose

End products z. B. can serve as mesogenic or liquid crystalline compounds.

The object has been achieved by processes for the preparation of formyl tetrahydropyrans of the formula II - A -

« ¹ + A ^L Z ^L tf -A ² -Z ² -yA ³ -Z ³ 4A ^l -CHO

where in the formula Il

A ⁴ stands for or

a, b, c are independently 0 or 1, where a + b + c is 0, 1, 2 or 3;

A ¹ , A ² , A ^{3 are} independently, the same or different, also rotated or mirrored, for

wherein optionally one to two carbon atoms through

N are replaced,

stand; and

Y ^1, Y ² and Y ³ are independently hydrogen, halogen, CN, NCS, SF _5, Ci- ₆ alkanyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, OCR ₆ - alkanyl, OC ₂ - ₆ Alkenyl and OC ₂ - ₆ alkynyl, wherein the aliphatic radicals are unsubstituted or monosubstituted or polysubstituted by halogen; and

Z \ Z ² , Z ^{3 is} a single bond, an unsubstituted or mono- or polysubstituted with F and / or Cl alkylene bridge having 1 to 6 carbon atoms, -CH ₂ O-, -OCH ₂ -, - (CO) O-, -0 (CO) -, -CF ₂ O-, -OCF ₂ -, -CH ₂ CH ₂ CF ₂ O- or -OCF ₂ CH ₂ CH ₂ -, n is 0, 1, 2, 3 or 4; n2 and n3 are independently 0, 1, 2 or 3; n4 is O, 1 or 2; W ^{1 is} -CH ₂ -, -CF ₂ - or -O-, R ^{1 is} H, halogen, CN, NCS, SF ₅ , CF ₃ , OCF ₃ , NH ₂ , a boronic ester, an unsubstituted or simply CN or simply or alkyl group having 1 to 15 carbon atoms substituted several times by halogen, where in these radicals also one or more CH ₂ groups are each independently denoted by -C≡C-, -CH =CH-, -O-, -S- , -SO-, -SO ₂ -, -O (CO) - or - (CO) O- may be replaced so that

Heteroatoms in the chain are not directly linked, and

which is characterized in that a) hydroformylating a compound of the formulas IIIa, IIIb and / or IIIc,

R ¹ -fA ¹ -z ¹ tfA ² -Z ² -MA ³ -Z ³ -t INc or b) a compound of formula IV

R z -Z -Z ^ -R ³ IV

by one or more reactions of IV, the at least one

Reduction step include, implemented

R ^{3 is} CN, COOH, CONHR ⁴ , COOR ⁴ and R ^{4 is} an alkyl, aralkyl or (optionally substituted) aryl, or c) an alcohol of the formula V

oxidized to aldehydes according to formula II, wherein in the formulas Illa-c, IV and V

A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c and R ^{1 have} the meanings given for formula II.

The process according to the invention makes available the tetrahydropyran-aldehydes of the formula II with the aid of readily available and inexpensive reagents in a simple manner, good yields and high chemo- and stereoselectivity starting from intermediates of the formulas IIIa-c, IV or V. The aldehydes are useful intermediates for the synthesis of many different compounds that are used as liquid crystalline substances, alone or in mixtures. The aldehydes may also be prepared, isolated, purified or used as hydrates, as an adduct with sulfite or in the form of their acetals. The invention therefore also includes aldehydes of the formula II, where the compounds of the formulas

and

not included. Preferred compounds are mentioned below or correspond to the preferences associated with one or more of the processes for the preparation or one or more of the uses of compounds of formula II.

Preference is given to the preparation of compounds of the formula II which are characterized in that, independently of one another,

A ⁴ for - () - stands,

R ^{1 is} F, OCF ₃ , CF ₃ , OCF ₂ H, SF ₅ , A ¹ and A ² are each independently 1, 4-phenylene, 2,5-difluoro-1, 4-phenylene or 2-fluoro-1 , 4-phenylene, a, b are 1, c is O, and / or

Z ^{1 is} a single bond, -CF ₂ O-, -OCF ₂ -, - (CF ₂ ) ₂ -, -CH ₂ CF ₂ -, -CF ₂ CH ₂ -, -CH ₂ CH ₂ CF ₂ O- or -OCF ₂ CH ₂ CH ₂ - is.

Likewise preferred is the preparation of compounds of formula II, which are characterized in that

R ^{1 is} F, Cl, Br, a boronic acid ester or an unsubstituted or monosubstituted or mono- or polysubstituted by halogen alkyl group having 1 to 15 carbon atoms, wherein in these radicals also one or more CH ₂ groups each independently of one another can be replaced by -C≡C-, -CH = CH-, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) -, that heteroatoms in the chain are not directly linked together, and A ¹ , A ² and A ^{3 are} 1,4-phenylene, 2,3-difluoro-1, 4-phenylene, 2-fluoro-1, 4-phenylene or 3 -Fluoro-1, 4-phenylene and a, b and c are independently O or 1.

Very particular preference is given to the preparation of compounds of the formulas A-G

OHC-) O-alkyl F

wherein X ^{2 is} F or OCF ₃ and g is O, 1 or 2 and alkyl is as defined later

Corresponding to the preferred preparation processes, suitable starting materials according to variants a), b) and c) are used.

In the first embodiment (a) of the present invention, the tetrahydropyran-aldehydes II are produced from the dihydropyrans according to the formulas Illa-c. In the preferred embodiment of (a) the conversion to the aldehyde takes place in a hydroformylation reaction, preferably a catalytic hydroformylation using a gas mixture of hydrogen and carbon monoxide. In an alternative embodiment, a silane hydrogen is used instead of hydrogen, wherein the silyl enol ethers formed are readily transformable into the corresponding aldehydes. In a preferred embodiment, transition metal catalysts suitable for the hydroformylation, in particular those of the transition metals rhodium (Rh), ruthenium (Ru) or cobalt (Co) are used. The metal nuclei of the catalysts can be equipped with various ligands at the central atom of the transition metal, so with CO

(Brennstoffchemie (1966), 47, 207), phosphines (J. Organomet. Chem. (1977), 124, 85), phosphine oxides (J. Chem. Soc. Chem. Commun. (1994), 115; J. Organomet. Chem. (1995), 488, C20-C22) and phosphites (J. Organomet. Chem. (1991), 421, 121; ibid (1993), 451, C15-C17). Particularly preferred catalysts are cobalt compounds with carbonyl ligands or rhodium compounds with phosphorus ligands. The catalysts may also be generated in situ in the reaction mixture by adding a suitable commercial (precursor) salt, e.g. A Rh (I) salt (see Catalog Strem No. 20, Strem Chemicals Inc., Kehl, Germany), such as Rh (I) acac (CO) ₂ (acac = acetylacetonate), Rh (I) acac (COD ) (COD = 1, 5-cyclooctadiene), [RhCI (COD)] ₂ or [RhCI (CO) ₂ ] ₂ with the corresponding ligands, in the case of these salts z. B. with 2 to 10 times the molar amount of triphenylphosphine or tris (ortho-t-butylphenyl) phosphite is added. The specific embodiments known from the literature (Angew. Chemie (1993), 105, 1588) of the two-phase or multiphase catalysis (supported aqueous phase = SAP) can also be applied to the hydroformylation reaction. So can Dihydropyrane the

Formulas Illa-c with hydrophilic substituents such as OH, NH ₂ , COOH, SO ₃ H in the aqueous / organic two-phase system in the presence of HRh (CO) (tppts) ₃ (tppts = Triphenylphosphintris-m-sulfonic acid sodium salt), be hydroformylated. The hydroformylation of lipophilic educts of the formulas IIIa-c can, for. B. are advantageously carried out with the so-called SAP catalysts, which consist of a granular, porous support material with a large inner surface on which the catalyst complex is distributed by adsorption or as a thin film. Such supported catalyst systems can preferably be prepared with HRh (CO) (tppts) ₃ or Co ₂ (CO) ₆ (tppts) ₂ and used for hydroformylation.

The process for the hydroformylation of the substrates II is particularly characterized in that the catalysis is carried out with transition metal complexes of the metals rhodium or cobalt, which consist of cobalt compounds with carbonyl groups or rhodium compounds with phosphorus ligands. The compounds IIIa and IIIc are hydroformylated with high regioselectivities to give the corresponding aldehydes of formula II when Dikobaltoctacarbonyl or Rh complexes with P ligands such as tris (ortho-tert-butylphenyl) phosphite or triphenylphosphine are used as catalysts. However, the leaves. Regioselectivity of the hydroformylation of the compounds IMb to the corresponding aldehydes Il to be desired. Even using relatively low temperatures (40 to 60 ^° C.) and low molar ligand ratios (2- to 4-fold phosphites or phosphines) on Rh catalysts, the regioisomers are obtained in a near 1: 1 ratio (A. Polo et al ., J. Chem. Soc, Chem. Commun. 1990, 600). Therefore, the hydroformylation of the derivatives purple or NIc, in particular purple, is preferred.

In a second embodiment (b) of the present invention, the tetrahydropyran-aldehydes II are prepared from the carboxylic acid derivatives IV, it being possible to use as reactants particularly free carboxylic acids, carboxylic esters, amides or nitriles or other compounds having a carbon atom of the same oxidation state ( + Il I) at this position. Particularly preferred are processes of this embodiment, the reactants of the nitrile type and

Alkyl esters, especially compounds of formula III with R ^{3 is} CN or -C (O) OAalkyl, wherein alkyl is in turn particularly methyl, ethyl isopropyl, t-butyl and benzyl groups. In a preferred embodiment of (b), the compounds of the formula IV are reduced by means of reducing metals, metal hydrides, metal alkyls or lower-valent boron compounds which avoid a further reduction of the aldehyde to the alcohol, more preferably of metal and / or borohydrides, the further alkyl , Amino, halogen or alkoxy groups. In a particularly preferred embodiment, the process uses diisobutylaluminum hydride (DIBAL-H) for reduction to the aldehyde, as described, for example, in E. Winterfeldt in Synthesis (1975), 9, 617-630 and the references cited therein, or other dialkylaluminum hydrides or amino- or alkoxy-substituted lithium aluminum hydrides such as LiAlH (NH ₂ ) 2 and LiAlH (Ot-Bu) ₃ . The methods are known in principle and can be found as examples and citations in standard works such as J. March, Advanced Organic Chemistry, 4th Ed, Wiley, New York (1992).

In a third embodiment (c), the alcohol compounds according to formula V are oxidized by means of oxidizing reagents to aldehydes according to formula IV. In preferred embodiments of this process, the oxidations are carried out by oxidation methods which avoid too extensive oxidation to the carboxylic acid or carboxylate, in particular by means of Crθ ₃ or chromate (VI) (especially pyridinium chromates), organo-iodine reagents of Type of periodinane (Dess-Martin oxidation), DMSO / DCC (Pfitzner-Moffatt oxidation), DMSO / oxalyl dichloride (Swern oxidation), acetone / Al (OAlkyl) ₃ (Oppenauer oxidation) or NaOCl (catalyzed with 2,2,6 Use 6- tetramethylpiperidine N-oxide (TEMPO) or with transition metal catalysts). Representative of the known technical literature, the following references are given for the reaction types mentioned:

Crθ ₃ oxidation: (a) JC Sauer in Organic Synthesis, John Wiley Sons, New York (1963), Coli. Vol. 4, 813; b) GR Rasmusson et al., ibid. (1973), Coli. VoI 5, 324; c) RW Ratcliffe; ibid. (1988), Coli. Vol. 6, 373; d) JC Collins, WW Hess, ibid. (1988), Coli. Vol. 6, 644; e) B. Khadilkar et al., Synth. Commun. (1996), 26, 205.

Dess Martin oxidation: a) DB Dess, JC Martin, J. Org. Chem. (1983), 48, 4155; J. Amer. Chem. Soc. (1991), 113, 7277 b) A. Speicher et al., J. prakt. Chem. (1996), 338, 588. Pfitzner-Moffatt oxidation: JG Moffat in oxidation ", Vol. 2, RL Augustine and DJ Trecker - Ed Marcel Dekker, New York, 1971, 1-64 (with DMSO / DCC). Swern oxidation: a) AK Sharma, D. Swern, Tetrahedron Lett. (1974)

1503; b) D. Swern et al., J. Org. Chem. (1976) 41, 3329; c) P. Kocieński, R.

Whitby, Synthesis (1991), 1029.

Oppenauer Oxidation: C. Djerassi in Organic Reactions, John Wiley Sons, New York (1951), Vol. 6, 207.

NaOCl oxidation, Ru or TEMPO-catalyzed: a) RJ. Crawford, J. Org.

Chem. (1983), 48, 1367b) P.L Anelli et al., Org. Synth. (1990) 69, 212.

A reference to 2-formyltetrahydropyrans has the Kocieήski et al. described Swern oxidation of a corresponding carbinol.

The alcohol compounds V are generally prepared by standard methods from the nitriles and carboxylic acid derivatives of the formula IV by reduction. Powerful reducing agents such as LiAIH _{4 are} suitable for this purpose.

Another object of the present invention is the preparation of 2- or 3-substituted dihydropyran compounds according to the formulas Illa-c, in particular of UIb and IIIc, which can be prepared in a surprisingly simple manner from corresponding homoallylic alcohols via intermediates (Schemes 1-3 ).

The novel compounds of formula IIIb and IIIc are part of the invention. Known 2-substituted dihydropyrans have hitherto been alkyl (s) substituted dihydropyrans from C. Fehr et al., HeIv. Chim. Acta (1981) 65, 1247-56, and a compound of the formula

from MK Gurjar et al., Synthesis (2000), 4, 557-60, which were made without reference to liquid crystalline compounds. Known 3-substituted dihydropyrans are previously alkyl-substituted dihydropyrans from z. BP Kocienski et al., J. Chem. Soc. Perkin Trans. (1985), 1879-84. The compounds of the formula INb and IHc according to the invention

are characterized in that if a, b, c are simultaneously 0, then

R ^{1 is} halogen, CN, NCS ₁ SF ₅ , CF ₃ , OCF ₃ , NH ₂ , an alkyl group having 1 to 15 C atoms which is monosubstituted or monosubstituted or polysubstituted by halogen, where one or more CH ₂ Each independently of one another by -C≡C-, -CH = CH-, -O-, -S-, -SO-,

-SO ₂ -, -COO- or -OCO- can be replaced so that heteroatoms are not directly linked in the chain; and if for IMb a = 1 and b + c = O and A ¹ is 1, 4-phenylene, then Z ^{1 is} not -OCH ₂ - or -CH ₂ CH ₂ -. A is 1, 2 or 3. In the case where a is O, R ¹ preferably represents a mono- or polysubstituted fluorine-substituted alkyl group having 1 to 15 C atoms, where in these radicals also one or more CH ₂ - Groups each independently of one another by -C≡C, -CH = CH-, -O-, -S-, -SO-, -SO ₂ -, -COO- or -OCO- may be replaced so that heteroatoms in the Chain are not directly linked.

In a first embodiment of the preparation of the dihydropyran compounds of the formulas IIIa-c, 1-substituted homoallylic alcohols are allylated on the free OH group and the open-chain diene compounds are prepared by ring-closing olefinic metathesis with elimination of one molecule of ethylene to give 2-substituted 3,6 Dihydro-2H-pyrans reacted. In a preferred embodiment according to Scheme 1, the 2- substituted dihydropyrans HIa in a synthesis process from homoallylic alcohols of the formula VI by an O-allylation to the intermediate VII. In the second reaction step VII is converted by a ring-closing metathesis to VIII. The olefinic ring closure metathesis is preferably carried out by ruthenium-methylidene catalysts

Carbene or phosphine ligands (eg, by various "Grubbs catalysts" according to Grubbs et al.), Or new improved variants.

The allylation of VI takes place z. Example, under micellar catalysis with an allyl halide in the presence of Cetyltrimethylammoniumbromid in

Tetrahydrofuran and a little water (B. Jursic et al., Tetrahedron (1988), 44, 6677).

VII

^IIIa

Scheme 1. Preparation of 2-subst. 3,6-dihydro-2H-pyran via metathesis.

In a second embodiment of the reaction procedure, generally 1-substituted homoallylic alcohols are subjected to a hydroformylation and then or simultaneously to a hemiacetal ring closure. The resulting OH-substituted tetrahydropyrans provide by elimination of the OH group together with an adjacent proton in Advantageously, the required 2-substituted 3,6-dihydro-2H-pyran derivatives. In a preferred embodiment, use is made of homoallylic alcohols of the formula VI which, according to Scheme 2, after hydroformylation, hemiacetal formation and elimination of the resulting OH group give the 2-substituted variants of the dihydropyrans Hlb. The elimination of the OH group is carried out as water or after transformation into a leaving group, particularly preferably by conversion into a methanesulfonic acid ester or into a p-toluenesulfonic acid ester.

VI

OH

In the B

Scheme 2. Preparation of 2-subst. 3,4-dihydro-2H-pyran according to Wuts.

The two reaction steps shown in Scheme 2 can be carried out sequentially or in a combined reaction sequence. The

Hydroformylation follows in principle literature methods, in

Special one to Wuts et al. (Tetrahedron Lett. (1984), 25, 4051-4) based on laboratory synthesis. The rhodium catalyst rhodium acetate dimer used gives good selectivity and is easy to handle. In principle, instead of the readily available rhodium acetate, other commercially available rhodium catalysts or known from the literature organometallic cobalt catalysts, in particular cobalt carbonyls are used.

In a third embodiment of the preparation of dihydropyrans, 2-substituted homoallylic alcohols of the formula XII are subjected to a hydroformylation and a ring closure to give compounds of the formula XIII. Subsequent elimination of the OH group on XIII gives the 3-substituted-3,4-dihydro-2H-pyran of the formula INc (Scheme 3).

XII

XIII

IIIc

Scheme 3. Preparation of 3-subst. 3,4-dihydro-2H-pyran.

For the hydroformylation with simultaneous ring closure, the same remarks apply as for the 2-substituted substrate VI according to Scheme ₂ .

The elimination of the OH group in the compounds X and XIII to the elimination products IHb or IHc is achieved by elimination analogous to Boeckman et al. (J. Am. Chem. Soc. (1991), 113, 5337-53, Scheme 3). For example, the OH group with

Mesyl chloride and triethylamine mesylated and immediately thereafter eliminated slight heating. Also suitable is p-toluenesulfonic acid chloride to produce a leaving group.

Particular preference is given to processes for the preparation of compounds of the formula II from compounds of the formulas NIb or NIc. They are characterized in that the compounds of the formulas NIb or NIc can be prepared from compounds of the following formulas X and XIII,

in that the hydroxyl group is eliminated directly or after conversion into a leaving group, wherein A ¹ , A ² , A ³ , Z ¹ , Z ² , Z ³ , a, b, c and R ^{1 have} the meaning as for formula II.

In a preferred procedure, the compounds of the

Formula X and XIII from compounds of formulas VI and XII

produced by a hydroformylation step and a ring closure, wherein

A ¹ , A ² , A ³ , Z \ Z ² , Z ³ , a, b, c and R ^{1 have} the meaning as for formula II. The homoallylic alcohols of the formulas VI and XII are either known in the art, are commercially available or can be readily prepared by synthesis methods which are known per se from the literature. Scheme 4 represents the synthesis of a 1-substituted homoallylic alcohol from aldehydes. In this synthesis, for example, an AIIyI Grignard reagent is reacted with an aldehyde. The aldehydes are in turn known compounds or may, for. B. can be obtained by a process according to the invention ajar method.

IX Scheme 4. Preparation of 1-substituted homoallylic alcohols.

In Scheme 5, a synthetic route for the 2-substituted variants of

Homoallyl alcohols, starting from an allyl halide derivative of the formula XVI, outlined:

XVII

XII Scheme 5. Preparation of 2-substituted homoallylic alcohols.

Starting from XVI, for example starting from the aldehyde

R ¹ - [A ¹ -Z ¹ ] a - [A ² -Z ² ] _b - [A ³ -Z ³ ] _c -CΗO _z . B. by Reformatski synthesis to the unsaturated ester R ¹ - [A ¹ -Z ¹ ] a- [A ² -Z ² ] _b - [A ³ -Z ³ ] c-CH = CH-CO ₂ alkanyl, followed by reduction with DIBAL-H to the corresponding allyl alcohol R ¹ - [A ¹ -Z ¹ ] _a - [A ² -Z ² ] _b - [A ³ -Z ³ ] _c -CH = CH-CH ₂ OH and final halogenation with PBr ₃ (HaI = Br) ₁ PCI ₅ or SO ₂ Cl ₂ (HaI = Cl) or Hl (HaI = I) can be prepared, the compound XVII is obtained by reaction with a suitable metal or organometallic reagent; where "Met" is a function of the metallic or organometallic reagent used for Cu, Bi (ReSt) ₂ , In (ReSt) ₂ , Sn (ReSt) ₃ , Sn (radical), Zn (radical), Ge (radical), wherein "radical" represents one or more organic radicals, ligands or counterions on said metal. The further reaction of XVII, which can also take place without prior isolation of the intermediately formed XVII, with formaldehyde (or a synthesis equivalent) yields, after appropriate work-up, the desired homoallylic alcohol of the formula XII. Further access to homoallylic alcohols of the formula XII is carried out according to Scheme 6; "HaI" has the same meaning as in Scheme 5 above; "Met" is preferably Cu (see A. Carpita, R. Rossi, Synthesis (1982), 469):

R '+ A A A Ha,

XVIII

^R '+ ^ALz 4if ^A2 - ^z2 -tf ^A3 - ^z3 - I ₇ MOt

XIX

\

XX

XII

Scheme 6. Alternative preparation of 2-substituted homoallylic alcohols.

The halide XVIII is - according to the procedure in Scheme 4 - transferred with a suitable reagent in the organometallic derivative XIX, which is then reacted with XX to Homoallylacetat XXI. From XXI is then obtained by saponification of the desired homoallylic alcohol of the formula XII.

Furthermore, homoallylic alcohols of the formula XII in which R ¹ - [A ¹ -Z ¹ ] a - [A ² -Z ² ] _b - [A ³ -Z ³ ] c is an alkyl radical are also by appropriate alkylation with an alkyl halide R ¹ - [A ¹ -Z ¹ ] _a - [A ² -Z ² ] _b - [A ³ -Z ³ ] _c -halo of the dianion of crotonic acid and subsequent reduction accessible with LiAlH ₄ . This dianion is from crotonic acid z. Obtained by reaction with 2 equivalents of lithium diisopropylamide (LDA) (see PE Pepper, LS Silbert, J. Org. Chem. (1971), 36, 3290; RH van der Veen, H. Cerfountain, J. Org. Chem. (1985), 50, 342).

The synthesis of the carboxylic acid derivatives according to formula IV for the reduction to the aldehyde is carried out as outlined by the general examples in Schemes 7 and 8. MES stands for a mesogenic radical R ¹ - [A ¹ -Z ¹ ] _a - [A ² -Z ² ] _b - [A ³ -Z ³ ] _c - as in formula IV. Instead of the ester group, the radicals R ³ substituents indicated in formula IV. In both examples, the compounds of formula IV (represented by representative example compounds XXIV and XXVII) are obtained by ring-closing metathesis from appropriately substituted precursors of formulas XXII or XXV and by subsequent hydrogenation of the metathesis product. The precursors of the formulas XXII and XXV are obtained as described in EP 1482019 A1 for such or analogous diene compounds. Alternatively, compounds of formula XXII are obtained by alkylating an allyl alcohol HO-CH (MES) -CH ₂ CH = CH ₂ with a corresponding acrylate compound.

XXII XXIII

XXIV

Scheme 7. Preparation of compounds of formula XXIV as a variant of the preparation of compounds of general formula IV.

XXV XXVI

XXVII

Scheme 8. Preparation of compounds of formula XXVII as a variant of the preparation of compounds of general formula IV.

The cyano-substituted representatives of formula IV (R ³ = CN) are z. B. indirectly via the dihydropyrane INc accessible. These can be chlorinated in analogy to the chlorination of the unsubstituted 5,6-dihydro-4H-pyran with gaseous hydrochloric acid and then either with AgCN (BA Nelson et al., J. Org. Chem. (1956), 21, 798) or by means of trimethylsilyl cyanide in the presence of SnCl ₂ (Reetz, M. et al., Tetrahedron (1983), 33, 961) to cyano compounds of formula IV.

Preference is thus given, inter alia, to those processes for preparing tetrahydropyran-aldehydes of the formula II which are characterized in that compounds of the formula IV which are intended for reduction to compounds of the formula II are prepared from dihydropyran derivatives by means of hydrogenation, which again from suitably substituted dienes by means of catalytic ring-closing metathesis with release of ethylene.

The tetrahydropyran-aldehydes of the formula II can be used to prepare further mesogenic or liquid-crystalline tetrahydropyran derivatives. Preference is given to the use of the aldehyde compounds II for the synthesis of addition or condensation products the aldehyde group for the construction of partial elements of mesogenic structures. The aldehyde group is particularly preferably used for the construction of 5- to 6-membered ring systems, very particularly for the construction of a further tetrahydropyran ring or a 1,3-dioxane ring.

Accordingly, a preferred use of the aldehydes of the formula II is characterized in that the reaction takes place with 1, 3-diols to dioxanes. This is done according to methods known per se, as described in the literature (eg in standard works of synthetic organic chemistry such as Houben-Weyl, Methods of Organic

Chemistry, Georg Thieme Verlag, Stuttgart). The 1,3-diols are preferably substituted at position 2 with simple substituents such as R ¹ (defined according to formula II) or with mesogenic radicals. Particularly preferred is a substitution by a radical such as R ¹ or a radical -AR ¹ , where A is a cyclohexane-1, 4-diyl, a tetrahydropyran-2,5-diyl or a 1, 3-dioxane-2,5- Diyl stands.

A further preferred use of the aldehydes of the formula II is characterized in that the reaction takes place with allyl-metal compounds to Homoallylalkoholen as precursors to tetrahydropyrans. The resulting homoallyl compounds serve as starting material for the preparation of a further adjacent pyran ring according to the methods already described above (Schemes 1 and 2).

Likewise preferred is the use of the aldehyde group in the aldehyde compounds of the formula II for chain extension via a Wittig reaction, which leads to 1, 2-ethenylene bridges on tetrahydropyran. The use of the aldehyde compounds of formula II is therefore particularly characterized in that a compound of formula IX

is prepared via a Wittig reaction from the aldehyde Il, wherein

R ¹ , R ² , A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c have the meaning as for formula II and, in each case independently,

A ⁵ and A ⁶ as A ¹ ,

Z ⁵ and Z ^{6 are defined} as Z ¹ and _Q e and f are as a.

In a further preferred form of the use of compounds of the formula II, the aldehydes, via allylation of the carbonyl function, etherification of the alcohol with a propynyl radical and subsequent enyne metathesis, are a dihydropyran ring which is substituted by an optionally substituted ethenyl group (cf. EP 1482020 A1). The optional substituent depends on the optional substitution of the allyl-Grignard compound used for the allylation. The use of the aldehyde compounds according to formula II in this case is accordingly particularly characterized in that compounds of the formula Qa,

a (partially) saturated hydrogenation product of compounds of formula Qa or a synthetic precursor to Qa of formulas Qb or Qc

0

where Qa, Qb and Qc

R ¹ , R ² , A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c, have the meaning as for formula and each independently A ⁵ and A ⁶ as A ¹ , Z ⁵ and Z ^{6 are defined} as Z ¹ and e and f are as in formula II. A ⁴ in Qa, Qb and Qc is preferably a ring of the formula

Preference is given to the use of compounds of the formula II in the event that in the relevant formulas, independently of one another,

A ⁴ stands for

R ^{1 is} F, OCF ₃ , CF ₃ , OCF ₂ H, CN, SF ₅ ,

A ¹ and A ^{2 are} independently 1, 4-phenylene, 2,5-difluoro-1, 4-phenylene or 2-fluoro-1, 4-phenylene, a, b is 1, c is O, and Z ^{1 is} a single bond, -CF ₂ O-, -OCF ₂ -, - (CF ₂ ) ₂ -, -CH ₂ CF ₂ -, -CF ₂ CH ₂ -,

-CH ₂ CH ₂ CF ₂ O- or -OCF ₂ CH ₂ CH ₂ -.

Likewise preferred is the use of compounds of the formula II, which are characterized in that R ^{1 is} F, Cl, Br, a boronic acid ester or an unsubstituted or monosubstituted or mono- or polysubstituted by halogen alkyl group having 1 to 15 carbon atoms, wherein in these radicals also one or more CH ₂ groups each independently -C≡C-, -CH = CH-, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) - may be replaced by heteroatoms in the chain are not directly linked, and

A ¹ , A ² and A ^{3 are} 1,4-phenylene, 2,3-difluoro-1, 4-phenylene, 2-fluoro-1, 4-phenylene or 3-fluoro-1, 4-phenylene and a, b and c are independently O or 1.

Particularly preferred is the use of Tetrahydropyranaldehyden the following formulas A-G:

wherein X ^{2 is} F or OCF ₃ and alkyl is generally defined as described later. In particular, in the formulas AG alkyl is a straight-chain, saturated or unsaturated carbon chain having 1-8 C atoms.

From the said process according to the invention for the preparation of the aldehydes of the formula II and their uses, a total of a process for the preparation of 2,5-disubstituted tetrahydropyran derivatives, in particular the formula results

^Ri + ^ALz 4if ^ALz2 if ^ALZ 4Γ * ⁴ f ^{z5 "A5} -tf

comprising a) the preparation of a formyltetrahydropyran according to one or more of the preceding processes, and b) the use of formyltetrahydropyran for the preparation of a 2,5-disubstituted tetrahydropyran derivative according to one or more of the preceding embodiments of the invention, in which

R ¹ , R ² , A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c, have the meaning as for formula II and each independently

A ⁵ and A ⁶ such as A ¹ , Z ⁵ and Z ⁶ such as Z ¹ , f 0, 1 or 2, and e are as defined in a formula II. Depending on the procedure, the meanings of the variables are subject to the restrictions specified or directly apparent there.

Another use of aldehydes according to formula II is the

Derivatization as hydrate, sulfite adduct or the formation of acetals for

Purpose of the cleaning or as protection of the aldehyde during the

Cleaning, chemical conversion or storage.

A further aspect of the present invention are novel formyltetrahydropyrans of the formula II as defined above, which are preferably characterized in that, independently of one another, at least one of Z ¹ , Z ² , Z ³ in the molecule of a group -CF ₂ CF ₂ -, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CH ₂ CH ₂ CF ₂ O-, -OCF ₂ CH ₂ CH ₂ -, -CF ₂ O- or -OCF ₂ - corresponds to, or, that

R ¹ corresponds to NCS, SF ₅ , CF ₃ , OCF ₃ or OCHF ₂ , or that at least one of

A ¹ , A ² , A ³ or means.

Particularly preferred are aldehydes of the formulas IIa, IIb or Nc

in which

R ¹¹ and R ^{12 is} F, CF ₃ , OCF ₃ , CN, NCS, SF ₅ or a mono- or polysubstituted with halogen alkyl group having 1 to 15 carbon atoms, wherein in these radicals also one or more CH ₂ groups each independently of one another can be replaced by -C≡C-, -CH = CH-, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) -, that heteroatoms in the chain are not directly linked to one another, R ^{13 is defined} as R ¹ for formula II, L ¹ , L ² independently of one another are H, Cl or F, and A ¹ , A ² , Z ¹ , Z ² , a, b have the definition as in formula II.

Very particular preference is given to the formyltetrahydropyrans of the above formulas A, B, C, D, E, F and G.

In the context of the present invention, the term "alkyl", unless otherwise defined elsewhere in this specification or in the claims, means in its most general meaning a straight-chain or branched, saturated or unsaturated aliphatic hydrocarbon radical having 1 to 15 (ie 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms; this radical is unsubstituted or monosubstituted or polysubstituted by fluorine, chlorine, bromine, iodine, carboxy, nitro, NH ₂ , N (alkanyl) ₂ and / or cyano, the multiple substitution having the same or different substituents can be done. Also, the alkyl radical in the aliphatic hydrocarbon chain itself may be functionalized.

If this alkyl radical is a saturated radical, it is also referred to as "alkanyl". Furthermore, the term "alkyl" also includes unsubstituted or correspondingly in particular with F, Cl, Br, I and / or CN mono- or polysubstituted by identical or different substituents hydrocarbon radicals in which one or more CH ₂ groups are replaced by -O- ( "Alkoxy", "oxaalkyl"), -S- ("thioalkyl"), -SO ₂ -, -CH = CH- ("alkenyl"), -C≡C- ("alkynyl"), - (CO) O - or -0 (CO) - may be replaced, that heteroatoms (O, S) are not directly linked in the chain. 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, isobutyl, t-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl , CF ₃ , CHF ₂ , CH ₂ F, CF ₂ CF ₃ . 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 may 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 bonded directly to the group or substituted ring substituted by the alkoxy radical and alkyl is as defined above; preferably, alkyl is then alkanyl or alkenyl. preferred

Alkoxy radicals are methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy,

Heptoxy and octoxy, wherein each of these radicals may also be substituted, preferably with one or more fluorine atoms. Particularly preferred alkoxy is OCH ₃ , OC ₂ H ₅ , OnC ₃ H ₇ , OnC ₄ H ₉₎ OtC ₄ H ₉ , OCF ₃ ,

OCHF ₂ , OCHF or OCHFCHF ₂ . In connection with the present

Invention means the term "oxaalkyl" alkyl radicals in which at least one non-terminal CH ₂ group has been replaced by -O- that there are no adjacent heteroatoms (O, S). Preferably, oxaalkyl straight-chain radicals includes the formula Ca H2a ₊ RO- (CH ₂₎ b-, where a and b are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; more preferably a is an integer from 1 to 6 and b is 1 or 2.

If one or more CH ₂ groups have been replaced by sulfur in an alkyl radical as defined above, a "thioalkyl" radical is present. "Thioalkyl" preferably comprises a straight-chain radical of the formula C _a H2a ₊ iS- (CH ₂ ) b-, where a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 and b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; more preferably a is an integer from 1 to 6 and b is 0, 1 or 2. The thioalkyl radical may also be substituted with 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 may also be referred to as "alkadienyl". An alkenyl radical may contain 2 to 15 (ie 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms and is branched chain or preferably straight chain. The rest is unsubstituted or monosubstituted or polysubstituted, identically or differently, in particular with F, Cl, Br, I and / or CN, ie one or both hydrogens of the -CH = CH unit and / or one or more hydrogens of the further CH ₂ or CH ₃ groups of the alkenyl radical can be replaced by the substituent (s). Furthermore, one or more CH ₂ groups can each independently of one another by -O- ("alkenyloxy"), -S-, -C≡C-, -CO-, - (CO) O-, -O (CO) - so be replaced, that heteroatoms (O, S) are not directly connected to each other. if the

CH = CH group on both carbon atoms a radical other than

Hydrogen carries, say, if it is a non-terminal group, the

CH = CH group exist in two configurations, namely as E-isomer and as a Z-isomer. The same applies to the substituted with halogen and / or -CN C = C double bond groups. In general, the E isomer (trans) is preferred. Preferably, the alkenyl radical contains 2, 3, 4, 5, 6 or 7 carbon atoms and is vinyl, allyl, 1E-propenyl, 2-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, allyl, 1E-propenyl, 2-propenyl and 3E-butenyl.

If one or more CH ₂ groups in an alkyl radical have been replaced by -C≡C-, an alkynyl radical is present. Also, the replacement of one or more CH ₂ groups by - (CO) O- or -0 (CO) - is possible. 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- (ethoxycarbonyl) propyl or 4- (methoxycarbonyl) butyl.

If, in an alkyl radical, a CH ₂ group is substituted by unsubstituted or substituted -CH = CH- and an adjacent CH ₂ group by CO,

- (CO) O- or -0 (CO) - are replaced, this radical may be straight-chain or branched. It is preferably straight-chain and has 4 to 12 C atoms. It therefore particularly preferably means acryloyloxymethyl,

2-acryloyloxyethyl, 3-acryloyloxypropyl, 4-acryloyloxybutyl, 5-acryloyloxy-pentyl, 6-acryloyloxyhexyl, 7-acryloyloxyheptyl, 8-acryloyloxyoctyl,

9-acryloyloxynonyl, methacryloyloxymethyl, 2-methacryloyloxyethyl, 3-methacryloyloxypropyl, 4-methacryloyloxybutyl, 5-methacryloyloxypentyl, 6-methacryloyloxyhexyl, 7-methacryloyloxyheptyl or 8-methacrylyloxyoctyl.

If the alkyl radical, alkanyl radical, alkenyl radical or alkoxy radical is substituted by at least one halogen, this radical is preferably straight-chain. Halogen is preferably F or Cl. In the case of multiple substitution, halogen is preferably F. The resulting radicals also include perfluorinated radicals. For single substitution, the fluoro or chloro substituent may be in any position, but preferably in the ω position.

In the context of the present invention, "alkylene" or "alkylene bridge" - unless the terms are different

In this description or in the claims are defined differently - for a divalent aliphatic hydrocarbon radical with 1, 2, 3,

4, 5, 6, 7, 8 carbon atoms in the chain, which may optionally also be mono- or polysubstituted by halogen, CN, carboxy, nitro, alkanyl, alkoxy, - NH ₂ or substituted with -N (alkanyl) ₂ , wherein the

Multiple substitution with the same or with different ones

Substituents can be made. Preferably, "alkylene" or

"Alkylene bridge" for a straight-chain, unsubstituted or fluorine mono- or di-substituted, saturated aliphatic radical having 1, 2, 3, 4, 5, 6 carbon atoms, in particular -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ - .

- (CHz) ₄ -, -CF ₂ CF ₂ - and - (CF ₂ J ₄ -.

In the context of the present invention, the term "aralkyl" refers to an aryl-alkyl radical, ie a radical in which an aryl substituent is linked via an alkyl bridge to an atom, a chain, another radical or a functional group , The alkyl bridge is preferably a saturated bivalent hydrocarbon radical ("alkylene"), 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 via an oxygen atom bound to the alkyl bridge with another atom, a chain, another radical or a functional group. Preferred examples of an aralkyl-O radical are O-benzyl and O-CH ₂ CH ₂ phenyl.

"Halogen" in the context of the present invention for fluorine, chlorine, bromine or iodine.

_Q .. In the context of the present invention, a "acetal" (also referred to as "hemiacetal") the product of (formal) addition of one equivalent of an alcohol (e.g. ethanol) to the carbonyl group of an aldehyde or of two equivalents of an alcohol (or two alcohols) to the carbonyl function of an aldehyde to understand. One

1 _c "Hydrate" of an aldehyde is in the context of the present invention, the product of a (formal) addition of one equivalent of water to the carbonyl function of an aldehyde (also referred to as "semi" or "semihydrate") or of two equivalents of water to the To understand the carbonyl function of an aldehyde. It is too

2 _Q note that an aldehyde with a corresponding acetal (and

Halbacetal) or with its hydrate (and semihydrate) may also be in equilibrium.

A boronic acid ester according to the invention is a radical of the formula -B (OAlkyl) ₂ , P ₅ where the two alkyls may also be replaced by an alkylene bridge or another divalent hydrocarbon radical.

If radicals or substituents of the compounds used _{according to} the invention or the _3Q compounds used _{according to} the invention are themselves optically active or stereoisomeric radicals,

Substituents or compounds may be present, for example, because they have an asymmetric center, so these are of of the present invention. It is understood that these compounds in isomerically pure form, for example as pure enantiomers, diastereomers, E or Z isomers, trans or cis isomers, or as a mixture of several isomers in any ratio, for example as a racemate, E - / Z

Isomer mixture or as a cis / trans isomer mixture, may be present.

Protective groups may be used to protect optionally functional groups or substituents which may be present in the compounds used in the process according to the invention from undesired reactions in the reaction according to the invention and / or preceding or subsequent reaction and / or work-up steps, which cleavage again after the reaction has ended can be. Methods for using suitable protecting groups are known to those skilled in the art and described, for example, in T.W. Green, P.G.M. Wuts: Protective Groups in Organic Synthesis, 3rd ed., John Wiley & Sons (1999).

The present invention will be further illustrated by the following examples without being limited to them.

Above and below, percentages are by weight. All

Temperatures are given in degrees Celsius. Tg is the glass transition temperature and KIp. is the clearing point. Furthermore, K = crystalline state, N = nematic phase, Sm = smectic phase and I

= isotropic phase. The information between these symbols represents the

Transition temperatures. Δn means optical anisotropy (589 nm,

20 ⁰ C), Δε the dielectric anisotropy (1 kHz, 20 ⁰ C) and γi the rotational viscosity at 20 ⁰ C [mPas].

The Δn and Δε values of the compounds according to the invention are determined by

Extrapolation obtained from liquid crystalline mixtures containing 10% of the respective compound of the invention and 90% of the commercially available liquid crystal ZLI 4792 (Merck, Darmstadt).

The following abbreviations are used above and below:

RT room temperature

DMSO dimethyl sulfoxide

DCC dicyclohexylcarbodiimide

TEMPO 2,2,6,6-tetramethylpiperidine N-oxide

DIBAL-H Diisobutylaluminum hydride

Examples

example 1

R = C ₃ H ₇ , m = O: (4b)

0.35 mol (84.8 g) of the diolefin (1) are in bulk at 40 ⁰ C under a nitrogen atmosphere in portions with 30 mg (0.035 mmol) of tricyclohexylphosphine (1, 3-bis (2,4,6-trimethylphenyl) 4,5-dihydroimidazol-2-ylidene-benzylidene-ruthenium (IV) chloride as metathesis catalyst (Grubbs 2 catalyst), the first portion being 20 mg and the second portion of 10 mg added after one hour The ethylene evolution virtually ended Filtration on silica gel with toluene / heptane (1 A) 61, 3 g (81, 7% of theory) of (2), which is used directly in the hydroformylation reaction to (3).

For this purpose, 0.25 mol (53.55 g) (2) in 200 ml of toluene at 60 bar and 150 ⁰ C with 3 g of tris (triphenylphosphine) carbonylrhodium (l) hydride until the consummate

Synthesis gas (H ₂ / CO = 1: 1) hydroformylated within 24 h. The reaction product is freed from the solvent by evaporation in vacuo and the residue is filtered through silica gel with toluene / ethyl acetate (9: 1). The evaporation residue of the filtrate (37.2 g = 69.5% of theory) is subjected to a basic isomerization in order to concentrate the trans portion of the substituent arrangement in the formyl tetrahydropyran fraction.

For this purpose, the 37.2 g of the mixture in 190 ml of methanol and 48 ml of tetrahydrofuran with 1, 8 ml of 20% aqueous sodium hydroxide solution and stirred at room temperature for one hour. It is then neutralized with hydrochloric acid and the solution is concentrated to the residue. The evaporation residue is mixed with one liter of methyl tert-butyl ether and washed twice with 300 ml of water. After drying, the organic extract is evaporated, yielding 33 g of an 88% aldehyde mixture which, in addition to the trans-5-formyltetrahydropyran (3), still contains some 4-formyltetrahydropyran.

For the synthesis of (4a), 33 g (0.135 mol) of (3) with 27.1 g (0.135 mol) of 2- (4-trans-Propylcyclohexyl) -1, 3-propanediol in 250 ml of toluene with 500 mg of toluene-4 Sulfuric acid monohydrate heated until complete separation of water on a water separator under reflux for 2 h.

After cooling, 10 g of potassium carbonate are added with stirring, filtered and the filtrate evaporated to the residue. The evaporation residue is filtered through silica gel first with heptane / toluene (1: 1), then with pure toluene.

Two product fractions are obtained. From the one, by recrystallization, 12.4 g of the desired linear all-trans isomer (4a) (21, 4% of theory), from the other 5 g of the derived from 4-formyltetrahydropyran Fehlisomeren dioxane derivative.

(4a): K 106 N 206.9 I; Δε = 21, 7; Δn = 0.0871

Example 2

Analogously to Example 1, (4b) is obtained:

(4b): K 87 I; Δε = 23.7; Δn = 0.0550

Example 3

Analogously to Example 1, (4c)

(4c)

(4c): K 88 N (87.9) I; Δε = 35.8; Δn = 0.0880

Example 4

(8th)

0.2 mol (48.8 g) (3) are dissolved in 200 ml of tetrahydrofuran and mixed between 15 to 25 ⁰ C with 100 ml of 2-molar allyl magnesium chloride solution in tetrahydrofuran within 30 min dropwise. After completion of the addition, stirring is continued for 2 h at room temperature, then poured into 200 ml of 0.5 N hydrochloric acid, the organic phase separated and the aqueous phase extracted twice with methyl tert-butyl ether. The combined organic extracts are washed with water, dried and evaporated. The evaporation residue is filtered through silica gel with toluene / ethyl acetate (98: 2 to 9: 1). The filtrates yield 38.7 g (67.6% of theory) of an isomer mixture of homoallylic alcohols (5).

0.135 mole (38.7 g) of (5) and 0.135 mole (16.1 g) of propargyl bromide are dissolved in 80 ml of tetrahydrofuran and made into a vigorously stirred emulsion of sodium hydroxide pellets (0.27 mole, 10.8 g), 0.5 ml of water, 40 ml of tetrahydrofuran and 6.75 mmol (2.46 g) of N-cetyl-N, N, N-trimethyl ammonium bromide, heated to 45 ⁰ C and stirred for 16 h at this temperature. Then ice water is poured onto 1.5 l, the organic phase is separated off and the aqueous phase is extracted three times with MTB ether. The residue of the combined organic phases is, after prior drying and evaporation, filtered through silica gel with toluene / heptane 2: 8. After evaporation of the filtrate 34.3 g (78.4% of theory) (6) are obtained, which is used as a crude mixture directly in the enyne metathesis to (7). 0.028 mol (9.4 g) (6) are added in 20 ml of dichloromethane with 115 mg (0.14 m mol) of bis (tricyclohexylphospin) benzylidenruthenium (IV) chloride (Grubbs 1 catalyst) and stirred for 4 h at room temperature, whereupon the same portion of 115 mg of the catalyst is added again and stirred for a further 16 h at room temperature. After evaporation and filtration on silica gel with toluene / heptane (3: 7) and re-condensation of the obtained by evaporation of the filtrate residue (1, 0 g) first from ethanol, then from heptane, 0.6 g of an isomer are obtained, the Structure (7) is assigned.

(7): K 97 I; Δε = 14.2; Δn = 0.0800

0.2 g (7) are hydrogenated in 5 ml of methanol and 1 ml of toluene with 0.1 g of tris (triphenylphosphine) rhodium (l) chloride at 10 bar hydrogen pressure and 90 ⁰ C for 6 h. After cooling, the reaction mixture is evaporated in vacuo and filtered through silica gel with toluene / heptane (3: 7). After evaporation, 0.15 g (8) of oil is obtained.

Example 5

O) (10) [Rh] / H ₂

( ^4c )

The compound (9) is shown from the corresponding

Homoallylic Alcohol Precursor by O-Alkylation with Ethyl-2 (Bromomethyl) acrylate. For this purpose, 0.2 mol (8.0 g) of sodium hydride are added dropwise as a 60% suspension in 80 ml of tetrahydrofuran with stirring and external cooling with ice water with 0.2 mol (76.1 g) Homoallylalkohol in 80 ml of tetrahydrofuran under a nitrogen blanket, wherein the temperature is maintained at 20 ⁰ C. After about 2 hours is the

Hydrogen evolution finished. Then 0.2 mol (38.6 g) of the bromomethyl acrylate in 40 ml of tetrahydrofuran are added dropwise so that the temperature does not exceed 25 ⁰ C. The mixture is then further stirred at room temperature for 16 h. Then, the reaction mixture is poured onto 600 ml of ice water, neutralized with 1 N HCl and the organic phase separated. After extracting the aqueous phase twice with methyl tert-butyl ether, the combined organic phases are evaporated after drying and filtered through silica gel with toluene / methyl tert-butyl ether (3: 1). The evaporation residue of the filtrate contains 65.9 g (71% of theory) of the alkylation product (9).

0.1 mol (49.2 g) (9) are heated to 60 ° C. with 25 ml of toluene and admixed with 4 portions of 212 mg Grubbs 2 catalyst (total 1 mol%) at intervals of one hour. After completion of the ethylene development, the reaction mixture is filtered through silica gel with toluene / methyl tert-butyl ether. After evaporation of the filtrate remain 28.8 g (62% of theory) of Dihydropyranesters (10).

0.05 mol (23.2 g) Dihydropyranester (10) are hydrogenated in 300 ml of methanol and 60 ml of toluene at 10 bar hydrogen pressure and 100 ° C for 12 h with 2 g of tris (triphenylphosphine) rhodium (l) chloride. The hydrogenated ester (11) is obtained after evaporation of the solvent and filtration of the residue over silica gel with toluene / methyl tert-butyl ether (18.4 g = 79% of theory).

For the synthesis of the aldehyde (12) 0.039 mol cooled (18.4 g) ester (11) in 80 ml of toluene at -70 ⁰ C and treated with 32.5 ml of 1, 2-N-Diisobutylalumi- aluminum hydride (DIBAL-H) in toluene at -70 ° C with stirring and 4 h after completion of the addition and continued stirring still cold poured into 100 ml of cold 1 N HCl. The organic phase is washed with aqueous sodium bicarbonate solution and water, dried and evaporated. The evaporation residue of the aldehyde (12) can be used directly for the synthesis of (4c), as described in Example 1.

Example 6

Analogously to Example 5, the synthesis of (13) is also possible.

(13)

Example 7

Analogously to Example 5, the synthesis of (14), this time with the aldehyde (3) succeeds.

(14)

(14): K 91 SmH (63) N 203.4 I; Δε = 21, 3; Δn = 0.0880

Example 8

The acid (15), prepared by alkylation of the sodium salt of methallyl alcohol with the sodium salt of bromoacetic acid (16 h in tetrahydrofuran at 60 ⁰ C) in the presence of dicyclohexylcarbodiimide (DCCI), as dehydrating agent and 4-dimethylaminopyridine (DAP) in dichloromethane (16 h, room temperature) with allyl alcohol to the ester (16). This is rearranged according to Claisen-Ireland by means of lithium diisopropylamide in the presence of chlorotrimethylsilane to (17) (addition at -75 ° C, then 16 h room temperature, solvent tetrahydrofuran). (17) is esterified with 3,4,5-trifluorophenol in the presence of DCCI and DAP to give (18). Ring closure to Dihydropyranester (19) is carried out by heating in bulk to 80 ⁰ C under N ₂ protective gas and addition of 0.5 mol% Grubbs-2 catalyst, wherein after 15 minutes of foaming by the ethylene still held at 80 ⁰ C for 5 minutes becomes. After filtration through silica gel with toluene, the (in 65% of theory) isolated Dihydropyranester (19) (11 g) with Wilkinson's catalyst (2 mol%) tris (thphenylphosphine) rhodium (l) chloride in 60 ml of ethyl methyl ketone and 60 ml of toluene at 100 ⁰ C and 11 bar for 17 h to Tetrahydropyranester (20) hydrogenated. 0.05 mol (13.7 g) (20) are reduced with DIBAL-H to the aldehyde (21) as described in Example 3 for the reduction of the ester (1 1) to the aldehyde (12).

Example 9

Analogously to Example 8, the aldehyde (23) is prepared from the ester (22).

DIBAL-H

(22) (23)

Example 10

(24) (25) (26)

(28) (27)

(29) (30)

(31) The synthesis of the dihydropyranyl ester (27) via the allylation of the homoallylic alcohol and the ring-closing metathesis of (26) is carried out analogously to that of the dihydropyranyl ester (10) from Example 3. 51 g of the ester (27) are hydrogenated in 600 ml of n-heptane with 12 g of Pd / C (5%) at 10 bar hydrogen pressure and 23 ⁰ C within 9 h to the isomer of Tetrahydropyranester (28).

0.074 mol (21 g) of the isomeric esters (28) are refluxed with 0.081 mol (4.55 g) of KOH in 200 ml of methanol under nitrogen for 6 h and stirred for a further 12 h at room temperature. Then the solvent is largely removed, the residue treated with 90 ml of 1 N HCl, filtered off and washed with water. The residue is treated with toluene and evaporated again for azeotropic drying. In alkaline saponification, a large proportion of the cis-ester or the cis- acid is isomerized to give the trans-derivative. There remain 17 g (90% of theory) of

Tetrahydropyranic acid (29).

0.067 mol (17 g) of acid (29) are added dropwise in 90 ml of tetrahydrofuran to a mixture of 0.05 mol (1, 91 g) of LiAlH ₄ in 10 ml of tetrahydrofuran such that only a gentle reflux occurs. After completion of the addition is heated for 6 h at reflux. You let it cool and move with it

75 ml of cooled 2N HCl with stirring. After separating the two

Phases, the aqueous phase is still twice with 100 ml

Extracted methyl tert-butyl ether. The combined organic phases are washed neutral with 50 ml of saturated NaHCO ₃ solution and water, dried and evaporated. There are obtained 12.3 g (76.4% of theory) of alcohol (30).

The alcohol (30) is oxidized to the aldehyde (31) according to Swern. To do this

0.0635 mol (4.95 g) of dimethyl sulfoxide in 60 ml of dichloromethane at -60 ⁰ C while stirring with 0.0525 mol (12.5 g) of trifluoroacetic anhydride in 15 ml of dichloromethane within 5 minutes to give the temperature of -60 ⁰ C given. After completion of the addition and further stirring for 10 minutes at -60 ⁰ C 0.05 mole (12.0 g) of the alcohol are added dropwise (30) in 40 ml dichloromethane with stirring, during ca. minute 5- dropping, and 10 min then the temperature to -60 ⁰ C is held. Then allowed to warm to room temperature and added dropwise 18.5 ml of triethylamine within 10 minutes in such a way that the temperature does not rise above 30 ⁰ C under temporary external cooling. After completion of the addition is left for 30 min at room temperature, then the reaction mixture washed with 100 ml of water. The aqueous phase is extracted with 50 ml of dichloromethane. The combined organic phases give after drying and evaporation 6.4 g (54% of theory) of the aldehyde (31).

Example 11

(32) (33) (34)

(36) (35)

H ₂ [Rh]

(37)

The dihydropyran (32) generated by metathesis is converted by hydroformylation to the aldehyde (33) analogously to Example 1 and is first reacted with the homoallylic alcohol (34) in an ene-carbonyl reaction to give the bromotetrahydropyran (35). The homoallylic alcohol is synthesized via the acetate of the zinc alcohol (38) which can be prepared by conventional methods by reaction with gaseous formaldehyde in the presence of zinc dust and CoBr ₂ .

(38)

In a solution of 26 g of zinc dust (0.4 mol), 13.2 g (0.06 mol) of CoBr ₂ and 0.2 mol (51, 2 g) (38) in 400 ml of acetonitrile by heating 1, 0 mol (30 g) of paraformaldehyde to 220 ⁰ C in an extra piston formed gaseous formaldehyde, after the zinc has been activated with 1 ml of trifluoroacetic acid. After the completed introduction is stirred for a further 12 h at room temperature. Thereafter, it is poured onto 100 ml of 2N HCl, the organic phase is separated off and the aqueous phase is extracted twice with methyl tert-butyl ether. The combined organic phases are evaporated, the remaining residue is filtered through silica gel with toluene / ethyl acetate (7: 3) and the more polar fraction is evaporated. The homoallylic alcohol (34) is obtained as raw material in a yield of 48% of theory. (21, 9 g).

0.09 mol (20.5 g) of Homoallylalkohols (34) are used together with

0.69 mol (14.0 g) aldehyde (33) and 5 mol% BiBr ₃ (2 g) at 0 ⁰ C submitted. Then HBr is introduced as a gas under external cooling at a temperature between 5-20 ⁰ until gas bubbles are discharged from the bubble counter located behind the reaction vessel, such as from the wash bottle located in front of the reaction vessel (about 10 minutes). It is then poured rapidly onto ice-cold, saturated sodium bicarbonate solution, the organic phase is washed with water, dried and evaporated. The isomer mixture of the isomeric bromotetrahydropyrans (35) is used crude in the next reaction stage, in the HBr cleavage to produce the dihydropyran (36).

0.057 mol of isomer mixture (36) from the precursor (23.3 g, 63.3% of theory) are mixed with 0.086 mol (10.2 ml) of 1, 5-diazabicyclo [4,3,0] non-5- in 40 ml Toluene heated at reflux for 6 h. After cooling, it is adjusted to pH 3 with water and dilute sulfuric acid and vigorously mixed. After separation, the organic phase is washed with saturated NaHCO ₃ solution and water and filtered through silica gel. After evaporation, 15.7 g (84% of theory) of an isomer mixture of dihydropyrans (36) are obtained.

The hydrogenation of the isomer mixture (36) (15.7 g) is carried out by dissolving in 300 ml of methanol and 75 ml of toluene and 20 hours of hydrogenation at 10 bar, 90 ° C by means of 0.48 mmol (448 mg) of tris (triphenylphosphine) rhodium (I) chloride as a catalyst. After evaporation of the solvent, the residue is filtered through silica gel with toluene. Multiple fractionated crystallizations from ethanol and heptane give 0.5 g (37).

Example 12

(39) (40)

Under nitrogen, a solution of 272 g (800 mmol) of the aldehyde in 500 ml of THF with 800 ml of a 1 M solution of allylmagnesium bromide in diethyl ether at a temperature below 25 ⁰ C added. The batch is stirred at RT overnight, added to ice-water and then extracted with methyl tert-butyl ether. The organic phase is washed with saturated NaCl solution, dried over sodium sulfate and concentrated. The residue obtained is passed through silica gel.

103 g (81%, 220 mmol) of the alcohol and 21 g (80 mmol) of triphenylphosphine are dissolved in 500 ml of ethyl acetate and admixed with 500 mg of rhodium acetate dimer. The hydroformylation is carried out at 25 bar synthesis gas and 100 ⁰ C. The reaction solution is concentrated and passed through silica gel.

Under nitrogen, a solution of 100 g (240 mmol) of the lactol and 101 ml (299 mmol) of triethylamine in 500 ml of dichloromethane at 0-5 ° C with 24.5 ml (320 mmol) of methanesulfonyl chloride. The mixture is stirred overnight at room temperature. The batch is added to water and extracted with methyl tert-butyl ether. The organic phase is washed with saturated NaCl solution, dried over sodium sulfate and concentrated. The residue obtained is passed through silica gel.

60 g (148 mmol) of the enol ether are dissolved in 300 ml of toluene and treated with 9.8 g (15 mmol) of tris (2,4-di-tert-butylphenyl) phosphite and 390 mg (1, 5 mmol) of dicarbonylacetylacetonate rhodium (l) offset. The hydroformylation is carried out bar of synthesis gas and 100 ⁰ C at the 100th The solution is then concentrated and the residue is passed through silica gel. A cis / trans mixture of the aldehyde is obtained.

The signals of the aldehyde protons are δ = 9.69 ppm and δ = 9.88 ppm.

The aldehyde (43) is then reacted with 2-ethyl-1, 3-propanediol to dioxane (4c) (see Example 3). To this are dissolved 44.5 g (110 mmol) of the aldehyde (43) and 12.0 g (115 mmol) of the diol 2-ethyl-1,3-propanediol in 250 ml of toluene, 400 mg of p-toluenesulfonic acid monohydrate and until heated to complete conversion of the aldehyde (DC) under reflux at the water. The cooled batch is washed three times with sat. Washed sodium bicarbonate solution, concentrated and passed through silica gel (toluene / heptane 7: 3, toluene, toluene / ethyl acetate 95: 5). The product-containing fractions are concentrated and the residue recrystallized at -2O ⁰ C from ethanol.

(4c): K 88 N (87.9) I; Δε = 35.8; Δn = 0.0880 Example 13

9.0 g (0.038 mmol) of 3- (4'-pentylcyclohexyl) -2H-3,4-dihydropyrane (44) are dissolved in 100 ml of toluene with 0.4 g of dicobaltoctacarbonyl under 1.7 l of synthesis gas (H ₂ / CO = 1: 1) reacted at 140 ⁰ C / 300 bar for 2 h. After cooling, the reaction solution is evaporated and the residue with heptane / toluene (1: 1) filtered through silica gel. The filtrate after evaporation gives 9.1 g of a light brown oily residue in which the ratio of alcohol (46) to aldehyde (45) is 4: 1. This mixture is used directly for the oxidation to the aldehyde (45) (see also oxidation step according to Swern in Example 10).

Claims

claims

1. A process for the preparation of formyl-tetrahydropyran derivatives of the formula II

where in the formula Il

A ⁴ stands for or

a, b, c are independently 0 or 1, where a + b + c is 0, 1, 2 or 3;

A ¹ , A ² , A ^{3 are} independently, the same or different, also rotated or mirrored, for

wherein optionally one to two carbon atoms through

N are replaced,

stand;

Y ¹ , Y ² and Y ^{3 are} independently hydrogen, halogen,

CN, NCS, SF _5, de-alkanyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, Od ₆ - alkanyl, OC _2-6 alkenyl, and OC ₂ - mean ₆ alkynyl, wherein the aliphatic radicals unsubstituted or monosubstituted or polysubstituted by halogen; and

Z ¹ , Z ² , Z ^{3 is} a single bond, an unsubstituted or mono- or polysubstituted with F and / or Cl alkylene bridge having 1 to 6 carbon atoms, -CH ₂ O-, -OCH ₂ -, - (CO) O-, - 0 is (CO) -, -CF ₂ O-, -OCF ₂ -, -CH ₂ CH ₂ CF ₂ O- or - CF ₂ OCH ₂ CH ₂ -, n is 0, 1, 2, 3 or 4; n2 and n3 are independently 0, 1, 2 or 3; n4 is O, 1 or 2;

W ^{1 is} -CH ₂ -, -CF ₂ - or -O-;

R ^{1 is} H, halogen, CN, NCS, SF ₅ , CF ₃ , OCF ₃ , NH ₂

Boronic acid ester, an unsubstituted or monosubstituted or mono- or polysubstituted by halogen alkyl group having 1 to 15 carbon atoms, wherein in these radicals also one or more CH ₂ groups each independently of one another by -C≡C-, -CH = CH, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) - may be replaced so that heteroatoms in the chain are not directly linked; characterized in that a) hydroformylated a compound of the formulas IIIa, INb and / or IHc

or b) a compound of formula IV 0

^Ri + ^ALz Hif ^A - ^z2 iF ^A3 - ^z3 -fcA ⁴ -R ³ iv by one or more reactions of IV involving at least one reduction step, wherein

R ³ is CN, COOH, CONHR ^4, COOR ⁴ and R ⁴ is an alkyl, aralkyl or ¹ S

(optionally substituted) aryl, or c) oxidizing an alcohol of the formula V,

R ¹ + A ¹ - ^Z 4d-A- ^z2 iK ^z3 4A ⁴ -CH ₂ OH V

wherein the formulas IIIa, INb, INc, IV and V ⁰ A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c and R ^{1 is} the same as for

Have formula Il.

2. The method according to claim 1, characterized in that the

Compounds of formulas IHb and / or NIc are prepared from compounds of the following formulas X or XIII,

XIII

by eliminating the hydroxyl group directly or after conversion into a leaving group, wherein A ¹ , A ² , A ³ , Z ¹ , Z ² , Z ³ , a, b, c and R ^{1 are} independently defined as for formula II in claim 1 ,

3. The method according to claim 1 or 2, characterized in that the compounds of formula X and XIII from compounds of formulas VI and XII

be prepared by a hydroformylation step and a ring closure, wherein

A ¹ , A ² , A ³ , Z ¹ , Z ² , Z ³ , a, b, c and R ^{1 have} the meaning as for formula II in

Claim 1 have.

4. The method according to claim 1, characterized in that the

Tetrahydropyran compounds of the formula IV are prepared from corresponding dihydropyran derivatives by means of hydrogenation, which in turn are prepared from appropriately substituted dienes by means of catalytic ring-closing metathesis with release of ethylene.

5. The method according to claim 1 or 4, characterized in that the reduction of the compounds of formula IV to aldehydes of the formula II by means of reducing metals, metal hydrides, metal alkyls or lower-valent boron compounds.

6. The method according to one or more of the preceding claims, characterized in that the reduction of the compound of formula IV with diisobutylaluminum hydride, dialkylaluminum hydrides or amino- or alkoxy-substituted lithium aluminum hydrides takes place.

7. The method according to one or more of the preceding claims, characterized in that the hydroformylation of the compounds of formulas IIIa, IMb or IHc catalytically with simultaneous use of carbon monoxide and hydrogen, or instead of hydrogen with hydrosilanes or formates with subsequent hydrolysis of the intermediates.

8. The method according to one or more of the preceding claims, characterized in that the hydroformylation of

Compounds of the formulas IIIa, IMb or INc are catalytically using transition metals.

9. The method according to one or more of the preceding claims, characterized in that the catalysis with

Transition metal complexes of the metals rhodium or cobalt is made, consisting of cobalt compounds with carbonyl ligands or rhodium compounds with phosphorus ligands.

10. The method according to one or more of the preceding claims, characterized in that the oxidation of the compounds of formula IV by methods, the CrO ₃ , iodine reagents Dess-Martin, DMSO / DCC (Pfitzner-Moffatt oxidation), DMSO / Oxalyldichlorid (Swem oxidation), acetone / Al (OAlkyl) ₃ (Oppenauer oxidation) or NaOCl, catalyzed with

2,2,6,6-tetramethylpiperidine N-oxide or transition metal catalysts.

11. Formyl-tetrahydropyran derivatives of the formula II according to claim 1, wherein the compounds of the formulas

and

■ are not included.

12. Formyltetrahydropyran derivatives of the formula II according to the preceding claim, characterized in that at least one of Z ¹ , Z ² , Z ³ in the molecule of a group -CF ₂ CF ₂ -, -CF ₂ CH ₂ -, - ₁ 5 CH ₂ CF ₂ -, -CH ₂ CH ₂ CF ₂ O-, -OCF ₂ CH ₂ CH ₂ -, -CF ₂ O- or -OCF ₂ -, or, that

R ¹ corresponds to NCS, SF ₅ , CF ₃ , OCF ₃ or OCHF ₂ , or that at least one of

²⁰ A ¹ , A ² , A ³ - / ^~ \ - or - ( ^~ \ - means.

13. Formyl-tetrahydropyran derivatives according to one or more of the preceding claims, characterized in that they are selected from the formulas IIa, IIb or Hc

30

in which

R ¹¹ and R ^{12 is} F, CF ₃ , OCF ₃ , CN, NCS, SF ₅ or a mono- or polysubstituted with halogen alkyl group having 1 to 15 carbon atoms, wherein in these radicals also _Q or more CH ₂ groups each independently of one another can be replaced by -C≡C-, -CH = CH-, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) - in that heteroatoms in the chain are not directly linked to one another and 5 R ^{13 is defined} as R ¹ in claim 1,

L ¹ , L ^{2 are} independently H, Cl or F, and

A ¹ , A ² , Z ¹ , Z ² , a, b have the definition as in claim 1 for formula II.

14. Compounds of the formula IHb and IHc

5 as defined in claim 1, characterized in that, when a, b and c are simultaneously O, then

R ^{1 is} halogen, CN, NCS, SF ₅ , CF ₃ , OCF ₃ , NH ₂ , an alkyl group which is monosubstituted by CN or mono- or polysubstituted by halogen

1 to 15 C atoms, wherein in these residues also one or more 0

CH ₂ groups each independently of one another by -C≡C-,

-CH = CH-, -O-, -S-, -SO-, -SO ₂ -, - (CO) O- or -O (CO) - to be replaced may show that heteroatoms in the chain are not directly linked; and when a = 1 and b + c = 0 and A ¹ is 1, 4-phenylene, then Z ^{1 is} other than -OCH ₂ - or -CH ₂ CH ₂ -.

15. Use of the aldehyde compounds of the formula II according to claim 1 for the synthesis of addition or condensation products of the aldehyde group.

16. Use according to claim 15, characterized in that the aldehyde group serves to build up an optionally substituted 5- to 6-membered ring.

17. Use according to claim 15 or 16, characterized in that the reaction with diols to dioxanes or with allyl metal

Compounds to Homoallylalkoholen and further to a second Tetrahydropyranring takes place.

18. Use according to claim 14, characterized in that a compound of formula IX

is prepared via a Wittig reaction from the aldehyde M, wherein

R ¹ , R ² , A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c have the meaning as for formula II in claim 1 and each independently A ⁵ , A ⁶ such as A ¹ , Z ⁵ , Z ⁶ as Z ¹ and e, f as a are defined for formula II.

19. Use according to one or more of the preceding claims, characterized in that compounds of the formula Qa,

a (partially) saturated hydrogenation product of compounds of formula Qa or a synthetic precursor to Qa of formulas Qb or Qc

where Qa, Qb and Qc

R ¹ , R ² , A ¹ , A ² , A ³ , A ⁴ , Z ¹ , Z ² , Z ³ , a, b, c, the meaning as for formula

II in claim 1 and each independently

A ⁵ , A ⁶ as A ¹ ,

Z ⁵ , Z ⁶ such as Z ¹ and e, f are as defined in formula II.

20. Process for the preparation of 2,5-disubstituted

Tetrahydropyran derivatives comprising a) the preparation of a formyltetrahydropyran according to one or more of the preceding claims, and b) the use of the formyltetrahydropyran according to one or more of the preceding claims for the preparation of the 2,5-disubstituted tetrahydropyran derivative.